The document discusses the endocrine system, which regulates homeostasis through the secretion of hormones directly into the bloodstream. It describes the major endocrine glands and hormones, including the hypothalamus and pituitary gland which regulate other glands. The hormones act on target cells through various mechanisms, such as binding to intracellular receptors to activate genes or binding to cell surface receptors and triggering secondary messengers like cAMP. The endocrine system works in tandem with the nervous system to coordinate bodily functions.

2. The Endocrine System
Hormones are conventionally defined as
organic substances, produced in small
amounts by specific tissues (endocrine
glands), secreted into the blood stream to
control the metabolic and biological activities
in the target
cells.
Hormones may be regarded as the
chemical messengers involved in the
transmission of information from one tissue
to another and from cell to cell.
The major endocrine organs in human
body are depicted in fig:

3. Endocrine system maintains
homeostasis
The concept that hormones acting on distant
target cells to maintain the stability of the internal
milieu is a major advance in physiological &
biochemical understanding.
The secretion of the hormone is evoked by a
change in the milieu and the resulting action on
the target cell restores the milieu to normal;
leading to the maintenance of homeostasis

4. Sensing and signaling
Endocrine “glands”
synthesize and store
hormones. These glands
have a sensing and
signaling system which
regulate the duration and
magnitude of hormone
release via feedback from
the target cell.

5. Endocrine vs. Nervous System
• Major communication systems in the body
• Integrate stimuli and responses to
changes in external and internal
environment
• Both are crucial to coordinated functions of
highly differentiated cells, tissues and
organs
• Unlike the nervous system, the endocrine
system is anatomically discontinuous.

6. •The nervous system exerts point-to-point control
through nerves, similar to sending messages by
conventional telephone. Nervous control is
electrical in nature and fast.
•The endocrine system broadcasts its
hormonal messages to essentially all cells by
secretion into blood and extra cellular fluid.
Like a radio broadcast, it requires a receiver
to get the message - in the case of endocrine
messages, cells must bear a receptor for the
hormone being broadcast in order to respond.

7. A cell is a target because it has a specific
receptor for the hormone
Most hormones circulate in blood, coming into contact with essentially
all cells. However, a given hormone usually affects only a limited
number of cells, which are called target cells. A target cell responds
to a hormone because it bears receptors for the hormone.

8. Number of Receptors
• Down-regulation: is the decrease of
hormone receptors which decreases the
sensitivity to that hormone
• Up-regulation: is the increase in the
number of receptors which causes the
cell to be more sensitive to a particular
hormone

9. Functions of Endocrine System
• Controls the processes involved in movement and physiological /
biochemical equilibrium
• Includes all tissues or glands that secrete hormones into the blood
• Secretion of most hormones is regulated by a negative feedback
system
• The number of receptors for a specific hormone can be altered to
meet the body’s demand
• Maintenance of the internal environment in the body (maintaining
the optimum biochemical environment).
• Integration and regulation of growth and development.
• Control, maintenance and instigation of sexual reproduction,
including gametogenesis, coitus, fertilization, fetal growth,
development and nourishment of the newborn.

10. Types of cell-to-cell signaling
Classic endocrine hormones
travel via bloodstream to
target cells; neurohormones
are released via synapses and
travel via the bloostream;
paracrine hormones act on
adjacent cells and autocrine
hormones are released and
act on the cell that secreted
them. Also, intracrine
hormones act within the cell
that produces them.

11. Response vs. distance traveled
Endocrine action: the hormone is distributed in blood and binds to
distant target cells.
Paracrine action: the hormone acts locally by diffusing from its
source to target cells in the neighborhood.
Autocrine action: the hormone acts on the same cell that produced it.

12. Major hormones and systems
• Top down organization of endocrine system.
• Hypothalamus produces releasing factors that stimulate
production of anterior pituitary hormone which act on
peripheral endocrine gland to stimulate release of third
hormone
– Specific examples to follow
• Posterior pituitary hormones are synthesized in neuronal
cell bodies in the hypothalamus and are released via
synapses in posterior pituitary.
– Oxytocin and antidiuretic hormone (ADH)

13. Range from 3 amino acids to hundreds of
amino acids in size.
Often produced as larger molecular weight
precursors that are proteolytically cleaved
to the active form of the hormone.
Peptide/protein hormones are water
soluble.
Comprise the largest number of
hormones– perhaps in thousands
Peptide/protein hormones

14. • Are encoded by a specific gene which is transcribed into
mRNA and translated into a protein precursor called a
preprohormone
• Preprohormones are often post-translationally modified
in the ER to contain carbohydrates (glycosylation)
• Preprohormones contain signal peptides (hydrophobic
amino acids) which targets them to the golgi where
signal sequence is removed to form prohormone
• Prohormone is processed into active hormone and
packaged into secretory vessicles

15. • Secretory vesicles move to plasma membrane where
they await a signal. Then they are exocytosed and
secreted into blood stream
• In some cases the prohormone is secreted and
converted in the extracellular fluid into the active
hormone: an example is angiotensin is secreted by liver
and converted into active form by enzymes secreted by
kidney and lung

16. Peptide/protein hormone synthesis

17. Chemical Classification of Hormones
• Steroid Hormones:
– Lipid soluble
– Diffuse through cell membranes
The Endocrine organs include:
• Adrenal cortex
• Ovaries
• Testes
• placenta

18. • Nonsteroid Hormones:
– Not lipid soluble
– Received by receptors external to the cell membrane
These include:
– Peptides and proteins
– Amino acid derivatives
– Fatty acid derivatives - Eicosanoids
The Endocrine organs include
• Thyroid gland
• Parathyroid gland
• Adrenal medulla
• Pituitary gland
• pancreas

19. Chemical diversity of hormones

20. Classification based on mechanism of action
Group I. Hormones that bind to intracellular receptors
Hormones Origin Major Functions

21. Group II. Hormones that bind to cell surface receptors
A. The second messenger is cAMP
Hormones Origin Major Functions

22. Hormones Origin Major Functions
Grp. II. B. The Second Messenger is Phosphatidyl Inositol / Calcium
Group II. C. The Second Messenger is cGMP
 Atrial natriuretic cardiac diuresis, vasodilation, ms. relaxation
factor (ANF) atrial tissue inhibition of aldosterone secretion
 Nitric oxide (NO) arginine vasodilation, smooth ms.relaxation,
regulation of BP, neurotransmitter

23. Hormones Origin Major Functions
Group II. D. The Second Messenger is Kinase/phosphatase or
unknown / Unsettled

24. General features of hormone classes

25. Hormone Actions
• “Lock and Key” approach: describes the
interaction between the hormone and its
specific receptor.
– Receptors for non-steroid hormones are
located on the cell membrane
– Receptors for steroid hormones are found in
the cell’s cytoplasm or in its nucleus

26. • Steroid Hormones
– Pass through the cell membrane
– Binds to specific receptors
– Then enters the nucleus to bind with the
cells DNA which then activates certain
genes (Direct gene activation).
– mRNA is synthesized in the nucleus and
enters the cytoplasm and promotes protein
synthesis for:
• Enzymes as catalysts
• Tissue growth and repair
• Regulate enzyme function

27. Mechanism of action of steroid hormones

28. • Non-steroid Hormones
– React with specific receptors outside the cell
– This triggers an enzyme reaction with lead to the
formation of a second messenger (cAMP).
– cAMP can produce specific intracellular functions:
• Activates cell enzymes
• Change in membrane permeability
• Promote protein synthesis
• Change in cell metabolism
• Stimulation of cell secretions

29. cAMP in glycogenolysis (phosphorylation)

30. cAMP in glycogen synthesis (glycogenesis)
Dephosphorylation
Similar action of cGMP from GTP

31. cAMP in Lipolysis
+ promoting effect
- inhibiting effect

32. Synthesis and degradation of cAMP

33. G. Proteins: Types & Functions

34. The Endocrine Systems
• The Pituitary Gland is
divided into 2 areas,
which differ
– structurally and
functionally
– each area has
separate types of
hormone production.
– Anterior Pituitary:
• produces thyroid-
stimulating hormone
(TSH)
• growth hormone (GH)
• adrenocorticotropin
(ACTH)
• follicle-stimulating
hormone (FSH)
• Leutinizing (LH)
• Prolactin (PRL)
– The two segments are:
• Posterior Pituitary:
– produces oxytocin
and antidiuretic
hormone (ADH)

35. Overview of pituitary gland

36. Hormonal Heirarchy Relationships

37. • Pituitary Gland
– A marble-sized gland at the base of the brain
– Controlled by the hypothalamus or other neural
mechanisms and therefore the middle man.
• Posterior Lobe
– Antidiuretic hormone: responsible for fluid
retention
– Oxytocin: contraction of the uterus
Oxytocin
ADH

38. Comparison between
ADH & Insulin deficiency Diabetes
Diabetes Mellitus Diabetes Inspidus
 Mellitus means sweet inspidus means tasteless.
 Insulin deficiency ADH deficiency
 Polyuria moderate polyuria severe
 Urine sp. gravity↑ specific gravity↓
 Hyperglycemia Blood glucose normal
 Urine benedict test +ve Benedict test negative

39. Exercise appears to be a strong stimulant to the
hypothalamus for the release of all anterior
pituitary hormones.
Hypothalamic hormones:
TRH, CRH, GnRH, GRH, GRIH, PRIH
• Pituitary Gland
• Master Endocrine Gland (Chairman)
• ADENOHYPOPHYSIS: catagorized as
• GH-PROLACTIN GROUP: growth hormone, Prolactin
• GLYCOPROTIN HORMONES: TSH, LH, FSH, HCG?
• POMC PEPTIDE FAMILY : ACTH, LPH?, endorphin?

40. Main actions of ACTH
 Effects on adrenal cortex :-
i. Increases synthesis and release of adrenocorticoids
ii. Increases adrenal cortical growth (trophic effect).
iii. ↑production leads to ↑glucose & cushing syndrome.
iv. Lowers contents of vit.C of adrenal cortex.
v. Lowers cholesterol of adrenal cortex.
 Extra adrenal effects of ACTH:-
i. Release of free fatty acids from fats.
ii. Slight diabetogenic action.
iii. Release of insulin.
iv. Decreased deamination of amino acids.
v. Liberation of histamine.
vi. Pigmentation of the skin.

41. Main actions of Growth Hormone
 Protein synthesis
 Hyperglycemia
 Lipolysis
 ↑rate of growth
 Retention of Ca, P, Mg, Na, K, CI.
Growth Hormone disorders
1. Panhypopitutarism:↓GH, ↓growth →dawarfism.
2. Hyperpituitarism with excessive GH production:
a) Gigantism (before puberty)
b) Acromegaly (in adult age)

42. Pro-opiomelanocortin (POMC) family members
ACTH-Adrenocorticotropic Hormone
LPH-Lipotropin,
MSH-Melanocyte stimulating hormone
CLIP-Corticotropin like intermediate lobe peptide

43. Amine hormones
There are two groups of hormones derived from
the amino acid tyrosine
Thyroid hormones and Catecholamines

44. • Two other amino acids are used for
synthesis of hormones:
• Tryptophan is the precursor to serotonin
and the pineal hormone melatonin
• Glutamic acid is converted to histamine

45. • The Thyroid Gland
– lies in the anterior neck
just below the larynyx.
– Two lobes, located on
either side of the
trachea, connected by a
narrow band of tissue
called the isthmus.
– Sacs inside the gland
contain colloid
• Within the colloid are
the thyroid hormones:
– thyroxine (T4)
– triiodothyronine (T3)
• When stimulated
(by TSH or by
cold), these are
released into the
circulatory system
and  the
metabolic rate.
– “C” cells within the
thyroid produce the
hormone calcitonin.

46. Structures of Thyroid Hormones

47. Thyroid Hormone
 Thyroid hormones are basically a "double" tyrosine
with the critical incorporation of 3 or 4 iodine atoms.
 Thyroid hormone is produced by the thyroid
gland and is lipid soluble
 Thyroid hormones are produced by modification of a
tyrosine residue contained in thyroglobulin, post-
translationally modified to bind iodine, then
proteolytically cleaved and released as T4 and T3.
T3 and T4 then bind to thyroxin binding globulin for
transport in the blood

48. Biosynthesis of Thyroid Hormones

50. Overview of Regulation
& functions of
Thyroid Hormones

51. • Thyroid Gland
– Located along the midline of the neck
– Secretes two nonsteroid hormones
• Triiodothyronine (T3)
• Thyroxine (T4)
– Regulates metabolism
• increases protein synthesis
• promotes glycolysis, gluconeogenesis, glucose
uptake
• Calcitonin: calcium metabolism
• when released, lowers the amount of calcium in the
blood.

52. • Disorders of hypothyroidism.
 In infants Cretinism:
Growth & mental retardation.
 In adults Myxedema:
Low BMR, sensitivity to cold,
slow heart rate,, slowing of all intellectual functions,
dry skin & hair, hypercholesterolemia,
sluggish behaviour.

53. • Increased thyroid hormone
release causes
hyperthyroidism, commonly
called Graves’ disease.
– Signs and symptoms:
• insomnia, fatigue
• tachycardia
• hypertension
• heat intolerance
• weight loss
• ↑BMR, moist skin
• Fine tremors
• ↓B.Wt, hypocholesteremia
– Long term
hyperthyroidism:
• Exopthalmos
– bulging of the
eyeballs (picture
Barbara Bush)
– ↑LATS/TSI,
– ↑T3 & T4
• In severe cases - a
medical emergency
called thyrotoxicosis
can result.

54. • Parathyroid Glands
– small, pea-shaped
glands, located in the
neck near the thyroid
– usually 4 - number can
vary
– Regulate the level of
calcium in the body
– Regulates phosphate
levels
– produce parathyroid
hormone (PTH) -
 level of calcium in
blood by osteoclast
activity through cAMP
– Hypocalcemia can
result if parathyroids
are removed or
destroyed.

55. • Adrenal Glands
– 2 small glands that sit atop
both kidneys.
– Each has 2 divisions, each
with different functions.
– Catecholamines:
• Epinephrine: elicits a fight
or flight response
• Increase H.R. and B.P.
• Increase respiration
• Increase metabolic rate
• Increase glycogenolysis
• Lipolysis
• Vasoconstriction
• Dilation of bronchioles
• Norepinephrine
House keeping system
A. The Adrenal Medulla
secretes the catecholamine
hormones norepinephrine
and epinephrine (closely
related to the sympathetic
component of the autonomic
nervous system).
B. Adrenal cortex secrets
Adrenocorticosteroids

56. Catecholamine hormones
 Catecholamines are both neurohormones and
neurotransmitters.
 These include epinephrine, and norepinephrine
 Epinephrine and norepinephrine are produced by the
adrenal medulla both are water soluble
 Secreted like peptide hormones

57. Synthesis of catecholamines

59. • Essential role of adrenaline in emergencies
 Increases body capabilities in stressful conditions :
 Raises blood glucose for energy (glycogenolysis).
 Increases FFA level for energy (lipolysis)
 ↑cardiac output, ↑BP, ↑ blood supply to muscle.
 ↑breathing capacity; ↑ rate and depth of respiration.
 Contract spleen to add more RBCs to circulation.

60. • Pheochromocytoma
 It is tumor of adrenal medulla causing
hypersecretion of catecholamines. It is
diagnosed by -
 Signs-symptoms : palpitation, tremors,
headache etc.
 Raised BP. (hypertension: paroxysmal or
persistent).
 Raised glucose hyperglycemia and glycosuria.
 Raised levels of plasma catecholamines
 ↑Urine excretion of VMA and catecholamines

61. Pancreas Gland
– a key gland located in
the folds of the
duodenum
– has both endocrine
and exocrine functions
– secretes several key
digestive enzymes
• Islets of Langerhans
– specialized tissues in
which the endocrine
functions of the
pancreas occurs
• include 3 types of
cells:
• alpha ( )
• beta ()
• delta ()
• f- Cells
• each secretes an
important hormone.

62. • Alpha () cells
release glucagon,
essential for
controlling blood
glucose levels.
• When blood glucose
levels fall,  cells 
the amount of
glucagon in the blood
.
• The surge of
glucagon stimulates
the liver to release
glucose stores (from
glycogen and
additional storage
sites).
• Also, glucagon
stimulates the liver to
manufacture glucose
by gluconeogenesis.

63. • Beta Cells () release
insulin (antagonistic to
glucagon).
• Insulin  the rate at
which various body cells
take up glucose. Thus,
insulin lowers the blood
glucose level
(Hypoglycemic).
• Insulin is rapidly broken
down by the liver by
insulinase and must be
secreted constantly.
• Delta Cells () produce
somatostatin, which
inhibits both glucagon
and insulin.
• f- Cells-- Polypeptide

64. Main actions of insulin and glucagon
Insulin Glucaqon
a) Anabolic catabolic
b) Hypoglycemic hyperglycemic
c) Glycogenesis glycogenolysis
d) ↓Gluconeogenesis ↑gluconeogenesis
e) ↑ GIycolysis ↓glycolysis
f) Protein synthesis proteolysis
g) Lipogenesis lipolysis
h) ↓Ketogenesis ↑ketogenesis
i) Nucleic acid synthesis urea synthesis.

65. Human proinsulin, insulin & C-peptide

66. Mechanism of
insulin action
IRS=
Insulin receptor substrate

67. insulin-dependent tissues for
glucose metabolism
Adipose tissue, Skeletal muscle, Liver.
Liver cells require insulin for glucose metabolism not for
glucose transport through cells.
insulin-independent tissues for
glucose uptake
Brain, liver, RBCs, WBCs, intestinal mucosa,
cornea, lens of eyes & renal tubules.
The word NSILA stands
Non-suppressible insulin like activity (somatomedin).

68. Glucose Homeostasis
Blood Glucose
Fastin 70-100 mg/dl
Post-prandial 110-126mg/dl

69. Comparison B/W types of D.M

70. • Main complaints of a diabetic person
In early stage of disease:
Polyuria, polydipsia, polyphagia.
In late stage patient develops:
body pains, weight loss, generalized weakness,
neuropathy (burning feet), nephropathy (albuminuria),
retinopathy and cataract in early age.
• Common tests for diabetes mellitus
Routine laboratory tests for diagnosis for DM. are :-
a) Urine test for sugar: +ve from green to red ppt.
b) Fasting blood glucose : >140 mg/dl confirms DM.
c) Random or 2 hrs glucose: >200 mg/dl confirms DM.
d) GTT is done to confirm if above tests are disputed.
e) HbA 1c estimation for DM management

71. Oral GTT

72. Glycosuria& its causes.
Glycos-sweet, uria-urine. It means presence of sugar in urine.
Normally sugar is not present in urine.
Causes are:
a) Diabetes mellitus
b) Renal glycosuria (renal threshold)
c) Alimentary
d) In pregnancy
e) Emotional glycosuria.
Glycosylated Hb(HbA 1c) & its significance.
Glycosylated Hb (HbA1c) is formed by post-synthetic interaction
between Hb and glucose, whereby glucose is attached to the N-
terminal amino group of beta-chain by a ketoamine linkage. The
normal levels range 3—6 gm% but increase 2—3 fold in
uncontrolled diabetes mellitus. HbAtc is utmost help for monitoring
the glycemic control of diabetic patients.

73. All steroid hormones are derived from
cholesterol and differ only in the ring
structure and side chains attached to it.
All steroid hormones are lipid soluble
Steroid hormones

74. The Endocrine Glands
• Adrenal Cortex
• Secretes over 30 different steroid hormones
(corticosteroids)
– Mineralocorticoids
• Aldosterone: maintains electrolyte balance
– Glucocorticoids
• Cortisol:
– Stimulates gluconeogenisis
– Mobilization of free fatty acids
– Glucose sparing
– Anti-inflammatory agent
– Gonadocorticoids
• testosterone, estrogen, progesterone

75. Types of steroid hormones
• Glucocorticoids; cortisol is the major
representative in most mammals
• Mineralocorticoids; aldosterone being
most prominent
• Androgens such as testosterone
• Estrogens, including estradiol and
estrone
• Progestogens (also known a progestins)
such as progesterone

76. The Endocrine System
• The Adrenal Cortex
secretes 3 classes
of hormones, all
steroid hormones:
– gluticocorticoids
mineralocorticoids
– androgenic hormones
• One at a time…
– gluticocorticoids:
– accounts for 95% of
adrenal cortex
hormone production
–  the level of glucose
in the blood
– Released in
response to stress,
injury, or serious
infection - like the
hormones from the
adrenal medulla.

77. The Endocrine System
• Mineralocorticoids:
– work to regulate the
concentration of
potassium and sodium
in the body.
• Prolonged  in
adrenal cortex
hormone results in
Cushing’s Disease.
• Signs & Symptoms of
Cushing’s Disease:
–  in blood sugar
levels
– unusual body fat
distribution
– rapid mood swings

78. The Endocrine System
• And - if there is an 
in
mineralocorticoids
as well
– A serious electolyte
imbalance will occur
due to the  potassium
excretion by the
kidney, which results
in hypokalemia.
• Sodium can also be
retained by the
kidney, resulting in
hyponatremia.
– Causes:
• dysrhythmias
• coma
• death
– usually results from a
tumor - TX?
Removal of tumor.

79. The Endocrine System
• Gonads and
Ovaries:
– the endocrine glands
associated with human
reproduction.
– Female ovaries
produce eggs
– Male gonads produce
sperm
• both have endocrine
functions.
• Ovaries:
– located in the
abdominal cavity
adjacent to the uterus.
– Under the control of
LH and FSH from the
anterior pituitary they
manufacture
• estrogen
• protesterone

80. The Endocrine System
• Estrogen and
Progesterone have
several functions,
including sexual
development and
preparation of the
uterus for
implantation of the
egg.
• Testes:
– located in the scrotum
– produce sperm for
reproduction
– manufacture
testosterone -
• promotes male
growth and
masculinization
– Controlled by anterior
pituitary hormones
FSH and LH.

81. Steroid hormones
• Are not packaged, but synthesized and
immediately released
• Are all derived from the same parent compound:
Cholesterol
• Enzymes which produce steroid hormones from
cholesterol are located in mitochondria and
smooth ER
• Steroids are lipid soluble and thus are freely
permeable to membranes so are not stored in
cells

82. Steroid hormones
• Steroid hormones are not water soluble so have
to be carried in the blood complexed to specific
binding globulins.
• Corticosteroid binding globulin carries cortisol
• Sex steroid binding globulin carries testosterone
and estradiol
• In some cases a steroid is secreted by one cell
and is converted to the active steroid by the
target cell: an example is androgen which
secreted by the gonad and converted into
estrogen in the brain

83. Steroids can be transformed to
active steroid in target cell

84. Steroidogenic Enzymes
Common name "Old" name Current name
Side-chain cleavage enzyme;
desmolase
P450SCC CYP11A1
3 beta-hydroxysteroid
dehydrogenase
3 beta-HSD 3 beta-HSD
17 alpha-hydroxylase/17,20 lyase P450C17 CYP17
21-hydroxylase P450C21 CYP21A2
11 beta-hydroxylase P450C11 CYP11B1
Aldosterone synthase P450C11AS CYP11B2
Aromatase P450aro CYP19

86. Steroid hormone synthesis
All steroid hormones are derived from cholesterol.
A series of enzymatic steps in the mitochondria
and ER of steroidogenic tissues convert
cholesterol into all of the other steroid hormones
and intermediates.
The rate-limiting step in this process is the
transport of free cholesterol from the cytoplasm
into mitochondria. This step is carried out by the
Steroidogenic Acute Regulatory Protein (StAR)

87. Steroid hormone synthesis
•The cholesterol precursor comes from cholesterol
synthesized within the cell from acetate, from
cholesterol ester stores in intracellular lipid
droplets or from uptake of cholesterol-containing
low density lipoproteins.
•Lipoproteins taken up from plasma are most
important when steroidogenic cells are chronically
stimulated.

88. cholesterol
Extracellular
lipoprotein
Cholesterol
pool
LH
ATP
cAMP
PKA+
Pregnenolone
Progesterone
Androstenedione
TESTOSTERONE
3HSD
P450c17
17HSD
acetate

89. 1,25-dihydroxy Vitamin D3 is also derived
from cholesterol and is lipid soluble
Not really a “vitamin” as it can be
synthesized de novo
Acts as a true hormone
1,25-Dihydroxy Vitamin D3

90. Fatty Acid Derivatives -
Eicosanoids
• Arachadonic acid is the most abundant
precursor for these hormones. Stores of
arachadonic acid are present in membrane lipids
and released through the action of various
lipases. The specific eicosanoids synthesized by
a cell are dictated by the battery of processing
enzymes expressed in that cell.
• These hormones are rapidly inactivated by being
metabolized, and are typically active for only a
few seconds.

91. Fatty Acid Derivatives -
Eicosanoids
• Eicosanoids are a large group of
molecules derived from polyunsaturated
fatty acids.
• The principal groups of hormones of this
class are prostaglandins, prostacyclins,
leukotrienes and thromboxanes.

92. The Endocrine Glands
• Gonads
– testes (testosterone) = sex characteristics
• muscle development and maturity
– ovaries (estrogen) = sex characteristics
• maturity and coordination
• Kidneys (erythropoietin)
– regulates red blood cell production

93. Regulation of hormone
secretion
 Sensing and signaling: a biological need is
sensed, the endocrine system sends out a signal
to a target cell whose action addresses the
biological need. Key features of this stimulus
response system are:
 receipt of stimulus
 synthesis and secretion of hormone
 delivery of hormone to target cell
 evoking target cell response
 degradation of hormone

94. Control of Endocrine Activity
•The physiologic effects of hormones depend
largely on their concentration in blood and
extracellular fluid.
•Almost inevitably, disease results when hormone
concentrations are either too high or too low, and
precise control over circulating concentrations of
hormones is therefore crucial.

95. Control of Endocrine Activity
The concentration of hormone as seen by target
cells is determined by three factors:
•Rate of production
•Rate of delivery
•Rate of degradation and elimination

96. Control of Endocrine Activity
Rate of production: Synthesis and secretion of
hormones are the most highly regulated aspect of
endocrine control. Such control is mediated by
positive and negative feedback circuits, as described
below in more detail.

97. Control of Endocrine Activity
Rate of delivery: An example of this effect is
blood flow to a target organ or group of target
cells - high blood flow delivers more hormone
than low blood flow.

98. Control of Endocrine Activity
Rate of degradation and elimination: Hormones,
like all biomolecules, have characteristic rates of
decay, and are metabolized and excreted from the
body through several routes.
Shutting off secretion of a hormone that has a very
short half-life causes circulating hormone
concentration to plummet, but if a hormone's
biological half-life is long, effective concentrations
persist for some time after secretion ceases.

99. Feedback Control of Hormone
Production
Feedback loops are used
extensively to regulate
secretion of hormones in the
hypothalamic-pituitary axis.
An important example of a
negative feedback loop is seen
in control of thyroid hormone
secretion

100. Negative Feedback
• Negative feedback is the primary
mechanism through which your
endocrine system maintains homeostasis
• Secretion of a specific hormone s turned
on or off by specific physiological
changes (similar to a thermostat)
• EXAMPLE: plasma glucose levels and
insulin response

101. Inputs to endocrine cells

102. Neural control
• Neural input to hypothalamus stimulates
synthesis and secretion of releasing
factors which stimulate pituitary hormone
production and release

103. Chronotropic control
• Endogenous neuronal rhythmicity
• Diurnal rhythms, circadian rhythms
(growth hormone and cortisol), Sleep-
wake cycle; seasonal rhythm

104. Episodic secretion of hormones
• Response-stimulus coupling enables the
endocrine system to remain responsive to
physiological demands
• Secretory episodes occur with different
periodicity
• Pulses can be as frequent as every 5-10
minutes

105. • The most prominent episodes of release occur
with a frequency of about one hour—referred to
as circhoral
• An episode of release longer than an hour, but
less than 24 hours, the rhythm is referred to as
ultradian
• If the periodicity is approximately 24 hours, the
rhythm is referred to as circadian
– usually referred to as diurnal because the increase in
secretory activity happens at a defined period of the
day.
Episodic secretion of hormones

106. Circadian (chronotropic) control

107. Circadian Clock

108. Physiological importance of
pulsatile hormone release
• Demonstrated by GnRH infusion
• If given once hourly, gonadotropin secretion and
gonadal function are maintained normally
• A slower frequency won’t maintain gonad
function
• Faster, or continuous infusion inhibits
gonadotropin secretion and blocks gonadal
steroid production

109. Clinical correlate
• Long-acting GnRH analogs (such as
leuproline) have been applied to the
treatment of precocious puberty, to
manipulate reproductive cycles (used in
IVF), for the treatment of endometriosis,
PCOS, uterine leiomyoma etc

110. Feedback control
• Negative feedback is most common: for
example, LH from pituitary stimulates the testis
to produce testosterone which in turn feeds back
and inhibits LH secretion
• Positive feedback is less common: examples
include LH stimulation of estrogen which
stimulates LH surge at ovulation

111. Negative feedback effects of cortisol

112. Substrate-hormone control
• Glucose and insulin: as glucose increases
it stimulates the pancreas to secrete
insulin

113. Feedback control of insulin by
glucose concentrations

114. The Endocrine Response to
Exercise

115. Regulation of Glucose Metabolism
During Exercise
• Glucagon secretion increases during exercise
to promote liver glycogen breakdown
(glycogenolysis)
• Epinephrine and Norepinephrine further
increase glycogenolysis
• Cortisol levels also increase during exercise for
protein catabolism for later gluconeogenesis.
• Growth Hormone mobilizes free fatty acids
• Thyroxine promotes glucose catabolism

116. Hormonal Effects on Fluid and
Electrolyte Balance
• Reduced plasma volume leads to release of
aldosterone which increases Na+ and H2O
reabsorption by the kidneys and renal
tubes.
• Antidiuretic Hormone (ADH) is released
from the posterior pituitary when
dehydration is sensed by osmoreceptors,
and water is then reabsorbed by the
kidneys.

117. The Endocrine System
• Endocrine
Emergencies:
• Diabetes Mellitus
– one of the most
common diseases in
North America.
–  insulin secretion
by the Beta () cells
of the islets of
Langerhans in the
pancreas.
• Complications of
Diabetes:
– contributes to heart
disease
– stroke
– kidney disease
– blindness

118. The Endocrine System
• Pathophysiology of
Diabetes:
• Glucose Metabolism
– Glucose (dextrose) is
a simple sugar
required by the body
to produce energy.
– Sugars, or
carbohydrates, are 1
of 3 major food
sources used by the
body.
• The other 2 major
food sources are
– proteins
– fats
• Most sugars in the
human diet are
complex and must be
broken down into
simple sugars:
glucose, galactose
and fructose - before
use.

119. The Endocrine System
• Breakdown of sugars
is carried out by
enzymes in the gastro
intestinal system.
– As simple sugars,
these are absorbed
from the GE system
into the body.
– More than 95% enter
the body as glucose.
• To be converted into
energy, glucose must
first be transmitted
through the cell
membrane. BUT -
the glucose molecule
is large and doesn’t
readily diffuse through
the cell membrane.

120. The Endocrine System
• Glucose must pass
into the cell by
binding to a special
carrier protein on the
cell’s surface.
– Facilitated diffusion -
doesn’t use energy.
The carrier protein
binds with the glucose
and carries it into the
cell.
• The rate at which
glucose can enter the
cell is dependent
upon insulin levels.
– Insulin serves as the
messenger - travels
via blood to target
tissues.
– Combines with specific
insulin receptors on
the surface of the cell
membrane.