hypothalamus and pituitary

1. Hypothalamus & Pituitary
Lecture number 1
Endocrinology module
Dr Sadia Haroon
Department of biochemistry

2. YEAR second MBBS
SERIAL NUMBER 187
MODULE ENDOCRINE MODULE
TEACHER DR.SADIA HAROON
DEPARTMENT OF
BIOCHEMISTRY
DATE 1.9.2020
KEY WORD HYPOTHALAMUS AND
PITUITARY GLAND 2

3. LEARNING OBJECTIVES
• To know functions of hypothalamus
• The releasing and inhibiting factors secreted
by hypothalamus
• Clinical uses
• Pituitary hormones and their relation with
hypothalamus

4. Home work
• Write functions of hypothalamus related to
endocrine system.
• Enumerate releasing factors and inhibiting
factor from hypothalamus .
• What are trophic hormones of pituitary and
their fuctions.
• Enumerate functions of pituitary gland .

5. Write note on
• Comparison of ant and post pituitary .
• Somatostatin
• Prolactin and its control
• POMC
• Function of MSH.
• panhypopitiutrism

6. Hypothalamus

7. Hypothalamus
• Synthesizes releasing hormones in cell bodies of
neurons
• Hormones are transported down the axon and
stored in the nerve endings
• Hormones are released in pulses

9. Trophic
hormones

11. Hypothalamic Releasing Hormones
Seven releasing hormones are made in the
hypothalamus
– Thyrotropin-releasing hormone (TRH)
– Corticotropin-releasing hormone (CRH)
– Gonadotropin-releasing hormone (GnRH)
– Growth hormone-releasing hormone (GHRH)
– Growth hormone-release inhibiting hormone (GHIH)
– Prolactin-releasing factor (PRF)
– Prolactin-inhibiting hormone (PIH)

13. Where & what is the hypothalamus?

14. Anatomical Relations
• Pituitary
• Sella Turcica
• Optic Chiasm
• Median Eminence
• Mamillary Body
• Cavernous Sinus (not
visible)

15. Figure 11-3:Autonomic control centers in the brain

18. Hypothalamus
• Integrates functions that maintain chemical
and temperature homeostasis
• Functions with the limbic system
• Controls the release of hormones from the
anterior and posterior pituitary

19. How does the neuroendocrine axis work?
• Hypothalamic parvicellular neurons synthesize release- or
release-inhibiting “factors” or “hormones” (peptides)
• Packaged in secretory granules, transported in axons to nerve
terminal storage sites
• On demand, neurons depolarize, prompting frequency-
dependent exocytosis into the median eminence capillaries of
the pituitary portal vessels
• Transported as “hormones” to the anterior pituitary where
they exit to the extracellular space
• Attach to specific G-protein coupled receptors on target cells,
triggering exocytosis of appropriate “hormones” that seek their
peripheral glandular targets

20. Hypothalamic hormones
The pulsatile nature of hormone release from
the hypothalamus is critical for maintained
optimal responsiveness of the pituitary cells.
-Pulsatile secretion decreases the extent of
down-regulation of pituitary receptors.
-Continuous release of hypothalamic
hormones actually suppresses the secretion of
pituitary hormones.

21. Negative Feedback Controls:
Long & Short Loop Reflexes
Figure 7-15: Control pathway for cortisol secretion

22. Hypothalamus-Pituitary: Anatomy
Hypothalamus: nervous tissue below
thalamus
Pituitary: small outgrowth of the forebrain,
size of half a pea
• Two functional parts
– Adenohypophysis (anterior pituitary)
• Rathke’s pouch – ectoderm above mouth
– Neurohypophysis (posterior pituitary)
• Hypothalamus
• Move together during development

23. © 2013 Pearson Education, Inc.
The Pituitary Gland and
Hypothalamus
• Pituitary gland (hypophysis) has two
major lobes
– Posterior pituitary (lobe)
• Neural tissue
– Anterior pituitary (lobe)
(adenohypophysis)
• Glandular tissue

24. Subdivisions of the Pituitary
(Hypophysis)
• Adenohypophysis
(Anterior Pituitary)
– Pars Distalis
– Pars Intermedia
– Pars Tuberalis
• Neurohypophysis
(Posterior Pituitary)
– Pars Nervosa
– Infundibular Stalk

25. Cells:
• Acidophils
– Somatotroph
– Lactotroph
• Basophils
– Gonadotrophs
– Thyrotrophs
• Corticotrophs
(can’t distinguish)
• Chromophobes

26. Hormones
• Prolactin/Growth Hormone Family
– Prolactin
– Growth Hormone
• Glycoprotein Family
– Thyroid Stimulating Hormone (TSH)
– Gonadotropins:
• Follicle Stimulating Hormone (FSH)
• Luteinizing Hormone (LH)
• Pro-opiomelanocortin Family
– ACTH

27. Hypothalamus-Pituitary:
Blood and nerve supplies
• Hypothalamus
– Hypothalamic neurons release hormones directly into
capillary plexus
• Anterior pituitary
– Blood supply from median eminence of hypothalamus – portal
system
– Hormones from hypothalamus to pituitary
– Sympathetic/parasympathetic nerves
• Posterior pituitary
– Supraoptic and paraventricular nuclei in hypothalamus

28. © 2013 Pearson Education, Inc.
Figure 16.5a The hypothalamus controls release of hormones from the pituitary gland in two different ways (1 of 2).
Slide 1
1 Hypothalamic neurons
synthesize oxytocin or
antidiuretic hormone (ADH).
3Oxytocin and ADH are
stored in axon terminals in
the posterior pituitary.
4When hypothalamic neurons
fire, action potentials arriving at
the axon terminals cause
oxytocin or ADH to be released
into the blood.
Oxytocin
ADH
Posterior lobe
of pituitary
Optic
chiasma
Infundibulum
(connecting stalk)
Hypothalamic-
hypophyseal
tract
Axon terminals
Posterior lobe
of pituitary
Paraventricular nucleus
Hypothalamus
Supraoptic
nucleus
Inferior
hypophyseal
artery
2 Oxytocin and ADH are
transported down the axons of
the hypothalamic- hypophyseal
tract to the posterior pituitary.

29. Figure 16.5b The hypothalamus controls release of hormones from the pituitary gland in two different ways (2 of 2).
Slide 1
Hypothalamic hormones
travel through portal veins to
the anterior pituitary where
they stimulate or inhibit
release of hormones made in
the anterior pituitary.
hormones, the anterior
pituitary secretes hormones
into the secondary capillary
plexus. This in turn empties
into the general circulation.
GH, TSH, ACTH,
FSH, LH, PRL
Anterior lobe
of pituitary
© 2013 Pearson Education, Inc.
portal system
• Primary capillary
plexus
• Hypophyseal
portal veins
• Secondary
capillary plexus
Superior
hypophyseal
artery
Anterior lobe
of pituitary
Hypothalamus Hypothalamic
neurons synthesize
GHRH, GHIH, TRH,
CRH, GnRH, PIH.
A portal
system is
two
capillary
plexuses
(beds)
connected
by veins.
1 When appropriately stimulated,
hypothalamic neurons secrete
releasing or inhibiting hormones
into the primary capillary plexus.
Hypophyseal
2
3 In response to releasing

31. Functions of the HPA

33. Pituitary releasing hormones
• CRH:
• TRH:
• GHRH:
• Somatostatin:
• GnRH:
• Dopamine:
• Vasopressin:
Corticotrophin releasing
hormone (ACTH)
Thyrotrophin releasing
hormone
GH releasing hormone
GH inhibition
Gonadotrophin (LH, FSH)
releasing hormone
Prolactin inhibition
ACTH release

34. Neurotransmitters in the Hypothalamus
The hypothalamus has been referred to as a
“pharmacological museum” by virtue of the plethora of
neurotransmitters that it contains.
The list of putative neurotransmitters includes:
 ACh,
GABA,
glutamate,
serotonin,
dopamine, and
norepinephrine as well as literally dozens of peptides that
have been identified in recent years.

35. © 2013 Pearson Education, Inc.
Anterior Pituitary Hormones
• Growth hormone (GH)
• Thyroid-stimulating hormone (TSH) or
thyrotropin
• Adrenocorticotropic hormone (ACTH)
• Follicle-stimulating hormone (FSH)
• Luteinizing hormone (LH)
• Prolactin (PRL)

36. A ‘global’ view of hypothalamic pituitary
functions

38. Figure 18.1
Hypothalamus: regulator of the endocrine system

39. Figure 18.5
Three Methods of Hypothalamic Control over the Endocrine System

40. Hypothalamic Control of the Anterior
Pituitary
• Hormonal control
mechanism
• Hypothalamic neurons
synthesize releasing and
inhibiting peptide hormones.
• These are transported to
axon endings in the median
eminence where they are
secreted into the
hypothalamo-hypophyseal
portal system to reach
receptors that regulate the
secretions of anterior
pituitary hormones

41. Hypothalamus
releasing
factors/hormones
Stimulates
anterior pituitary
Produce and
secrete tropic
hormones
stimulate target
glands to secrete
hormones
act on target
organ.

42. The Hypothalamus
Neural Influences Hormonal Influences
Endocrine
System
Autonomic
Nervous
System
Limbic
System

43. Functions of the Hypothalamus
Autonomic nervous system regulation
Hormone production
Endocrine regulation
Circadian rhythm regulation
Limbic system interaction
Various
– Temperature regulation
– Feeding
–

44. B GONADOTROPIC
CELL
CA
M
Ca
2+
CAM-
dependent
kinase
Protein
kinase C
Ca2+
Storage
vesicle
L
FSH
PIP
2
P
GnR
H
Gq
3
Ca2
+
Protein
phosphorylation
Figure 6. In the goHnadotropes GnRH causes release of LH
SE
R
Ca2
+
IP
Y
GnRH
recDepAtor
G


q
L q
C

45. In 1–2 weeks they
cause desensitization
and down regulation
of GnRH receptors
inhibition of FSH and
LH secretion
suppression of
gonadal function.
Spermatogenesis or
ovulation cease and
testosterone or
estradiol levels fall to
castration levels.

46. Gonadotropin-releasing hormone (Gnrh):
•Regulates the secretion of gonadotropins—FSH and LH
•Secreted in a pulsatile manner.
•Gonadorelin is synthetic GnRH, used in diagnostic tests in hypogonadism.
•Pulsatile administration is used in infertility and delayed puberty.
•Continuous administration inhibits gonadotropin secretion
• used in prostatic cancers and some gynecological conditions like
uterine fibroids and endometriosis. Ex- leuprolide, Goserelin, Nafarelin,
Triptorelin,

47. GnRH antagonists:
• Some extensively substituted GnRH analogues act as GnRH receptor
antagonists.
•Inhibit Gn secretion without causing initial stimulation.
•They block the pituitary GnRH receptors and thereby suppress the
secretion of LH, FSH and delay ovulation.
•They are used in in vitro fertilization and are also useful in prostatic
cancer
and in reducing uterine fibroids and endometriosis.
Ex- ganirelix and cetrorelix

49. Feedback control
Tropic Hormone
PITUITARY
Short loop
Long loop
HYPOTHALAMUS
XRH XIH
Target Gland
Tropic Hormone
(+ )
Target Hormone
(- )
(-)
(+)
Tropic
Hormone
Stress
STRESS, Metabolic status
Target Hormone
(- )
Long loop

50. Pathologies: Due to Receptors
Figure 7-20: Primary and secondary hypersecretion of cortisol

51. • Hypothalamic stimulation–from CNS
• Pituitary stimulation–from hypothalamic trophic Hs
• Endocrine gland stimulation–from pituitary trophic Hs
Endocrine Control: Three Levels
of Integration

52. Endocrine Control: Three Levels
of Integration
Figure 7-13: Hormones of the hypothalamic-anterior pituitary pathway

53. HYPOTHALAMIC
HORMONE
EFFECTS ON THE
ANTERIOR PITUITARY
Thyrotropin-releasing hormone
(TRH)
Stimulates release of TSH
(thyrotropin) and Prolactin
Corticotropin-releasing hormone
(CRH)
Stimulates release of ACTH
(corticotropin)
Gonadrotropin-releasing
hormone (GnRH)
Stimulates release of FSH and
LH (gonadotropins)
Growth hormone-releasing
hormone (GHRH)
Stimulates release of growth
hormone
Growth hormone-inhibiting
hormone (GHIH)
Inhibits release of growth
hormone
{Prolactin-inhibiting hormone
(PIH)
Stimulates release of prolactin
Prolactin-inhibiting hormone
(PIH)
Inhibits release of prolactin

54. Hypothalamus Releasing Hormones:
Secretion
• Is influenced by emotions
• Can be influenced by the metabolic state of
the individual
• Delivered to the anterior pituitary via the
hypothalamic-hypophyseal portal system
• Usually initiates a three-hormone sequence

55. Feedback control of Endocrine Secretion

56. Feedback control of Endocrine Secretion

57. Pathologies: Over or Under
Production
Figure 7-19: Negative feedback by exogenous cortisol

58. Somatostatin:
It is growth hormone release inhibiting hormone (GHRIH).
•Inhibits secretion of GH, also inhibits thyroid stimulating hormone,
Insulin, prolactin, glucagon.
Uses:
•Use to prevent acute bleeding due to esophageal varices.
•Upper git bleeding from haemorrhagic gastritis, intestinal or
pancreatic fistula.
•Hypersecretory tumour of intestinal tract.
Limitation: short half life, lack of specificity, GH rebound after
discontinuation.

59. Feedback Control of
Anterior Pituitary
• Long Loop
• Short Loop
• Ultrashort Loop
• Amplitude
• Frequency

60. • Stimuli
– Stretch
– Glucose
– Insulin levels
• Reflex
– Lower blood glucose
– Reduces stimulus
– Reduces insulin release
Multiple Stimuli for Hormone
Release:
Nervous & Endocrine

61. Hypothalamo-hypophyseal Portal
System
• Superior hypophyseal
artery
• Portal Vessels
• Capillary Bed of
Pars Distalis

62. Anatomy of the pituitary gland

63. The Hypophyseal
Portal System

64. Anterior pituitary hormones are produced by separate group of cells:
 Somatotrophs: Growth hormones
 Lactotrophs: Prolactin
 Gonadotrophs:
 Corticotrophs:
FSH, LH
ACTH
Intermediate Lobe: Melanocyte stimulatory hormones
Posterior lobe: Vasopressin and Oxytocin
Anterior pituitary hormones are regulated by negative feedback
mechanism.
A long negative feedback loop A short negative feedback loop

65. Prohormones
• Many small hormones, especially peptide
hormones, are synthesized as part of a
larger peptide.
• The large peptide is called a prohormone
• The active hormone is cut out of the larger
prohormone by an enzyme.
• The prohormone generally is not active.

66. POMC

67. POMC
• Proopiomelanocortin (POMC) is the
pituitary precursor of circulating
• melanocyte stimulating hormone (α-MSH)
• , adrenocorticotropin hormone (ACTH),
• and β-endorphin.

68. MSH FUNCTION
• α-MSH. Acting through melanocortin 1
receptor, α-MSH stimulates the production
and release of melanin (a process referred to
as melanogenesis) by melanocytes in skin
and hair.
• Acting in the hypothalamus, α-
MSH suppresses appetite. α-MSH secreted
in the hypothalamus also contributes to
sexual arousal.

69. MSH FUNCTION
• Melanocyte-Stimulating hormone (MSH)
characterizes a group of hormones made by
the pituitary gland, hypothalamus, and skin
cells.
• MSH is essential for preserving the skin
from ultraviolet rays, the development of
pigmentation, and controlling appetite.

70. Pars Intermedia
• MSH
– Pro-opiomelanocortin Family
– Alpha
– Beta
• Also in Hypothalamus
– Involved in regulating metabolism and appetite

71. Pituitary hormones

72. Anterior Pituitary

74. Pituitary releasing hormones
• Small peptides
• Active at relative high
concentrations
• Rapidly degraded
• Low concentration in
peripheral circulation
• Special circulation allows
high concentrations to reach
targets

75. Growth hormone:
•Secretion is regulated by the action of growth hormone releasing
hormone(GHRH) released by hypothalamus.
•Sermorelin, a synthetic analogue of GHRH
•Used as diagnostic agent for testing the pituitary GH secretion in
suspected cases of childhood short stature.
•Side effect: Flushing, injection site pain, dizziness, hyperactivity and
urticaria.

76. Anterior pituitary hormones
Adrenal
Cortex
Corticosteroids
Thyroid
Thyroxine
Testosterone
Estrogen
Progesterone
ovary
Bone Growth
Muscle Mass
Fat mobilization
Milk
Production
Anterior
Pituitary Posterior
Pituitary

77. Pharmacologic applications:
• Replacement therapy
• Antagonists for excess
production of pituitary
hormones.
• Diagnostic tools for endocrine
abnormalities.

78. Anterior Pituitary
Is also called theAdenohypophysis
Secretes tropic hormones in a pulsatile fashion
Synthesizes various hormones in various specific cell
populations

79. The anterior pituitary is
actually a glandular
structure, composed of
diverse cell types that
synthesize specific hormones
to control specific peripheral
glands or tissues:
►luteinizing hormone (LH)
and follicle stimulating
hormone (FSH) that regulate
ovarian function;
►thyroid stimulating hormone
(TSH) to regulate thyroid
function;
►adrenocorticotrophic
hormone (ACTH) to regulate
adrenal cortex function;
►growth hormone (GH) for
bone and muscle;
►prolactin to stimulate milk
production in the breast. :

81. Anterior Pituitary Hormones
Each of anterior pituitary hormone is synthesized
by a cell population.
Corticotropes
Lactotropes
Somatotropes
Thyrotropes
Gonadotropes
- ACTH
- Prolactin
- GH
- Thyrotropin
- FSH, LH

82. Anterior Pituitary Hormones
Growth Hormone (GH, Somatotropin): primary
hormone responsible for regulating body growth, and is
important in metabolism
Thyroid-stimulating Hormone (TSH): stimulates
secretion of thyroid hormone & growth of thyroid gland
Adrenocorticotropic Hormone (ACTH): stimulates
cortisol secretion by the adrenal cortex & promotes
growth of adrenal cortex

83. Anterior Pituitary Hormones
Follicle-stimulating Hormone (FSH): Females:
stimulates growth & development of ovarian follicles,
promotes secretion of estrogen by ovaries.
Males: required for sperm production
Luteinizing Hormone (LH): Females: responsible for
ovulation, formation of corpus luteum in the ovary, and
regulation of ovarian secretion of female sex hormones.
Males: stimulates cell in the testes to secrete testosterone
Prolactin: Females: stimulates breast development and
milk production. Males: involved in testicular function

84. Posterior Pituitary
Comprised of the endings of axons from cell bodies in
the hypothalamus (supraoptic and paraventricular)
Axons pass from the hypothalamus to the posterior
pituitary via the hypothalamohypophysial tract
Posterior pituitary hormones are synthesized in the
cell bodies of neurons in the supraoptic and
paraventricular nuclei

85. Posterior Pituitary
Hormones synthesized in the hypothalamus are
transported down the axons to the endings in the posterior
pituitary
Hormones are stored in vesicles in the posterior pituitary
until release into the circulation
Principal Hormones: Vasopressin & Oxytocin

86. Secretion of Posterior Pituitary
Hormones
Figure 7-12: Synthesis, storage, and release of posterior pituitary hormones

87. Oxytocin
Is synthesized as the precursor hormone: prepro-
oxyphysin
Acts primarily on the mammary gland and uterus
Increases contraction of smooth muscle of the vas
deferens

88. Oxytocin
Secretion is increased during labor
May also act to facilitate sperm transport in uterus
(non-pregnancy state)

89. Posterior Pituitary: Regulation of Osmolality
Plasma osmolality is monitored by osmoreceptors in the
hypothalamus
Increases in plasma osmolality stimulates secretion of
vasopressin
Small changes above the normal plasma osmotic pressure
(285 mosm/kg) stimulate release of vasopressin

90. Vasopressin (ADH)
Is also known as antiduretic hormone (ADH)
Participates in body water regulation (Water is lost
from lungs, sweat, feces and urine on a daily basis)

91. Osmolality
• Refers to the amount of solutes in a solution
• Loss or gain of water without solutes (free water
gain or loss) changes the osmolality of ECF
• Must be regulated to maintain normal cell activity

92. Vasopressin (ADH) Secretion
Secretion is Stimulated by:
1. Large decreases in blood volume
2. Decreases in blood pressure
3. Pain, fear, trauma, and stress

93. Vasopressin Activity
Decreases water excretion by kidneys (V2 receptors)
Constricts blood vessels (V1 receptors)- arteriolar smooth
muscle
Increases adrenocorticortropin hormone (V1B receptors)
secretion from the anterior pituitary

94. • "no bad hormones – just too much or too little"
• Exogenous medication
– Replaces & exceeds normal
– Cause atrophy of gland
• Hypersecretion: too much
– Tumors or cancer
– Grave's disease- thyroxin
• Hyposecretion: too little
– Goiter – thyroxin
– Diabetes – insulin
Pathologies: Over or Under
Production

95. • Downregulation – hyperinsulinemia
• Transduction abnormalities
– Testicular feminization syndrome
– Pseudohypothyroidism
• Abnormalities of control mechanisms
Pathologies: Due to Receptors