ANTERIOR PITUITARY

(TROPIC, ADENOHYPOPHYSEAL) HORMONES

ANTERIOR PITUITARY

Release of hormones stimulated by releasing and

inhibiting hormones from the hypothalamus
Also regulated by negative feedback
Hypothalamic hormones made by neurosecretory cells
transported by hypophyseal portal system
Anterior pituitary hormones that act on other endocrine
systems called tropic hormones

COPYRIGHT 2009, JOHN WILEY & SONS, INC.

 HORMONES OF THE ANTERIOR PITUITARY

Human growth hormone (hGH) or somatostatin

Stimulates secretion of insulin-like growth factors (IGFs) that promote
growth, protein synthesis
Thyroid-stimulating hormone (TSH) or thyrotropin
Stimulates synthesis and secretion of thyroid hormones by thyroid
Follicle-stimulating hormone (FSH)
Ovaries initiates development of oocytes, testes stimulates testosterone
production
Luteinizing hormone (LH)
Ovaries stimulates ovulation, testes stimulates testosterone production

COPYRIGHT 2009, JOHN WILEY & SONS, INC.

 HORMONES OF THE ANTERIOR PITUITARY
Prolactin (PRL)
Promotes milk secretion by mammary glands
Adrenocorticotropic hormone (ACTH) or corticotropin
Stimulates glucocorticoid secretion by adrenal cortex
Melanocyte-stimulating Hormone (MSH)
Unknown role in humans

COPYRIGHT 2009, JOHN WILEY & SONS, INC.

 NEGATIVE FEEDBACK
REGULATION

COPYRIGHT 2009, JOHN WILEY & SONS, INC.

1 1 blood
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 GROWTH HORMONE (GH)
It is a single polypeptide chain composed of 191
Structure:
amino acid residues. It has two disulfide bonds.
 Secretion:
Somatotropes of the Anterior Pituitary.
Level:
High in children.
Maximal during adolescence.
Lowest during adulthood.
Measurments:
During 24 hours.
After stimulation.
Regulation:
Stimulation: By Growth Hormone Releasing Hormone (GHRH).
Inhibition: By Somatostatin.
PHYSIOLOGICAL EFFECTS:
Direct Effects:

1- Stimulation of Lipolyses (Hydrolyses of Triglycerides).

2- Stimulation of Hepatic glucose output.
3- Production of Insulin-like growth factors (IGFs,
Somatomedins)

Indirect Effects:

Mediated by IGF-1:
1- Increase cell numbers.
2- Positive Nitrogen balance.
3- Increase Protein synthesis.
DISEASE CONDITIONS RELATED TO GH:

Deficiency:
* Dwarfism.
Excessive Secretion:
* Giantism:
Due to tumor in somatotrpes in young children or adolescents.
* Acromegaly:
Rare disease (3/Million).
Causes: 1- Benign tumor of Pituitary gland (90%).
2- Tumors of pancreas, lung or adrenal gland.
Symptoms: Enlargements of extremities.
 TREATMENT OF ACROMEGALY:

Transsphenoidal surgery to remove tumor.

Radiation therapy usually follow the surgery.

Drug Therapy:
1- Dopaminergic Agonists:
Bromocriptine (Parlodel).
2- Synthetic Somatostatin analogs:
Octeroide (Sandostatin).
 Uses of Growth Hormone:
* Replacement therapy for children with GH deficiency.
* Administered by intramuscular or subcutaneous.

Sources:
* Recombinant DNA technology.
 GROWTH HORMONE RELEASING HORMONE
(GHRH)
Structure:
Single polypeptide chain composed of 108 amino acid residues.
Function:
Stimulate the secretion of GH.
Uses:
Treatment of children with GH deficiency due to hypothalamic
defects.
Diagnoses of the cause of GH deficiency.
 THYROID GLAND

Located inferior to larynx

2 lobes connected by isthmus
Thyroid follicles produce thyroid hormones
Thyroxine or tetraiodothyronine (T4)
Triiodothyronine (T3)
Both increase BMR, stimulate protein synthesis, increase use of glucose
and fatty acids for ATP production

Parafollicular cells or C cells produce calcitonin

Lowers blood Ca2+ by inhibiting bone resorption

COPYRIGHT 2009, JOHN WILEY & SONS, INC.

THYROID GLAND

COPYRIGHT 2009, JOHN WILEY & SONS, INC.

Control of thyroid hormone secretion

Thyrotropin-releasing hormone (TRH) from

hypothalamus
Thyroid-stimulating hormone (TSH) from anterior pituitary
Situations that increase ATP demand also increase
secretion of thyroid hormones

COPYRIGHT 2009, JOHN WILEY & SONS, INC.

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effect)
Stimulate
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synthesis
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some
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catecholamines
of catecholamines
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Regulate
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 GONADOTROPIC HORMONES:
They were given this name due to their effect on Gonads.
They includes:
1- Luteinizing Hormone (LH).
2- Follicle-Stimulating Hormone (FSH).
3- Chrionic Gonadotropin (CG).

Structures:
They are glycoproteins. All glycoproteins are composed of two subunits
and . The -subunit is similar in all hormones and contain two N-
linked oligosaccharide chains. The -subunit is specific for each
hormone. In LH, TSH it contains one N-linked oligosaccharide chain,
while in CG and FSH it contain two N-linked oligosaccharide chains.
 Secretion:
LH and FSH are secreted from the Gonadotropes of the Anterior Pituitary.
CG secreted by the placenta.
Regulation:
Stimulation: Gonadotropin-Releasing Hormone from the hypothalamus (Gn
RH).
Inhibition: Feed back mechanism by sex hormones.
CG produced by placenta after fertilization.
Physiological effects:
In Males:
LH: Stimulate production of androgens by Leydig cells.
FSH: Enhance normal sperm production by Sertoli cells.
In Females:
LH: Induce Ovulation and stimulate Progesterone production.
FSH: Enhance production of Estrogen and development of follicles.
 USES:
Diagnostic uses:
Diagnosis of Pregnancy: CG in Urine or Blood.
Prediction of Ovulation: LH 36 hr before Ovulation.
Reproductive system disorder in males and females.
Therapeutic uses:
Male infertility.
Female infertility.
Cryptorchidism.
Antagonists:
Used as contraceptives.
 GONADOTROPIN-RELEASING HORMONE
(GNRH, LHRH)
Structure: Polypeptide composed of 10 amino acid residues. Secretion:
Hypothalamic neurones with onset of puberty.
Uses:
Stimulation of Gonadotropin Secretion:
Long-term pulsatile administration in cases of deficiency.
Suppresion of Gonadotropin Secretion:
Log-acting GnRH in a continuous fashion. This is required in:
Prostate cancer
Estrogen dependent breast cancers, Endometriossis.
Gonadotropin-dependent precocious puberty.
Analogs: Gonadorelin HCl (Synthetic Human GnRH).
 PROLACTIN (PRL)
Structure: It is a single polypeptide chain composed of 199 amino acid
residues. It has three disulfide bonds.
Secretion:
Lactotropes of the Anterior Pituitary.
Level:
Starts early in the fetal stages.
Decline shortly after birth and remain low in males.
In female increase with pregnancy reach maximum level at term
and remains high during lactation.
Regulation:
Inhibited by Dopamine.
No hypothalamic stimulation.
Stimulated by TRH but this is of pathological importance.
 Physiological Effects:
Breast developments and initiation of lactation.
Prolactin imbalance:
Hyperprolactinemia:
Causes:
Tumors in the lactotropes.
Dopamine antagonists.
Hypothyroidism associated with high level of TRH.
Hypothalamus or Anterior Pituitary disorders.
Renal failure.
Sympotoms:
In females: Galactorrhea, Amenorrhea, Infertility.
In males: Galactorrhea, Impotence, Infertility.
TREATMENT:
Dopamine agonists: Bromocriptine
 ADRENOCORTICOTROPIC HORMONE
(ACTH)
Structure:
Peptide hormone composed of 39 amino acid residues.
Function:
Stimulate the secretion of Corticosteroids.
Necessary for the adrenal gland otherwise atrophy of the
gland takes place.
Control:
Feed-back inhibition by corticosteroids.
Uses:
Diagnoses of Adrenal insufficiency.
 STEROIDAL HORMONES
(ADRENOCORTICOSTEROIDS, ADRENOCORTICOIDS,
CORTICOSTEROIDS, CORTICOIDS)
Secretion:
Adrenal cortex of the adrenal gland.

Regulation:
Stimulation: ACTH.
Inhibition: Feed back Mechanism.
 CLASSIFICATION OF CORTICOSTEROIDS
They are all C21 hormones.

Corticosteroids

Glucocorticoids Mineralocorticois
Regulate carbohydrates, lipids Control electrolytes and water
and proteins metabolism balance
e.g. Hydrocortisone e.g. Aldosterone.
NUMBERING SYSTEM OF STEROIDAL
RING:

21
20 23 26
22 24
18 25
12
11 17
13 27
1 19 16
9 8 14
2 10 15

5 7
HO 3
4 6
 Biosynthesis of Adrenocorticosteroids

O O

HO HO O

Cholestrol Pregnenolone Progesterone

HO
O
O
OH

O
O
21-Hydroxyprogesterone 17-Hydroxyprogesterone

HO HO
O O
HO
OH

O O

Corticosterone 11-Deoxycortisol

HO
HO O
O HO
HO CHO OH

O
O
Cortisol
Aldosterone Hydrocortisone
PHYSIOLOGICAL FUNCTIONS AND PHARMACOLOGICAL
EFFECTS:
Carbohydrates and Proteins Metabolism:
Stimulate glucose formation in the brain.
Decrease peripheral utilization of glucose.
Promote storage of glucose in the liver.
Promote gluconeogenesis.
Lipids Metabolism:
Redistribution of body fat (Buffalo hump, Moon face).
Enhance lipolyses of Triglycerides.
Electrolyte and Water balance:
Enhance reabsorption of sodium and water into plasma.
Increase urinary excretion of potassium.
 Blood Picture:
Increase hemoglobin and Red blood cells.
Decrease white blood cells.

Anti-inflammatory effects:
Suppress inflammations regardless to their cause.

Immunosuppressive Effects:
Decrease immunity as a result of decrease the WBCs.

Cell Growth:
Retardation of cell division and cell growth.
 DISEASE STATES:
Addisons disease:

Rare syndrome 1/100,000 due to Hypoadrenalism.

Causes:
Atrophy of adrenal gland.
Tuberculoses.
Low level of ACTH.
Symptoms:
Weakness, fatigue, apathy, depression and irritability.
Anemia and low blood pressure.
Loss of sodium and dehydration.
Hypersensitivity to Insulin, Hyper pigmentation.
Nausea and vomiting.
 Cushings disease:
Rare syndrome 2- 5/Million due to Hyperadrenalism.
Causes:
Tumor of the Adrenal Cortex.
Tumor of the Pituitary gland.
Symptoms:
Alteration of fat distribution.
Hypertension.
Osteoporosis.
Growth retardation.
Decrease Immunity.
Conns syndrom:
Causes:
Inability of adrenal cortex to carry out 17-hydroxylation of pregnenolone. That
leads to low level of Cortisol and high level of Aldosterone.
Symptoms:
Hypertension, Alkalosis, Polyuria, Edema.
PHARMACOKINETICS:
Absorption:
Well absorbed from all sites of administration.

Plasma Protein binding:

90% to albumin or globulin.

Half life (t1/2):

1- 1.5 hr.

Metabolism and Excretion:

Excreted in urine after glycosylation with glucuronic acid.
 Structure-Activity Relationship
Halogen & halomethylene greatly increase Topical antiinflammatory activity
Essential for activity

-F increase all activities if no OH at C-17

-F with 16dihydroxy--inactive compounds
HO 21
Ether & esters increase
O antiinflammatory &
glucocorticoid activities
Essential for antiinflammatory activity 18
& carbohydrate regulatory activity HO
12 OH
17
11 13 Essential for antiinflammatory activity
1, 2 Double bond improve carbohydrate
metabolism to Na+ retention
C D 16 CH3 or OH eleminate
19
Na+ retention activity
9 14
1
-CH3 increase
glucocorticoid activity 2 10
A B
5
3 9-Fluoro increase all activities
6 F Br Cl
O
4

Essential for activity -CH3 in Cortisol increase all activities

-CH3 in Prednisolone increase antiinflammatory activity
+
&Decrease Na retaining activity
THE HIERARCHICAL STRUCTURE OF ANT. PITUITARY
AXES MAKES MULTIPLE FEEDBACK LOOPS POSSIBLE
Not all of these loops are operative in any
hypothalamus given system.

Releasing factor

Ant. pituitary

Tropic hormone

Target gland

Final hormone(s)

Target - effects
THE CONTROL OF CORTISOL SECRETION IS AN
EXAMPLE

hypothalamus

CRF

corticotrophs

ACTH

Adrenal cortex

cortisol
 THE STRESS RESPONSE

Eustress in helpful stress / Distress is harmful

Bodys homeostatic mechanisms attempt to counteract stress
Stressful conditions can result in stress response or general
adaptation syndrome (GAS)
3 stages initial flight-or-fight, slower resistance reaction, eventually
exhaustion
Prolonged exposure to cortisol can result in wasting of muscles,
suppression of immune system, ulceration of GI tract, and failure of
pancreatic beta cells

COPYRIGHT 2009, JOHN WILEY & SONS, INC.

STRESS
RESPONSE

COPYRIGHT 2009, JOHN WILEY & SONS, INC.