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1
The Endocrine System
2
Outline
• Types of Regulatory Molecules
• Endocrine Glands and Hormones
• Paracrine Regulation
• Hormones That Enter Cells
• Hormones That Do Not Enter Cells
• Posterior and Anterior Pituitary Gland
• Thyroid and Parathyroid Glands
• Adrenal Glands
• Other Endocrine Glands
3
SIGNALING AGENTS & FACTORS
Neurotransmitters
Peptides
Oxygen-based molecules, e.g., NO
Prostanoids
Hormones
Cytokines ( some are Chemokines)
Extracellular-matrix molecules
Nutrients & metabolites
Mechanical stimuli, e.g., fluid shear
Cell-surface glycoproteins
Hormones from endocrine
cells & organs are part of a
much larger picture of the
outside controls on cells
Heat, osmolarity, exogenous chemicals, etc
ENDOCRINE
4
Types of Regulatory Molecules
• Hormone – A regulatory chemical secreted into the
blood by an endocrine gland, or an organ
exhibiting endocrine function.
• Target Cells respond to hormone
– Neurohormone – A chemical messenger
secreted by neuron into the blood rather than
the synaptic cleft.
• Paracrine - regulatory molecules work without
being transmitted by the blood – not endocrine
• Pheromone - communication messengers
5
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Axon
Neurotransmitter
Endocrine gland
Paracrine
regulator
Receptor
proteins
Hormone
carried
by blood
Target cell
6
Endocrine Glands and Hormones
• Hormones secreted by the endocrine glands belong to four
chemical categories:
– Polypeptides - short chains of amino acids less than
100 amino acids (insulin & ADH)
– Glycoproteins- longer than100 A.A. with carbs (FSH
and LH)
– Amines - Amines – A.A. derived from tyrosine and
tryptophan – epinephrine and norepinephrine and
melatonin
– Steroids - lipids derived from cholesterol

sex steroids - testosterone, estadiol, progesterone,
and cortisol – secreted by testes, ovaries, placenta
and adrenal cortex

Corticosteroids - adrenal cortex cortisol and
aldosterone (regulates glucose and salt balance)
– All hormones can be categorized as lipophilic (fat
soluble) or hydrophilic (water soluble).
7
Endocrine Glands and Hormones
• Neural and endocrine interactions
– Endocrine system also interacts and cooperates
with the nervous system to regulate the activities
of the other organ systems of the body.
– Secretory activity of many endocrine glands
controlled by nervous system like

Adrenal medulla, posterior pituitary, and
pineal gland

major site for neural regulation is the brain’s
regulation of the anterior pituitary by the
hypothalmus
However many are not under neural control
8
Human Endocrine System
major glands
9
cvlAl
re
u
o
- - - - - - - diaphragm
Parathyroids
Adrenal
cortex
Thyroid
Pituitary
anterior
Pancreas
Gonads
ENDOCRINE ORGANS I
10
[ non-epithelial origin ]
cvlAl
re
uo
- - - - - - - diaphragm
Parathyroids
Adrenal cortex
Thyroid
Pituitary
anterior
Pancreas
Gonads
ENDOCRINE ORGANS II
[Pineal]
[Heart]
[Adrenal medulla]
[Kidney]
[Placenta]
Plus neuroendocrine cells
developed within mature
gut, airway, etc epithelia
[Pituitary, posterior & Brain]
[Adipose
tissue]
11
TYPICAL ENDOCRINE GLAND - Context
hormone
release
vessels
Clumps of endocrine cells
blood
control
Capillary diffusion
TARGET ORGAN
Target cells,
with receptors
for binding
12
transport3
4 5
Target cells’
response
6
Feedback
12
GLAND(S) WHERE CELL TYPES HORMONES SPECIAL
Thyroid Neck
Follicular cells
C cells
Thyronine
Calcitonin
Follicles
for storage
Parathyroid Neck Chief cells Parathormone
/PTH
Small
Adrenal
medulla
Over
kidney
Chromaffin
cells
Epinephrine
Norepinephrine
Nerve
fibers
Adrenal
cortex
Over
kidney
Zona glomerulosa
Zona fasciculata
Zona reticularis
Mineralocorticoids
Glucocorticoids
Sex steroids
Pineal Brain’s
center
Pinealocytes Melatonin Connected
for light
drive
Zones
ENDOCRINE ORGANS I
13
GLAND(S) WHERE CELL TYPES HORMONES SPECIAL
Pituitary
posterior
Axons of PV &
SO hypothal.
neurons
Oxytocin
Vasopressin
/ADH
Extension
of brain
Pancreas Left
upper
quad
Beta, Alpha,
Delta, PP cells
Insulin Glucagon
Somatostatin
Pancr Peptide
Gonads Pelvic/
Scrotal
Granulosa, Theca
Lutein, & Leydig
Sex steroids
Inhibin
Placenta Uterus Syncytiotrophoblast Female: for amplified
hormonal responses
Female:
cyclic
Pituitary
anterior
Below
brain
MTs STs GTs
THs CTs
Blood drains
hypothal.-
pituitary for
control
Prolactin GH
LH FSH TSH
ACTH
Below
brain
Islets
+Pituicytes
s
ENDOCRINE ORGANS II
14
Paracrine Regulation
• Signaling between cells - Local effect and
short-lived occurs in many organs
• Regulatory molecules
– cytokines - regulate different cells of the
immune system
– growth factors - promote growth and cell
division in specific organs – stimulate cell
division at target cells
15
Paracrine Regulation
• Prostaglandins – most diverse group of paracrine regulators
• participate in regulation of:
– immune system – inflammation, pain and fever
– reproductive system – reproductive function ovulation,
labor,
– digestive system – inhibit gastric secretions, incrfease
motility and fluid absorption
– respiratory system - blood vessels constriction and dilation
in lungs
– circulatory system - blood platelets in blood clotting
– urinary system - renal blood flow vasodilation increasing
urine excretion
• Prostaglandin synthesis inhibited by aspirin.
– nonsteroidal anti-inflammatory drug

Ibuprofen

Work to inhibit inflammation and pain by inhibiting
enzyme necessary to produce prostaglandins –
(cyclooxygenase -2)
16
Hormones That Enter Cells
• Lipophilic hormones pass through the target
cell’s plasma membrane and bind to
intracellular receptor proteins.
– hormone receptor complex then binds to
specific regions of DNA

activate genes and regulate target cells
17
Steroid Hormone Action
18
Hormones That Do Not Enter Cells
• Hormones that are too large or too polar to
cross plasma membranes include all of the
peptide and glycoprotein hormones, as well
as catecholamine hormones epinephrine
and norepinephrine.
– bind to receptor proteins located on the
outer surface of the plasma membrane

cyclic AMP second-messenger system
 IP3/CA++
second-messenger system
19
Action of Epinephrine on a Liver Cell
1. Epinephrine is lipophobic and
needs to bind to specific receptor
proteins on cell surface.
2. Acting through intermediary G
proteins the hormone bound
receptor activates the enzyme
adenenylyl cyclase which converts
ATP to cAMP
3. Cyclic AMP performs as a
2ndary messenger and activates
protein kinase-A an enzyme that
was previously inactive
4. Protein kinase–A
phosphorylates and activates the
enzyme phosphorylase which
catalyses the hydrolysis of glycogen
into glucose.
20
IP3/CA++
Second-Messenger System
1. The hormone epinephrine
binds to specific receptor
proteins on the cell surface.
2. Acting through G- proteins,
the hormone-bound receptor
activates the enzyme
phospholipase C, which converts
membrane phospholipids into
inositol triphosphate (IP3)
3. IP3 diffuses thru the cytoplasm
and binds to receptors on the
endoplasmic reticulum
4. The binding of IP3 to the
receptor stimulates the
endoplasmic reticulum to release
Ca++ into the cytoplasm
5. Some of the released Ca++ binds to the receptor protein called calmodulin
6. The Ca++/Calmodulin complex activates other intracellular proteins – producing the
horomone effects
21
Primary endocrine organs
• Hypothalamus and pituitary gland secrete hormones and
regulate other endocrine organs. They are the main
regulatory organs of the endocrine system.
22
Hypothalamus
• Located below the
thalamus and above
the pituitary gland
(=epiphysis)
• Regulates the
pituitary gland
secretions through
two different
mechanisms
23
Hypothalamus - neurohypophysis
• 1- Neurons, receiving
information from
receptors, fire APs
which travel down to
the post pituitary gland
and stimulate the
release of stored
neurohormones –
Oxytocin (OT) and anti-
diuretic hormone
(ADH)
24
Hormones of the posterior pituitary
Regulation Hormone Target organ Action Pathology
Reflex Oxytocin - Uterus (smooth
muscle)
- breast tubules
(smooth muscles)
-labor and delivery
- milk-let down
--
--
Reflex (osmoreceptor) ADH
(vasopressin)
- DCT in kidney
tubules
- promote H2O
reabsorption
- not enough: diabetes
insipidus
- too much: ↑ BP?
25
Hypothalamus – adenohypophysis
• 2- Upon stimulation, secretory
cells located in the
hypothalamus secrete
“releasing” hormones which
travel down a capillary bed
toward the anterior pituitary
gland (adenopituitary). Each
type of releasing hormones will
stimulate the secretion and
release of a pituitary hormone.
• Hormones which control the
secretion of other hormones are
tropic hormones (found in
hypothalamus and pituitary
gland
26Figure 6.5
Hormones of the hypothalamus and anterior
pituitary gland
27Figure 6.8
Anterior pituitary
Regulation Hormone Target organ Action Pathology
GHRH and GHIH Growth hormone (GH) Many cells
(bones..)
Stimulate cell
growth and
cell division
- not enough:
children 
pituitary dwarfism
too much:
gigantism
(children) –
acromegaly (adult)
PRH - PIH Prolactin (PL) Breast secretory
cells
- milk
secretion
--
TRH Thyroid stimulating
hormone (TSH)
Thyroid gland - promote
thyroid gland
secretion (T3
and T4)
- not enough:
hypothyroidism
(cretinism in
children)
- too much:
hyperthyroidism
CRH Adrenocorticotropic
hormone (ACTH)
Adrenal cortex (3
layers)
- stimulates
secretion of
adrenal cortex
- not enough:
Addison's disease
- too much:
Cushing syndrome
GnRH Gonadotropin
- Follicle stimulating
hormone (FSH)
- Luteinizing hormone
(LH)
Stimulate gamete
maturation
Stimulate
gonadal gland
secretion and
gamete
formation
- infertility
28
Figure 23-17
Same Individual with Acromegaly (evolution over 20
years)
29Figure 6.6
Mechanism of control
30
HYPOPHYSIS/ Pituitary gland
Pituitary stalk
Posterior lobe
Hypoth alamus
Anterior lobe
Dura
IIIrd Ve
Intermediatelobe
31
Pars nervosa
Infundibular
process
Pars intermedia
PITUITARY SUB-DIVISIONS
Hypothalamic
SO & PV nuclei
Hypothalamic
median
eminence
ADENOHYPOPHYSIS
Pars distalis
Pars tuberalis
NEUROHYPOPHYSIS
Infundibular stem
neural part of stalk
1
3
2
1
2
3
32
Unlike some other endocrine cells, those of
the anterior pituitary separate their supplying a
hormone from the detection of the need for the
hormone.
The sensitivity to need is performed by
hypothalamic neurons, which can coordinate
requirements for several hormones with drives,
and events outside the person.
Anterior-pituitary cells & hormones
The system also allows for control by inhibitory
factors, as well as + driving hormone-releasing
factors
33
HYPOTHALAMO-HYPOPHYSEAL Portal flow
Superior arteries
Portal drainage
Hypothalamus
Anterior lobe
capillaries
Dura
Hypothalamic
capillary bed
Neurosecretory neurons
Veins
1
2
3
4
5
A portal flow takes venous
blood drained from one organ
and uses it as a supply to
another organ, e.g., gut to liver
34
HYPOTHALAMO-HYPOPHYSEAL Portal flow
Superior arteries
Portal drainage
Hypothalamus
Anterior lobe
capillaries
Hypothalamic
capillary bed
Neurosecretory neurons
Veins
1
2
3
4
5
Portal flow carries factors
from hypothalamic neurons
to pituitary anterior-lobe cells
E.g.,TH-RF
from neuron
causes
Thyrotroph
to release
TSH
35
Superior arteries
Portal drainage
Hypothalamus
Anterior lobe
capillaries
Hypothalamic
capillary bed
Neurosecretory
neurons
Veins
1
2
3
4
5
Mammotrophs MTs
Somatotrophs STs
Gonadotrophs GTs
Thyrotrophs THs
Corticotrophs CTs
Blood drains hypothalamus-pituitary for control by RFs, etc
Prolactin PRL
Growth hormone GH
Luteinizing hormone LH
Follicle-stimulating
hormone FSH
Thyroid-stimulating
hormone TSH
Adrenocorticotrophic
hormone ACTH
Anterior-pituitary cells & hormones
36
Mammotrophs MTs
Somatotrophs STs
Gonadotrophs GTs
Thyrotrophs THs
Corticotrophs CTs
Blood drains hypothalamus-
pituitary for control by RFs, etc
Prolactin PRL
Growth hormone GH
Luteinizing hormone LH/ICSH
Follicle-stimulating hormone
FSH
Thyroid-stimulating hormone
TSH
Adrenocorticotrophic
hormone ACTH cleaved from
pro-opio-melanonocortin/ POMC
Anterior-pituitary cells & hormones
Acidophil
Basophil
37
Anterior-pituitary cells 2
Mammotrophs MTs
Somatotrophs STs
Gonadotrophs GTs
Thyrotrophs THs
Corticotrophs CTs
Prolactin PRL
Growth hormone GH
Luteinizing hormone LH
FSH
TSH
ACTH
Acidophil Basophil Chromophobe
Chromophobes stain weakly, in comparison to CHROMOPHILS -
Acidophils & Basophils
Folliculo-Stellate cells lie amongst the glandular
cells; doing what?
38
Anterior-pituitary cells 3
Corticotrophs CTs ACTH
but by selective enzymatic cleavage of a larger 32kDa
precursor - pro-opiomelanocortin, also made in the
hypothalamus and elsewhere, and there serving to
provide other hormones & neurotransmitters
Pro-opiomelanocortin
ACTH
Pro-ACTH β-LPH
β-Endorphin
β-
MSH
SP
simplified
POMC ~ Pro-opiomelanocortin
39
Anterior-pituitary cells 4
Selective enzymatic cleavage of the precursor - pro-
opiomelanocortin, provides other hormones & transmitters
ACT
H
β-Endorphin
Pro-opiomelanocortinSP
NT 1-76
β-LPHACTH
β-LPHACTH
γ-LPH
NT 1-49
JP
γ -MSH α-MSH β-MSH
elaborate
MSH ~ Melanocyte-stimulating hormone
NT ~ amino-terminal peptides
LPH ~ Lipotropic hormone
Pro-hormone convertase 1
Pro-hormone convertase 1
Pro−γ -MSH
Pro−γ -MSH
After Reudelhuber
TL. J Clin Invest
2003;111:1115-1116
40
NEUROHYPOPHYSIS
Pars nervosa
Hypothalamic SO & PV nuclei
Supraoptic & Paraventricular nuclei
Hypothalamus 1
2
3
Inferior arteries
Veins
Release of hormone is
separated from production
*
*
*
*
Neural stalk
Optic
chiasm
41
NEUROHYPOPHYSIS
Pars nervosa
Hypothalamic SO & PV nuclei
Supraoptic & Paraventricular nuclei
Hypothalamus 1
2
3
Inferior arteries
Veins
*
*
Neural stalk
Optic
chiasm
Note - the supraoptic nucleus is
above the optic nerve & chiasm, but
closer to the chiasm is the small
suprachiasmatic nucleus (relaying
the darkness stimulus indirectly to
the pineal gland).
42
NEUROHYPOPHYSIS
Pars nervosa axons, terminals,
pituicytes & capillaries
Hypothalamic SO & PV nucleiHypothalamus
Infundibular stem
neural part of stalk - axons & glia
1
2
3
Neurosecretory neurons producing
oxytocin & vasopressin/ADH
Inferior arteries
Veins
Release of hormone is
separated from production
* *
*
*
43
NEUROHYPOPHYSIS
Hypothalamic SO & PV nucleiHypothalamus
Neurosecretory neurons producing
oxytocin & vasopressin/ADH
Inferior arteries
Veins
Hormone travels down the
axon bound to the carrier
protein - neurophysin, from
which it is cleaved for release
*
*
44
SUCKLING REFLEX
Hypothalamic SO & PV neuron activation
Hypothalamus
*
BREAST
Myoepithelial-cell
contraction
Sensory response
Oxytocin release
Stimulus1
2
3
4
56
7 Milk ejectionVascular transfer
45
PITUITARY Mid-sagittal section of 1-m embryo
STOMODEUM
PHARYNGEAL ARCHES
PITUITARY
RATHKE’S POUCH
starting in oral ectoderm
BRAIN
I
II
46
PITUITARY DEVELOPMENT II
Neural-tube diencephalic ectoderm
Oral-pharyngeal lining ectoderm
IIIrd Ve
Rathke’s pouch
Pars tuberalis
Pars distalis
Pars intermedia
Pars nervosa
Infundibular stem
Hypothalamus
ADENOHYPOPHYSIS
NEUROHYPOPHYSIS
47
PITUITARY DEVELOPMENT II
Pars tuberalis
Pars distalis
Pars intermedia
Pars nervosa
Infundibular stem
Hypothalamus
Pars nervosa
Infundibular
process
Pars intermedia
Hypothalamic
SO & PV nuclei
Hypothalamic
median
eminence
ADENOHYPOPHYSIS
Pars distalis
Pars tuberalis
NEUROHYPOPHYSIS
Infundibular stem
neural part of stalk1
3
2
1
2
3
Cysts
Cysts in Pars intermedia - remnants
of Rathke’s pouch lumen?
Rathke’s pouch lumen
48
Pars nervosa/
Infundibular process
Pars intermedia
Hypothalamic
SO & PV nuclei
Hypothalamic
median eminence
ADENOHYPOPHYSIS
Pars distalis
Pars tuberalis
NEUROHYPOPHYSIS
Infundibular stem/
neural part of stalk1
3
2
1
2
3
Cysts
Cysts in Pars intermedia - remnants
of Rathke’s pouch lumen?
49
Posterior Pituitary Gland
• Pituitary gland hangs by a stalk from the
hypothalamus of the brain.
– anterior pituitary - appears glandular
– posterior pituitary - appears fibrous
• Neurons produce antidiuretic hormone
(ADH) and oxytocin.
– stored in, and released from, the posterior
pituitary gland in response to neural
stimulation from the hypothalamus
50
Effects of ADH
51
Anterior Pituitary Gland
• Develops from a pouch of epithelial tissue that pinches off the
roof of the embryo’s mouth.
– produces the hormones it secretes:

growth hormone (GH) stimulates muscles and bones to
grow

adrenocorticotropic hormone (ACTH) regulates glucose
homeostasis

thyroid-stimulating hormone (TSH) stimulates the
production of thyroxin by thyroid gland

luteinizing hormone (LH) ovulation and testosterone
production in testes

follicle-stimulating hormone (FSH) develops ovarian
follicle and sperm in males

prolactin (PRL) stimulates mammary glands to produce
milk

melanocyte-stimulating hormone (MSH) synthesis and
dispersion of melanin pigment
52
Major Pituitary Gland Hormones
53
Anterior Pituitary Gland
• Hypothalamic control of anterior pituitary
gland secretion
– Neurons in the hypothalamus secrete
releasing hormones and inhibiting
hormones into blood capillaries at the base
of the hypothalamus.

Each hormone delivered by
hypothalamohypophysial portal system
regulates secretion or inhibition of a
specific anterior pituitary hormone.
54
Neurons in the hypothalamus secretes hormones that are carried by short
blood vessels directly to the ant. Pituitary gland, where they either stimulate
or inhibit the secretions of the ant pituitary hormones
Cell body
Axons to
primary
capillaries
Primary
capillaries
Pituitary stalk
Posterior pituitary
Anterior pituitary
Secondary
capillaries
Portal
venules
55
Anterior Pituitary Gland
• Negative feedback inhibition acts to maintain
relatively constant levels of the target cell
hormone.
– Positive feedback cannot maintain
constancy of the internal environment.
56
Negative Feedback Inhibition
Hormones secreted by some endocrine glands feed back to inhibit
the secretion of hypothalamic releasing hormones and anterior
pituitary hormones
57
Thyroid and Parathyroid Glands
• Thyroid gland
– Shaped like a shield and lies just below the
Adam’s apple in the front of the neck.

Thyroxine helps set basal metabolic rate
by stimulating the rate of cell respiration.

In children, thyroid hormones also
promote growth and stimulate maturation
of the central nervous system.

unique function in amphibians -
metamorphosis from larvae into adults
58
Regulation of Thyroxine Secretion
59
Thyroid and Parathyroid Glands
• Parathyroid gland and calcium homeostasis
– four small glands attached to the thyroid

produces parathyroid hormone (PTH)

one of only two hormones in humans
that are absolutely essential for survival

stimulates osteoclasts in bone to
dissolve calcium phosphate crystals
and release Ca++
into the blood
60
Regulation of Blood Calcium Levels
61
Calcium Metabolism:
Figure 23-20: Calcium balance in the body
62Figure 19.20
63
THYROID GLAND
Follicular cells
simple cuboidal
epithelium
Colloid / Thyroglobulin
glycoprotein = PAS+
Follicles for storage
C cells/ Parafollicular cells
Capillaries
In the section, the follicles do not hold their spherical shape this
well, and the colloid displays knife chatters and variable staining
64
THYROID GLAND: Physiological variablity
Follicular cells high
cuboidal when very active;
squamous when inactive
Colloid / Thyroglobulin
less in active state,
excessive in goitre
Follicles - size
varies inversely with
activity
C cells/ Parafollicular
cells for calcitonin
Capillaries
65
GOLGI
Amino acids
Sugars
Iodine
Thyroglobulin
Endocytosis
Cleavage
Release of hormones
T3 & T4
Synthesis &
iodination of
thyroglobulin
THYROID FOLLICULAR CELL
TSH
66
Goiter
• Both hypo and hyperthyroidism can have
goiter as a symptom
• Goiter is a swelling of the neck due to
hypertrophy of the thyroid gland
• How can one explain that?
67
Goiter in hypothyroidism
• Most often due to a lack of dietary
iodine
• The thyroid hormone is unable to
synthesize a functional thyroid
hormone (T3 and T4)
• The person express symptoms of
hypothyroidism
• The nonfunctional T3/T4 cannot
promote a negative feedback on
TRH and TSH

 the hypotalamus and pituitary
gland increase their secretions 
the thyroid gland is stimulated to
secrete more T3 and T4 …
• In children, the lack of functional
T3/T4 result in cretinism, a form a
mental retardation
68
Goiter in hyperthyroidism
• The cells secreting TRH or TSH
on the hypothalamus and
pituitary gland (respectively)
have become abnormal and no
longer are sensitive to the
negative feedback  they
continue to secrete TRH or TSH
 continuous stimulation of the
thyroid gland with excess thyroid
hormones being formed

 symptoms of hyperthyroidism
69
PARATHYROID GLAND
Oxyphil cells
Chief cells
Characteristic is the
lack of obvious general
structural features
Small, pale, resemble
lymphocytes, but
have more cytoplasm
Larger, eosinophilic,
darker nuclei,
packed with
mitochondria
70
PARATHYROID GLAND
OXYPHIL CELLS
CHIEF CELLS
have membrane
calcium sensors to
respond to low Ca2+
by releasing
parathyroid
hormone /PTH. PTH
stimulates
osteoclasts to
release Ca2+
from
bone & has
conserving renal
effects
derivatives of Chief cells
71
Osteoclast
Ruffled border agitating
released enzymes & acid
Eaten-out hole is
a Howship’s
lacuna
BONE REMODELING
Osteoclasts as a team eating
out a resorption tunnel
Sealing ring
of tight
attachment
to bone
BONE
MATRIX
BONE
72
ONCOCYTIC CONVERSION
As cuboidal epithelia and glands age, a few of
their epithelial cells lose most of their normal
organelles and fill up with mitochondria.
Mitochondria-rich cells are eosinophilic.
This event results in two classes of cell:
those that are functioning normally and need
many mitochondria - gastric parietal cells, renal
proximal-tubular cells, striated-duct cells, etc; &
non-functional mitochondria-stuffed cells in older
epithelia. These have acquired two names: the
usual - oncocyte, and, as an exception, the
archaic oxyphil cell in the parathyroids. & Hurthle cells
in thyroid
:
73
Adrenal Glands
• Adrenal glands are located above each
kidney.
– Each gland composed of inner portion
(adrenal medulla) and outer layer (adrenal
cortex).
• Adrenal medulla
– receives neural input from axons of
sympathetic division of the autonomic
nervous system, and secretes epinephrine
and norepinephrine in response
74
Adrenal Glands
• Adrenal cortex
– Hormones from adrenal cortex are
collectively referred to as corticosteroids.

Cortisol maintains glucose homeostasis,
and modulates some aspects of the
immune response.

Aldosterone stimulates the kidneys to
reabsorb Na+
and secrete K+
into the
urine.
75
Adrenal Glands
76
Cortex
Medulla
Capsule
Adrenal vein
ADRENAL/SUPRARENAL GLAND
The adrenal embryologically is a composite of the:
medulla derived from ectoder mal neural-crest cells; &
cortex formed from mesoder m next to the mesonephros
77
ADRENAL CORTEX
Cortex
Zona glomerulosa
Zona fasciculata
Zona reticularis
]
]
small balls of cells
straight bundles of paler cells
cords of cells in a network
sparse
Stroma of
reticular
fibers &
vessels
Capsule
78
ADRENAL CORTICAL HORMONES
Cortex
Zona glomerulosa
Zona fasciculata
Zona reticularis
]
]
makes mineralocorticoids, e.g.,
aldosterone
makes glucocorticoids, e.g., cortisol
makes sex steroids, e.g., androstenedione
79
Zona glomerulosa regulated by
Renin-angiotensin system
Zona fasciculata driven by ACTH
Zona reticularis driven by LH & ACTH
]
]
to make & release mineralocorticoids
to make glucocorticoids
to make sex steroids* & glucocorticoids
Zona-fasciculata steroid-synthesizing cell
Cholesterol droplets
(often dissolved out)
Smooth ER, often tubular
(bag-of-worms visual effect)
Mitochondria with tubular
cristae
dehydroepiandrosterone*
80
Zona glomerulosa
regulated by
Renin-angiotensin
system
mineralocorticoids
glucocorticoids
sex steroids* &
glucocorticoids
]
]
Zona reticularis
driven by LH & ACTH
Zona fasciculata
driven by ACTH
81
Zona-fasciculata steroid-synthesizing cell
Cholesterol droplets
(often dissolved out)
Smooth ER, often tubular
(bag-of-worms visual effect)
Mitochondria with
tubular cristae
Inner mitochondrial
membrane has a P450
enzyme for steroid
biosynthesis
82
Zona glomerulosa ]
JG cells
Renin
Converting
Enzyme
DISTAL
TUBULE
Angiotensinogen
Angiotensin I
Angiotensin II
Aldosterone
Vasoconstriction
Sodium + water
reabsorption (so blood pressure up)
JUXTAGLOMERULAR APPARATUS 6
Outside
kidney
Renin is a protease
83
Aldosterone
Zona glomerulosa
JG cells
Renin
Converting
Enzyme/ ACE
Angiotensinogen
Angiotensin I
Angiotensin II
Vasoconstriction
RENIN-ANGIOTENSIN SYSTEM
DISTAL
TUBULE
Outside
kidney
ACE is in many tissues, and the angiotensin II
receptor is widespread, so that the RA system
is very endocrine in affecting most of the
body, not just vessels, adrenal & kidney
84
ADRENAL MEDULLA
Chromaffin cells
Sympathetic axons
Central vein
Occasional neuron
terminating
mainly on
chromaffin
cells
Chromaffin cells so named, because of chromaffin reaction
- a brown darkening of medulla seen when catecholamines
react with dichromate & other oxidising agents
85
ADRENAL MEDULLA
Chromaffin cells
make epinephrine
& norepinephrine
Sympathetic axons
Central vein
Occasional neuron
terminating
mainly on
chromaffin cells
Epinephrine & norepinephrine are catecholamines stored,
in association with the protein chromogranin, in dense-
cored granules/ vesicles. E & NE augment sympathetic
autonomic nervous-system actions
86
CATECHOLAMINE SYNTHESIS
Chromaffin cells make epinephrine & norepinephrine
TYROSINE
tyrosine hydroxylase
DOPA/Dihydroxyphenylalanine
DOPAMINE
aromatic L-amino acid decarboxylase/AADC
dopamine β-hydroxylase/DBH
NOREPINEPHRINE
EPINEPHRINE/Adrenalin
phenylethanolamine-N-methyltransferase
[rate-limiting?]
87Figure 6.12b
88Figure 21.15
89
Adrenal gland hormones
Regulation Glands Hormones Target
organs
Action Pathology
Reflex Adrenal medulla Epinephrine ANS target
organs
Fight/flight Stress
Blood Pressure Adrenal cortex - Mineralocorticoid =
aldosterone
DCT from renal
tubule
- promote sodium
reabsorption
Not enough"
Addison disease
CRH  ACTH Glucocorticoid =
cortisone
Many cells Mobilize fuels –
stress adaptation
Excess hormone:
Cushing
syndrome
GnRH  GN Estrogen
Testosterone
Sexual organs - Sex organ
maintenance
- Gamete
development
Infertility
90
91
Pancreas
• Located adjacent to the stomach and is
connected to the duodenum by the
pancreatic duct.
– Secretes bicarbonate ions and a variety of
digestive enzymes into small intestine.

β cells of islets of Langerhans secrete
insulin, and α cells secrete glucagon.

antagonistic

Insulin lowers while glucogen
raises blood glucose.
92
PANCREAS
Duodenum
Exocrine acini
digestive enzymes
Lobule
}
Endocrine islet
metabolic hormones
Ducts
alkaline ions
Enteroendocrine cells
hormones
93
Islet of Langerhans
ISLET: Cell types & products
Beta cell - insulin (majority)
Alpha cell - Glucagon
Delta cell - Somatostatin
PP cell - Pancreatic polypeptide
Beta & Alpha cells are directly sensitive to glucose level
94
Antagonistic Actions of Insulin and Glucagon
95
Glucose regulation
• Glucose level controlled by
insulin and glucagon
• Insulin promotes a
decrease in blood glucose
• Glucagon promotes an
increase in blood glucose
96
Glucose regulation
97Figure 3.21
Fate of glucose
98
Diabetes mellitus
• Type I: autoimmune disease  beta cells of
the islets of Langerhans are destroyed by
antibodies
• Type II: The cells become insulin-resistant
 glucose does not enter the cells as
readily
99
Diabetic foot
100
Other Endocrine Glands
• Ovaries and testes
– produce androgen

secondary sexual characteristics
• Pineal gland
– secretes melatonin

regulates biological clocks
101
Other Endocrine Glands
• Molting and metamorphosis in insects
– Hormone secretions influence both
molting and metamorphosis in insects.

Brain hormone stimulates production of
ecdysone (molting hormone).

high levels cause molting to occur

juvenile hormone

high levels prevent transformation to
an adult
102
Other Endocrine Glands
• Endocrine disrupting chemicals
– chemicals that interfere with hormone
function

Any chemical that can bind to receptor
proteins and mimic the effects of the
hormone is called a hormone agonist.

Any chemical that binds to receptor
proteins and has no effect, but blocks
the hormone from binding is a hormone
antagonist.
103
Cerebral
Cortex
Cerebellum
Pineal gland
Brain Stem
Eye & optic
nerve
Central sympathetic
pathways
Suprachiasmatic
nucleus
Thoracic cord
Sympathetic
preganglionic
S Cervical ganglion
Sympathetic
postganglionics
PINEAL ACTIVATION PATHWAY
1
3
4
2
5
7
Darkness increases HIOMT
enzyme to make melatonin HydroxyIndole-O-MethylTransferase
1 7
6
104
Cerebral Cortex
Cerebellum
Pineal gland
Brain Stem
Eye & optic
nerve
Central sympathetic
pathways
Suprachiasmatic
nucleus
Thoracic cord
Sympathetic
preganglionic
S Cervical ganglion
Sympathetic
postganglionics
PINEAL ACTIVATION PATHWAY
1
3
4
2
5
6
1 7
7 melatonin
light off
Melanopsin in retinal ganglion cells
is the photosensitive mediator
105
Cerebral Cortex
Cerebellum
PINEAL GLAND
Brain Stem
Eye & optic
nerve
Central sympathetic
pathways
Suprachiasmatic
nucleus
Thoracic cord
Sympathetic
preganglionic
S Cervical ganglion
Sympathetic
postganglionics
PINEAL ACTIVATION PATHWAY
1
3
4
2
5
7
Darkness increases HIOMT
enzyme to make melatonin HydroxyIndole-O-MethylTransferase
6
melatonin
light off
106
cvlAl
re
uo
- - - - - - -
ENDOCRINE ORGANS II
Plus neuroendocrine cells
developed within mature
gut, airway, etc epithelia
[Kidney]
[Heart] ANF
EPO
Renin
VIP
Gastrin
Secretin, etc
Gonads
[Placenta]
hCG
Estrogen
Progesterone
Sex steroids
[Adipose
tissue]
Leptin
107
ATRIAL HEART & ANF
Atrial myocytes have a well developed Golgi complex and
secretory granules
Reticular fiber
Atrial Natriuretic Factor (ANF) in the granules STIMULATES:
diuresis; sodium excretion (natriuresis); vasorelaxation;
& INHIBITS the Renin-Angiotensin system & aldosterone
secretion
108
Enteroendocrine cell types I
Enteroendocrine cell
small, pale, few; granules
are located basally for
release into the lamina
propria
Entero is misleading because: some cell
types are confined to the stomach; and
peptides & amines are signaling agents in
other epithelia and other systems e.g. brain
G cell - gastrin
S cell - secretin
I cell - cholecystokinin
ECL cell - histamine
D cell (antral) - somatostatin
EC cell - serotonin
A cell - ghrelin
109
Enteroendocrine cell types II
Motilin cell: why not ‘M’ cell? There already is one, involved in immunity
G cell - gastrin
S cell - secretin
I cell - cholecystokinin
ECL cell - histamine
L cell - glucagon-like peptide (GLP-1 & 2)
peptide Y (PYY)
oxyntomodulin
K cell - gastric inhibitory
polypeptide/GIP
N cell - neurotensin
M? cell - motilin
D cell (antral) - somatostatin
Coordinated with extrinsic &
intrinsic neural controls and
interacting amongst
themselves
EC cell - serotonin
A cell - ghrelin
110
EXOCRINE PANCREAS Controls
Duodenum
Exocrine aciniEnteroendocrine cells
Secretin & CCK
digestive enzymes
HCO3
-
ions
RESPONSE
Acid Fats Peptides
STIMULI
CONTROLLER
+ Vagal cholinergic control
111
SOURCES OF ‘GUT’ HORMONES
RECTUM
LIVER
PANCREAS
GALL
BLADDER
STOMACH
SMALL
GUT
LARGE
GUT
Bile
gastrin ghrelin
Duodenum
cholecystokinin motilin
somatostatin
neurotensin
GIP-1
GLP-1&2
Peptide Y
insulin glucagon
PPY somatostatin
secretin
Oxyntomodulin
112
SOURCES OF ‘GUT’ HORMONES
PANCREAS
STOMACH
SMALL GUT
LARGE GUT
gastrin ghrelin
Duodenum cholecystokinin motilin
somatostatin
neurotensin
GIP-1
GLP-1&2 Peptide Y
insulin glucagon PPY somatostatin
secretin
Oxyntomodulin
113
Enteroendocrine cell types III
Immunostaining for the peptide or chromogranin and
fluorescence methods for the amine derivatives now provide
clear identification of the cells, but against a background of the
old silver-based cell nomenclature
A messy story*, because of the various staining reactions of
enteroendocrine cells (particularly with silver methods) based on the
peptide hormones, the associated chromogranin storage protein in
the granules, and any catecholamine, serotonin or histamine
content.
ECL cell - EnteroChromaffin-Like cell
114
Adipocyte hormones & other metabolic players
RECTUM
LARGE
GUT
LIVER
SMALL
GUT
STOMACH
PANCREAS
GALL
BLADDER
E
S
O
P
H
A
G
U
S
MOUTH
APPENDI X
SALIVARY
GLAND
AIRWAY
HYPOTHALAMUS
Appetites
Homeostasis
Emotion
CEREBRAL CORTEX
Cerebellum
Pons
Mid-
brain
Medulla
PITUITARY
TALUS
CALCANEUS Metatarsa
l
FEMUR
Fat cell
Adipocytes
MUSCLE
115
Adipocyte hormones -
LIVER
HYPOTHALAMUS
TALUS
CALCANEUS Metatarsa
l
FEMUR
Fat cell
Adipocytes
MUSCLE
LEPTIN
ADIPONECTIN
for energy balance and
glucose homeostasis
116
Visceral/abdominal fat & type II diabetes, etc
LIVER
HYPOTHALAMUS
TALUS
CALCANEUS Metatarsa
l
FEMUR
Fat cell
Adipocytes
MUSCLE
LEPTIN
ADIPONECTIN
MACROPHAGES(MΦs)
Macrophages accumulate in the stroma of
the fatty tissue, become activated to
release abnormal cytokines , e.g., TNF-
α ,that disrupt many metabolic pathways
so that the visceral adipose tissue is
permanently inflamed and dangerous, e.g.
Adipocyte production of adiponectin falls
Insulin signalling goes bad, etc.
117
TESTIS & LEYDIG CELLS
Peritubular
myoid cells
LEYDIG
INTERSTITIAL
CELLS
Acidophil
Much smooth ER
Lipid droplets
Crystals of Reinke
SERTOLI CELLS
Sperm
layered
SPERMATOGENIC CELLS
{stratified
germinal
epithelium
BASAL LAMINA
SEMINIFEROUS
TUBULE
SEMINIFEROUS
TUBULE
118
HORMONES
PITUITARY
GONADOTROPHS
HYPOTHALAMIC
NEURONS
INTERSTITIAL
CELLS
SEMINIFEROUS
TUBULE
PENIS
SEMINAL
VESICLE
PROSTATE
RETE
TESTIS
TUBULUS
RECTUS EFFERENT
DUCT
EPIDIDYMIS
DUCTUS
DEFERNS
BULBOURETHRAL
GLAND
urethra
Androgens
Courtship
& Coital
behaviors
GnRHFSH
LH
1
2 3
4
5 Secondary
sexual
characters
6
7
Somatic growth &
metabolism

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Endocrine system

  • 2. 2 Outline • Types of Regulatory Molecules • Endocrine Glands and Hormones • Paracrine Regulation • Hormones That Enter Cells • Hormones That Do Not Enter Cells • Posterior and Anterior Pituitary Gland • Thyroid and Parathyroid Glands • Adrenal Glands • Other Endocrine Glands
  • 3. 3 SIGNALING AGENTS & FACTORS Neurotransmitters Peptides Oxygen-based molecules, e.g., NO Prostanoids Hormones Cytokines ( some are Chemokines) Extracellular-matrix molecules Nutrients & metabolites Mechanical stimuli, e.g., fluid shear Cell-surface glycoproteins Hormones from endocrine cells & organs are part of a much larger picture of the outside controls on cells Heat, osmolarity, exogenous chemicals, etc ENDOCRINE
  • 4. 4 Types of Regulatory Molecules • Hormone – A regulatory chemical secreted into the blood by an endocrine gland, or an organ exhibiting endocrine function. • Target Cells respond to hormone – Neurohormone – A chemical messenger secreted by neuron into the blood rather than the synaptic cleft. • Paracrine - regulatory molecules work without being transmitted by the blood – not endocrine • Pheromone - communication messengers
  • 5. 5 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Axon Neurotransmitter Endocrine gland Paracrine regulator Receptor proteins Hormone carried by blood Target cell
  • 6. 6 Endocrine Glands and Hormones • Hormones secreted by the endocrine glands belong to four chemical categories: – Polypeptides - short chains of amino acids less than 100 amino acids (insulin & ADH) – Glycoproteins- longer than100 A.A. with carbs (FSH and LH) – Amines - Amines – A.A. derived from tyrosine and tryptophan – epinephrine and norepinephrine and melatonin – Steroids - lipids derived from cholesterol  sex steroids - testosterone, estadiol, progesterone, and cortisol – secreted by testes, ovaries, placenta and adrenal cortex  Corticosteroids - adrenal cortex cortisol and aldosterone (regulates glucose and salt balance) – All hormones can be categorized as lipophilic (fat soluble) or hydrophilic (water soluble).
  • 7. 7 Endocrine Glands and Hormones • Neural and endocrine interactions – Endocrine system also interacts and cooperates with the nervous system to regulate the activities of the other organ systems of the body. – Secretory activity of many endocrine glands controlled by nervous system like  Adrenal medulla, posterior pituitary, and pineal gland  major site for neural regulation is the brain’s regulation of the anterior pituitary by the hypothalmus However many are not under neural control
  • 9. 9 cvlAl re u o - - - - - - - diaphragm Parathyroids Adrenal cortex Thyroid Pituitary anterior Pancreas Gonads ENDOCRINE ORGANS I
  • 10. 10 [ non-epithelial origin ] cvlAl re uo - - - - - - - diaphragm Parathyroids Adrenal cortex Thyroid Pituitary anterior Pancreas Gonads ENDOCRINE ORGANS II [Pineal] [Heart] [Adrenal medulla] [Kidney] [Placenta] Plus neuroendocrine cells developed within mature gut, airway, etc epithelia [Pituitary, posterior & Brain] [Adipose tissue]
  • 11. 11 TYPICAL ENDOCRINE GLAND - Context hormone release vessels Clumps of endocrine cells blood control Capillary diffusion TARGET ORGAN Target cells, with receptors for binding 12 transport3 4 5 Target cells’ response 6 Feedback
  • 12. 12 GLAND(S) WHERE CELL TYPES HORMONES SPECIAL Thyroid Neck Follicular cells C cells Thyronine Calcitonin Follicles for storage Parathyroid Neck Chief cells Parathormone /PTH Small Adrenal medulla Over kidney Chromaffin cells Epinephrine Norepinephrine Nerve fibers Adrenal cortex Over kidney Zona glomerulosa Zona fasciculata Zona reticularis Mineralocorticoids Glucocorticoids Sex steroids Pineal Brain’s center Pinealocytes Melatonin Connected for light drive Zones ENDOCRINE ORGANS I
  • 13. 13 GLAND(S) WHERE CELL TYPES HORMONES SPECIAL Pituitary posterior Axons of PV & SO hypothal. neurons Oxytocin Vasopressin /ADH Extension of brain Pancreas Left upper quad Beta, Alpha, Delta, PP cells Insulin Glucagon Somatostatin Pancr Peptide Gonads Pelvic/ Scrotal Granulosa, Theca Lutein, & Leydig Sex steroids Inhibin Placenta Uterus Syncytiotrophoblast Female: for amplified hormonal responses Female: cyclic Pituitary anterior Below brain MTs STs GTs THs CTs Blood drains hypothal.- pituitary for control Prolactin GH LH FSH TSH ACTH Below brain Islets +Pituicytes s ENDOCRINE ORGANS II
  • 14. 14 Paracrine Regulation • Signaling between cells - Local effect and short-lived occurs in many organs • Regulatory molecules – cytokines - regulate different cells of the immune system – growth factors - promote growth and cell division in specific organs – stimulate cell division at target cells
  • 15. 15 Paracrine Regulation • Prostaglandins – most diverse group of paracrine regulators • participate in regulation of: – immune system – inflammation, pain and fever – reproductive system – reproductive function ovulation, labor, – digestive system – inhibit gastric secretions, incrfease motility and fluid absorption – respiratory system - blood vessels constriction and dilation in lungs – circulatory system - blood platelets in blood clotting – urinary system - renal blood flow vasodilation increasing urine excretion • Prostaglandin synthesis inhibited by aspirin. – nonsteroidal anti-inflammatory drug  Ibuprofen  Work to inhibit inflammation and pain by inhibiting enzyme necessary to produce prostaglandins – (cyclooxygenase -2)
  • 16. 16 Hormones That Enter Cells • Lipophilic hormones pass through the target cell’s plasma membrane and bind to intracellular receptor proteins. – hormone receptor complex then binds to specific regions of DNA  activate genes and regulate target cells
  • 18. 18 Hormones That Do Not Enter Cells • Hormones that are too large or too polar to cross plasma membranes include all of the peptide and glycoprotein hormones, as well as catecholamine hormones epinephrine and norepinephrine. – bind to receptor proteins located on the outer surface of the plasma membrane  cyclic AMP second-messenger system  IP3/CA++ second-messenger system
  • 19. 19 Action of Epinephrine on a Liver Cell 1. Epinephrine is lipophobic and needs to bind to specific receptor proteins on cell surface. 2. Acting through intermediary G proteins the hormone bound receptor activates the enzyme adenenylyl cyclase which converts ATP to cAMP 3. Cyclic AMP performs as a 2ndary messenger and activates protein kinase-A an enzyme that was previously inactive 4. Protein kinase–A phosphorylates and activates the enzyme phosphorylase which catalyses the hydrolysis of glycogen into glucose.
  • 20. 20 IP3/CA++ Second-Messenger System 1. The hormone epinephrine binds to specific receptor proteins on the cell surface. 2. Acting through G- proteins, the hormone-bound receptor activates the enzyme phospholipase C, which converts membrane phospholipids into inositol triphosphate (IP3) 3. IP3 diffuses thru the cytoplasm and binds to receptors on the endoplasmic reticulum 4. The binding of IP3 to the receptor stimulates the endoplasmic reticulum to release Ca++ into the cytoplasm 5. Some of the released Ca++ binds to the receptor protein called calmodulin 6. The Ca++/Calmodulin complex activates other intracellular proteins – producing the horomone effects
  • 21. 21 Primary endocrine organs • Hypothalamus and pituitary gland secrete hormones and regulate other endocrine organs. They are the main regulatory organs of the endocrine system.
  • 22. 22 Hypothalamus • Located below the thalamus and above the pituitary gland (=epiphysis) • Regulates the pituitary gland secretions through two different mechanisms
  • 23. 23 Hypothalamus - neurohypophysis • 1- Neurons, receiving information from receptors, fire APs which travel down to the post pituitary gland and stimulate the release of stored neurohormones – Oxytocin (OT) and anti- diuretic hormone (ADH)
  • 24. 24 Hormones of the posterior pituitary Regulation Hormone Target organ Action Pathology Reflex Oxytocin - Uterus (smooth muscle) - breast tubules (smooth muscles) -labor and delivery - milk-let down -- -- Reflex (osmoreceptor) ADH (vasopressin) - DCT in kidney tubules - promote H2O reabsorption - not enough: diabetes insipidus - too much: ↑ BP?
  • 25. 25 Hypothalamus – adenohypophysis • 2- Upon stimulation, secretory cells located in the hypothalamus secrete “releasing” hormones which travel down a capillary bed toward the anterior pituitary gland (adenopituitary). Each type of releasing hormones will stimulate the secretion and release of a pituitary hormone. • Hormones which control the secretion of other hormones are tropic hormones (found in hypothalamus and pituitary gland
  • 26. 26Figure 6.5 Hormones of the hypothalamus and anterior pituitary gland
  • 27. 27Figure 6.8 Anterior pituitary Regulation Hormone Target organ Action Pathology GHRH and GHIH Growth hormone (GH) Many cells (bones..) Stimulate cell growth and cell division - not enough: children  pituitary dwarfism too much: gigantism (children) – acromegaly (adult) PRH - PIH Prolactin (PL) Breast secretory cells - milk secretion -- TRH Thyroid stimulating hormone (TSH) Thyroid gland - promote thyroid gland secretion (T3 and T4) - not enough: hypothyroidism (cretinism in children) - too much: hyperthyroidism CRH Adrenocorticotropic hormone (ACTH) Adrenal cortex (3 layers) - stimulates secretion of adrenal cortex - not enough: Addison's disease - too much: Cushing syndrome GnRH Gonadotropin - Follicle stimulating hormone (FSH) - Luteinizing hormone (LH) Stimulate gamete maturation Stimulate gonadal gland secretion and gamete formation - infertility
  • 28. 28 Figure 23-17 Same Individual with Acromegaly (evolution over 20 years)
  • 30. 30 HYPOPHYSIS/ Pituitary gland Pituitary stalk Posterior lobe Hypoth alamus Anterior lobe Dura IIIrd Ve Intermediatelobe
  • 31. 31 Pars nervosa Infundibular process Pars intermedia PITUITARY SUB-DIVISIONS Hypothalamic SO & PV nuclei Hypothalamic median eminence ADENOHYPOPHYSIS Pars distalis Pars tuberalis NEUROHYPOPHYSIS Infundibular stem neural part of stalk 1 3 2 1 2 3
  • 32. 32 Unlike some other endocrine cells, those of the anterior pituitary separate their supplying a hormone from the detection of the need for the hormone. The sensitivity to need is performed by hypothalamic neurons, which can coordinate requirements for several hormones with drives, and events outside the person. Anterior-pituitary cells & hormones The system also allows for control by inhibitory factors, as well as + driving hormone-releasing factors
  • 33. 33 HYPOTHALAMO-HYPOPHYSEAL Portal flow Superior arteries Portal drainage Hypothalamus Anterior lobe capillaries Dura Hypothalamic capillary bed Neurosecretory neurons Veins 1 2 3 4 5 A portal flow takes venous blood drained from one organ and uses it as a supply to another organ, e.g., gut to liver
  • 34. 34 HYPOTHALAMO-HYPOPHYSEAL Portal flow Superior arteries Portal drainage Hypothalamus Anterior lobe capillaries Hypothalamic capillary bed Neurosecretory neurons Veins 1 2 3 4 5 Portal flow carries factors from hypothalamic neurons to pituitary anterior-lobe cells E.g.,TH-RF from neuron causes Thyrotroph to release TSH
  • 35. 35 Superior arteries Portal drainage Hypothalamus Anterior lobe capillaries Hypothalamic capillary bed Neurosecretory neurons Veins 1 2 3 4 5 Mammotrophs MTs Somatotrophs STs Gonadotrophs GTs Thyrotrophs THs Corticotrophs CTs Blood drains hypothalamus-pituitary for control by RFs, etc Prolactin PRL Growth hormone GH Luteinizing hormone LH Follicle-stimulating hormone FSH Thyroid-stimulating hormone TSH Adrenocorticotrophic hormone ACTH Anterior-pituitary cells & hormones
  • 36. 36 Mammotrophs MTs Somatotrophs STs Gonadotrophs GTs Thyrotrophs THs Corticotrophs CTs Blood drains hypothalamus- pituitary for control by RFs, etc Prolactin PRL Growth hormone GH Luteinizing hormone LH/ICSH Follicle-stimulating hormone FSH Thyroid-stimulating hormone TSH Adrenocorticotrophic hormone ACTH cleaved from pro-opio-melanonocortin/ POMC Anterior-pituitary cells & hormones Acidophil Basophil
  • 37. 37 Anterior-pituitary cells 2 Mammotrophs MTs Somatotrophs STs Gonadotrophs GTs Thyrotrophs THs Corticotrophs CTs Prolactin PRL Growth hormone GH Luteinizing hormone LH FSH TSH ACTH Acidophil Basophil Chromophobe Chromophobes stain weakly, in comparison to CHROMOPHILS - Acidophils & Basophils Folliculo-Stellate cells lie amongst the glandular cells; doing what?
  • 38. 38 Anterior-pituitary cells 3 Corticotrophs CTs ACTH but by selective enzymatic cleavage of a larger 32kDa precursor - pro-opiomelanocortin, also made in the hypothalamus and elsewhere, and there serving to provide other hormones & neurotransmitters Pro-opiomelanocortin ACTH Pro-ACTH β-LPH β-Endorphin β- MSH SP simplified POMC ~ Pro-opiomelanocortin
  • 39. 39 Anterior-pituitary cells 4 Selective enzymatic cleavage of the precursor - pro- opiomelanocortin, provides other hormones & transmitters ACT H β-Endorphin Pro-opiomelanocortinSP NT 1-76 β-LPHACTH β-LPHACTH γ-LPH NT 1-49 JP γ -MSH α-MSH β-MSH elaborate MSH ~ Melanocyte-stimulating hormone NT ~ amino-terminal peptides LPH ~ Lipotropic hormone Pro-hormone convertase 1 Pro-hormone convertase 1 Pro−γ -MSH Pro−γ -MSH After Reudelhuber TL. J Clin Invest 2003;111:1115-1116
  • 40. 40 NEUROHYPOPHYSIS Pars nervosa Hypothalamic SO & PV nuclei Supraoptic & Paraventricular nuclei Hypothalamus 1 2 3 Inferior arteries Veins Release of hormone is separated from production * * * * Neural stalk Optic chiasm
  • 41. 41 NEUROHYPOPHYSIS Pars nervosa Hypothalamic SO & PV nuclei Supraoptic & Paraventricular nuclei Hypothalamus 1 2 3 Inferior arteries Veins * * Neural stalk Optic chiasm Note - the supraoptic nucleus is above the optic nerve & chiasm, but closer to the chiasm is the small suprachiasmatic nucleus (relaying the darkness stimulus indirectly to the pineal gland).
  • 42. 42 NEUROHYPOPHYSIS Pars nervosa axons, terminals, pituicytes & capillaries Hypothalamic SO & PV nucleiHypothalamus Infundibular stem neural part of stalk - axons & glia 1 2 3 Neurosecretory neurons producing oxytocin & vasopressin/ADH Inferior arteries Veins Release of hormone is separated from production * * * *
  • 43. 43 NEUROHYPOPHYSIS Hypothalamic SO & PV nucleiHypothalamus Neurosecretory neurons producing oxytocin & vasopressin/ADH Inferior arteries Veins Hormone travels down the axon bound to the carrier protein - neurophysin, from which it is cleaved for release * *
  • 44. 44 SUCKLING REFLEX Hypothalamic SO & PV neuron activation Hypothalamus * BREAST Myoepithelial-cell contraction Sensory response Oxytocin release Stimulus1 2 3 4 56 7 Milk ejectionVascular transfer
  • 45. 45 PITUITARY Mid-sagittal section of 1-m embryo STOMODEUM PHARYNGEAL ARCHES PITUITARY RATHKE’S POUCH starting in oral ectoderm BRAIN I II
  • 46. 46 PITUITARY DEVELOPMENT II Neural-tube diencephalic ectoderm Oral-pharyngeal lining ectoderm IIIrd Ve Rathke’s pouch Pars tuberalis Pars distalis Pars intermedia Pars nervosa Infundibular stem Hypothalamus ADENOHYPOPHYSIS NEUROHYPOPHYSIS
  • 47. 47 PITUITARY DEVELOPMENT II Pars tuberalis Pars distalis Pars intermedia Pars nervosa Infundibular stem Hypothalamus Pars nervosa Infundibular process Pars intermedia Hypothalamic SO & PV nuclei Hypothalamic median eminence ADENOHYPOPHYSIS Pars distalis Pars tuberalis NEUROHYPOPHYSIS Infundibular stem neural part of stalk1 3 2 1 2 3 Cysts Cysts in Pars intermedia - remnants of Rathke’s pouch lumen? Rathke’s pouch lumen
  • 48. 48 Pars nervosa/ Infundibular process Pars intermedia Hypothalamic SO & PV nuclei Hypothalamic median eminence ADENOHYPOPHYSIS Pars distalis Pars tuberalis NEUROHYPOPHYSIS Infundibular stem/ neural part of stalk1 3 2 1 2 3 Cysts Cysts in Pars intermedia - remnants of Rathke’s pouch lumen?
  • 49. 49 Posterior Pituitary Gland • Pituitary gland hangs by a stalk from the hypothalamus of the brain. – anterior pituitary - appears glandular – posterior pituitary - appears fibrous • Neurons produce antidiuretic hormone (ADH) and oxytocin. – stored in, and released from, the posterior pituitary gland in response to neural stimulation from the hypothalamus
  • 51. 51 Anterior Pituitary Gland • Develops from a pouch of epithelial tissue that pinches off the roof of the embryo’s mouth. – produces the hormones it secretes:  growth hormone (GH) stimulates muscles and bones to grow  adrenocorticotropic hormone (ACTH) regulates glucose homeostasis  thyroid-stimulating hormone (TSH) stimulates the production of thyroxin by thyroid gland  luteinizing hormone (LH) ovulation and testosterone production in testes  follicle-stimulating hormone (FSH) develops ovarian follicle and sperm in males  prolactin (PRL) stimulates mammary glands to produce milk  melanocyte-stimulating hormone (MSH) synthesis and dispersion of melanin pigment
  • 53. 53 Anterior Pituitary Gland • Hypothalamic control of anterior pituitary gland secretion – Neurons in the hypothalamus secrete releasing hormones and inhibiting hormones into blood capillaries at the base of the hypothalamus.  Each hormone delivered by hypothalamohypophysial portal system regulates secretion or inhibition of a specific anterior pituitary hormone.
  • 54. 54 Neurons in the hypothalamus secretes hormones that are carried by short blood vessels directly to the ant. Pituitary gland, where they either stimulate or inhibit the secretions of the ant pituitary hormones Cell body Axons to primary capillaries Primary capillaries Pituitary stalk Posterior pituitary Anterior pituitary Secondary capillaries Portal venules
  • 55. 55 Anterior Pituitary Gland • Negative feedback inhibition acts to maintain relatively constant levels of the target cell hormone. – Positive feedback cannot maintain constancy of the internal environment.
  • 56. 56 Negative Feedback Inhibition Hormones secreted by some endocrine glands feed back to inhibit the secretion of hypothalamic releasing hormones and anterior pituitary hormones
  • 57. 57 Thyroid and Parathyroid Glands • Thyroid gland – Shaped like a shield and lies just below the Adam’s apple in the front of the neck.  Thyroxine helps set basal metabolic rate by stimulating the rate of cell respiration.  In children, thyroid hormones also promote growth and stimulate maturation of the central nervous system.  unique function in amphibians - metamorphosis from larvae into adults
  • 59. 59 Thyroid and Parathyroid Glands • Parathyroid gland and calcium homeostasis – four small glands attached to the thyroid  produces parathyroid hormone (PTH)  one of only two hormones in humans that are absolutely essential for survival  stimulates osteoclasts in bone to dissolve calcium phosphate crystals and release Ca++ into the blood
  • 60. 60 Regulation of Blood Calcium Levels
  • 61. 61 Calcium Metabolism: Figure 23-20: Calcium balance in the body
  • 63. 63 THYROID GLAND Follicular cells simple cuboidal epithelium Colloid / Thyroglobulin glycoprotein = PAS+ Follicles for storage C cells/ Parafollicular cells Capillaries In the section, the follicles do not hold their spherical shape this well, and the colloid displays knife chatters and variable staining
  • 64. 64 THYROID GLAND: Physiological variablity Follicular cells high cuboidal when very active; squamous when inactive Colloid / Thyroglobulin less in active state, excessive in goitre Follicles - size varies inversely with activity C cells/ Parafollicular cells for calcitonin Capillaries
  • 65. 65 GOLGI Amino acids Sugars Iodine Thyroglobulin Endocytosis Cleavage Release of hormones T3 & T4 Synthesis & iodination of thyroglobulin THYROID FOLLICULAR CELL TSH
  • 66. 66 Goiter • Both hypo and hyperthyroidism can have goiter as a symptom • Goiter is a swelling of the neck due to hypertrophy of the thyroid gland • How can one explain that?
  • 67. 67 Goiter in hypothyroidism • Most often due to a lack of dietary iodine • The thyroid hormone is unable to synthesize a functional thyroid hormone (T3 and T4) • The person express symptoms of hypothyroidism • The nonfunctional T3/T4 cannot promote a negative feedback on TRH and TSH   the hypotalamus and pituitary gland increase their secretions  the thyroid gland is stimulated to secrete more T3 and T4 … • In children, the lack of functional T3/T4 result in cretinism, a form a mental retardation
  • 68. 68 Goiter in hyperthyroidism • The cells secreting TRH or TSH on the hypothalamus and pituitary gland (respectively) have become abnormal and no longer are sensitive to the negative feedback  they continue to secrete TRH or TSH  continuous stimulation of the thyroid gland with excess thyroid hormones being formed   symptoms of hyperthyroidism
  • 69. 69 PARATHYROID GLAND Oxyphil cells Chief cells Characteristic is the lack of obvious general structural features Small, pale, resemble lymphocytes, but have more cytoplasm Larger, eosinophilic, darker nuclei, packed with mitochondria
  • 70. 70 PARATHYROID GLAND OXYPHIL CELLS CHIEF CELLS have membrane calcium sensors to respond to low Ca2+ by releasing parathyroid hormone /PTH. PTH stimulates osteoclasts to release Ca2+ from bone & has conserving renal effects derivatives of Chief cells
  • 71. 71 Osteoclast Ruffled border agitating released enzymes & acid Eaten-out hole is a Howship’s lacuna BONE REMODELING Osteoclasts as a team eating out a resorption tunnel Sealing ring of tight attachment to bone BONE MATRIX BONE
  • 72. 72 ONCOCYTIC CONVERSION As cuboidal epithelia and glands age, a few of their epithelial cells lose most of their normal organelles and fill up with mitochondria. Mitochondria-rich cells are eosinophilic. This event results in two classes of cell: those that are functioning normally and need many mitochondria - gastric parietal cells, renal proximal-tubular cells, striated-duct cells, etc; & non-functional mitochondria-stuffed cells in older epithelia. These have acquired two names: the usual - oncocyte, and, as an exception, the archaic oxyphil cell in the parathyroids. & Hurthle cells in thyroid :
  • 73. 73 Adrenal Glands • Adrenal glands are located above each kidney. – Each gland composed of inner portion (adrenal medulla) and outer layer (adrenal cortex). • Adrenal medulla – receives neural input from axons of sympathetic division of the autonomic nervous system, and secretes epinephrine and norepinephrine in response
  • 74. 74 Adrenal Glands • Adrenal cortex – Hormones from adrenal cortex are collectively referred to as corticosteroids.  Cortisol maintains glucose homeostasis, and modulates some aspects of the immune response.  Aldosterone stimulates the kidneys to reabsorb Na+ and secrete K+ into the urine.
  • 76. 76 Cortex Medulla Capsule Adrenal vein ADRENAL/SUPRARENAL GLAND The adrenal embryologically is a composite of the: medulla derived from ectoder mal neural-crest cells; & cortex formed from mesoder m next to the mesonephros
  • 77. 77 ADRENAL CORTEX Cortex Zona glomerulosa Zona fasciculata Zona reticularis ] ] small balls of cells straight bundles of paler cells cords of cells in a network sparse Stroma of reticular fibers & vessels Capsule
  • 78. 78 ADRENAL CORTICAL HORMONES Cortex Zona glomerulosa Zona fasciculata Zona reticularis ] ] makes mineralocorticoids, e.g., aldosterone makes glucocorticoids, e.g., cortisol makes sex steroids, e.g., androstenedione
  • 79. 79 Zona glomerulosa regulated by Renin-angiotensin system Zona fasciculata driven by ACTH Zona reticularis driven by LH & ACTH ] ] to make & release mineralocorticoids to make glucocorticoids to make sex steroids* & glucocorticoids Zona-fasciculata steroid-synthesizing cell Cholesterol droplets (often dissolved out) Smooth ER, often tubular (bag-of-worms visual effect) Mitochondria with tubular cristae dehydroepiandrosterone*
  • 80. 80 Zona glomerulosa regulated by Renin-angiotensin system mineralocorticoids glucocorticoids sex steroids* & glucocorticoids ] ] Zona reticularis driven by LH & ACTH Zona fasciculata driven by ACTH
  • 81. 81 Zona-fasciculata steroid-synthesizing cell Cholesterol droplets (often dissolved out) Smooth ER, often tubular (bag-of-worms visual effect) Mitochondria with tubular cristae Inner mitochondrial membrane has a P450 enzyme for steroid biosynthesis
  • 82. 82 Zona glomerulosa ] JG cells Renin Converting Enzyme DISTAL TUBULE Angiotensinogen Angiotensin I Angiotensin II Aldosterone Vasoconstriction Sodium + water reabsorption (so blood pressure up) JUXTAGLOMERULAR APPARATUS 6 Outside kidney Renin is a protease
  • 83. 83 Aldosterone Zona glomerulosa JG cells Renin Converting Enzyme/ ACE Angiotensinogen Angiotensin I Angiotensin II Vasoconstriction RENIN-ANGIOTENSIN SYSTEM DISTAL TUBULE Outside kidney ACE is in many tissues, and the angiotensin II receptor is widespread, so that the RA system is very endocrine in affecting most of the body, not just vessels, adrenal & kidney
  • 84. 84 ADRENAL MEDULLA Chromaffin cells Sympathetic axons Central vein Occasional neuron terminating mainly on chromaffin cells Chromaffin cells so named, because of chromaffin reaction - a brown darkening of medulla seen when catecholamines react with dichromate & other oxidising agents
  • 85. 85 ADRENAL MEDULLA Chromaffin cells make epinephrine & norepinephrine Sympathetic axons Central vein Occasional neuron terminating mainly on chromaffin cells Epinephrine & norepinephrine are catecholamines stored, in association with the protein chromogranin, in dense- cored granules/ vesicles. E & NE augment sympathetic autonomic nervous-system actions
  • 86. 86 CATECHOLAMINE SYNTHESIS Chromaffin cells make epinephrine & norepinephrine TYROSINE tyrosine hydroxylase DOPA/Dihydroxyphenylalanine DOPAMINE aromatic L-amino acid decarboxylase/AADC dopamine β-hydroxylase/DBH NOREPINEPHRINE EPINEPHRINE/Adrenalin phenylethanolamine-N-methyltransferase [rate-limiting?]
  • 89. 89 Adrenal gland hormones Regulation Glands Hormones Target organs Action Pathology Reflex Adrenal medulla Epinephrine ANS target organs Fight/flight Stress Blood Pressure Adrenal cortex - Mineralocorticoid = aldosterone DCT from renal tubule - promote sodium reabsorption Not enough" Addison disease CRH  ACTH Glucocorticoid = cortisone Many cells Mobilize fuels – stress adaptation Excess hormone: Cushing syndrome GnRH  GN Estrogen Testosterone Sexual organs - Sex organ maintenance - Gamete development Infertility
  • 90. 90
  • 91. 91 Pancreas • Located adjacent to the stomach and is connected to the duodenum by the pancreatic duct. – Secretes bicarbonate ions and a variety of digestive enzymes into small intestine.  β cells of islets of Langerhans secrete insulin, and α cells secrete glucagon.  antagonistic  Insulin lowers while glucogen raises blood glucose.
  • 92. 92 PANCREAS Duodenum Exocrine acini digestive enzymes Lobule } Endocrine islet metabolic hormones Ducts alkaline ions Enteroendocrine cells hormones
  • 93. 93 Islet of Langerhans ISLET: Cell types & products Beta cell - insulin (majority) Alpha cell - Glucagon Delta cell - Somatostatin PP cell - Pancreatic polypeptide Beta & Alpha cells are directly sensitive to glucose level
  • 94. 94 Antagonistic Actions of Insulin and Glucagon
  • 95. 95 Glucose regulation • Glucose level controlled by insulin and glucagon • Insulin promotes a decrease in blood glucose • Glucagon promotes an increase in blood glucose
  • 98. 98 Diabetes mellitus • Type I: autoimmune disease  beta cells of the islets of Langerhans are destroyed by antibodies • Type II: The cells become insulin-resistant  glucose does not enter the cells as readily
  • 100. 100 Other Endocrine Glands • Ovaries and testes – produce androgen  secondary sexual characteristics • Pineal gland – secretes melatonin  regulates biological clocks
  • 101. 101 Other Endocrine Glands • Molting and metamorphosis in insects – Hormone secretions influence both molting and metamorphosis in insects.  Brain hormone stimulates production of ecdysone (molting hormone).  high levels cause molting to occur  juvenile hormone  high levels prevent transformation to an adult
  • 102. 102 Other Endocrine Glands • Endocrine disrupting chemicals – chemicals that interfere with hormone function  Any chemical that can bind to receptor proteins and mimic the effects of the hormone is called a hormone agonist.  Any chemical that binds to receptor proteins and has no effect, but blocks the hormone from binding is a hormone antagonist.
  • 103. 103 Cerebral Cortex Cerebellum Pineal gland Brain Stem Eye & optic nerve Central sympathetic pathways Suprachiasmatic nucleus Thoracic cord Sympathetic preganglionic S Cervical ganglion Sympathetic postganglionics PINEAL ACTIVATION PATHWAY 1 3 4 2 5 7 Darkness increases HIOMT enzyme to make melatonin HydroxyIndole-O-MethylTransferase 1 7 6
  • 104. 104 Cerebral Cortex Cerebellum Pineal gland Brain Stem Eye & optic nerve Central sympathetic pathways Suprachiasmatic nucleus Thoracic cord Sympathetic preganglionic S Cervical ganglion Sympathetic postganglionics PINEAL ACTIVATION PATHWAY 1 3 4 2 5 6 1 7 7 melatonin light off Melanopsin in retinal ganglion cells is the photosensitive mediator
  • 105. 105 Cerebral Cortex Cerebellum PINEAL GLAND Brain Stem Eye & optic nerve Central sympathetic pathways Suprachiasmatic nucleus Thoracic cord Sympathetic preganglionic S Cervical ganglion Sympathetic postganglionics PINEAL ACTIVATION PATHWAY 1 3 4 2 5 7 Darkness increases HIOMT enzyme to make melatonin HydroxyIndole-O-MethylTransferase 6 melatonin light off
  • 106. 106 cvlAl re uo - - - - - - - ENDOCRINE ORGANS II Plus neuroendocrine cells developed within mature gut, airway, etc epithelia [Kidney] [Heart] ANF EPO Renin VIP Gastrin Secretin, etc Gonads [Placenta] hCG Estrogen Progesterone Sex steroids [Adipose tissue] Leptin
  • 107. 107 ATRIAL HEART & ANF Atrial myocytes have a well developed Golgi complex and secretory granules Reticular fiber Atrial Natriuretic Factor (ANF) in the granules STIMULATES: diuresis; sodium excretion (natriuresis); vasorelaxation; & INHIBITS the Renin-Angiotensin system & aldosterone secretion
  • 108. 108 Enteroendocrine cell types I Enteroendocrine cell small, pale, few; granules are located basally for release into the lamina propria Entero is misleading because: some cell types are confined to the stomach; and peptides & amines are signaling agents in other epithelia and other systems e.g. brain G cell - gastrin S cell - secretin I cell - cholecystokinin ECL cell - histamine D cell (antral) - somatostatin EC cell - serotonin A cell - ghrelin
  • 109. 109 Enteroendocrine cell types II Motilin cell: why not ‘M’ cell? There already is one, involved in immunity G cell - gastrin S cell - secretin I cell - cholecystokinin ECL cell - histamine L cell - glucagon-like peptide (GLP-1 & 2) peptide Y (PYY) oxyntomodulin K cell - gastric inhibitory polypeptide/GIP N cell - neurotensin M? cell - motilin D cell (antral) - somatostatin Coordinated with extrinsic & intrinsic neural controls and interacting amongst themselves EC cell - serotonin A cell - ghrelin
  • 110. 110 EXOCRINE PANCREAS Controls Duodenum Exocrine aciniEnteroendocrine cells Secretin & CCK digestive enzymes HCO3 - ions RESPONSE Acid Fats Peptides STIMULI CONTROLLER + Vagal cholinergic control
  • 111. 111 SOURCES OF ‘GUT’ HORMONES RECTUM LIVER PANCREAS GALL BLADDER STOMACH SMALL GUT LARGE GUT Bile gastrin ghrelin Duodenum cholecystokinin motilin somatostatin neurotensin GIP-1 GLP-1&2 Peptide Y insulin glucagon PPY somatostatin secretin Oxyntomodulin
  • 112. 112 SOURCES OF ‘GUT’ HORMONES PANCREAS STOMACH SMALL GUT LARGE GUT gastrin ghrelin Duodenum cholecystokinin motilin somatostatin neurotensin GIP-1 GLP-1&2 Peptide Y insulin glucagon PPY somatostatin secretin Oxyntomodulin
  • 113. 113 Enteroendocrine cell types III Immunostaining for the peptide or chromogranin and fluorescence methods for the amine derivatives now provide clear identification of the cells, but against a background of the old silver-based cell nomenclature A messy story*, because of the various staining reactions of enteroendocrine cells (particularly with silver methods) based on the peptide hormones, the associated chromogranin storage protein in the granules, and any catecholamine, serotonin or histamine content. ECL cell - EnteroChromaffin-Like cell
  • 114. 114 Adipocyte hormones & other metabolic players RECTUM LARGE GUT LIVER SMALL GUT STOMACH PANCREAS GALL BLADDER E S O P H A G U S MOUTH APPENDI X SALIVARY GLAND AIRWAY HYPOTHALAMUS Appetites Homeostasis Emotion CEREBRAL CORTEX Cerebellum Pons Mid- brain Medulla PITUITARY TALUS CALCANEUS Metatarsa l FEMUR Fat cell Adipocytes MUSCLE
  • 115. 115 Adipocyte hormones - LIVER HYPOTHALAMUS TALUS CALCANEUS Metatarsa l FEMUR Fat cell Adipocytes MUSCLE LEPTIN ADIPONECTIN for energy balance and glucose homeostasis
  • 116. 116 Visceral/abdominal fat & type II diabetes, etc LIVER HYPOTHALAMUS TALUS CALCANEUS Metatarsa l FEMUR Fat cell Adipocytes MUSCLE LEPTIN ADIPONECTIN MACROPHAGES(MΦs) Macrophages accumulate in the stroma of the fatty tissue, become activated to release abnormal cytokines , e.g., TNF- α ,that disrupt many metabolic pathways so that the visceral adipose tissue is permanently inflamed and dangerous, e.g. Adipocyte production of adiponectin falls Insulin signalling goes bad, etc.
  • 117. 117 TESTIS & LEYDIG CELLS Peritubular myoid cells LEYDIG INTERSTITIAL CELLS Acidophil Much smooth ER Lipid droplets Crystals of Reinke SERTOLI CELLS Sperm layered SPERMATOGENIC CELLS {stratified germinal epithelium BASAL LAMINA SEMINIFEROUS TUBULE SEMINIFEROUS TUBULE