Download Pituitary Hormones

Pituitary Hormones
Anterior Pituitary Hormones
ACTH
Simple peptides
MSH
GH
Proteins
PRL
LH
Glycoproteins
FSH
TSH

Posterior Pituitary Hormones
Simple peptides (9 a.a)
ADH (Vasopressin)
Oxytocin
 Hypothalamic hormones regulating the anterior
pituitary hormones reach the anterior pituitary
through a network of capillaries (portal system)
whereas ADH and oxytocin reach the posterior
pituitary via neurosecretory axons

Anterior Pituitary Hormones
Hypothalamic lesion or removal → ↓ Ant. Pit H’s
except PRL
Hypothalamic stimulation → ↑ Ant. Pit H’s except
PRL
 TSH
↑ T3 & T4 through ↑ cAMP, ↑ Iodine uptake
↑ iodination and hydrolysis of thyroglobulin
** diagnostic use
ACTH
Derived from larger precursor (Pro-opiocortin)
↑ cortisol release
Undergoes circadian rhythm
Acthar and Cosyntropin=Tetacosactrin (Cortrosyn®)
are synthetic analogs
Uses:
- Diagnostic use (given I.V or I.M)
- Certain cases of adrenal insufficiency

Growth hormone (Somatropin)
- Species specific
- MOA Unclear, its effects believed to be mediated
through IGFs (Somatomedins) which are formed
in the liver , kidneys, muscles and other tissues
- GH stimulates growth of soft tissues and bones
- ↑ lipolysis
- ↑ gluconeogenesis & ↓ glucose utilization
(diabetogenic effect)
- PRL-like activity

Factors ↑ GH release:
- Sleep, Arginin, Insulin, Hypoglycemia
- β-adrenergic antagonists, Clonidine, Bromocriptine
and Levodopa in normal individuals
 Factors ↓ GH release:
- Bromocriptine in acromegalics
- Somatostatin synthetic analogs

Disorders affecting GH secreting cells:
Hypersecretion → Gigantism, Acromegaly
Rx
- Surgery;
- Somatostatin synthetic analogs;
- DA agonists (Bromocriptine; Cabergoline) and
- Pegvisomant (GH-receptor antagonist, given SC,
major side effects include abnormal liver enzymes
and some reports indicated increased growth of
GH-secreting pituitary tumors)

Hyposecretion of GH → Dwarfism
Rx
- GH-replacement therapy with S.C or I.M recombinant
human GH preparations:
Somatropin (Humatrope®)
Somatrem (Protropin®)
- Mecasermin (recombinant human IGF-1); mecasermin
rinfabate (recombinant human IGF-1 +IGF binding
protein-3=IGFBP-3), given SC in dwarf with IGF-1
deficiency not responding to GH, hypoglycemia is a major
side effect (less with mecasermin rinfabate)
Side effects of synthetic rHGH products:
- Water retention
- The development of antibodies to HGH
- Insulin resistance and diabetes
- Hypertension
- Less frequent side effects include carpal tunnel
syndrome, abnormal bone growth, reduced life
span, disturbed insulin metabolism, leukemia,
overgrowth of connective tissue, and tumors, ↑
intracranial pressure with papilledema

Prolactin (PRL)
Ant. Pit; Placenta
** Dopamine (DA)
** Has GH-like activity
Role in ♂s ??? ↑ PRL (↓ LH & FSH) → ♂ impotency
& infertility
In ♀s:
- Breast development (puberty; pregnancy)
- Lactation
- ↓ LH & FSH (galactorrhea amenorrhea syndrome)

Factors/drugs ↑ PRL:
- Pregnancy, sleep, nursing, stress (surgery, exercise)
- TRH, Estradiol, DA antagonists (antipsychotics=
Phenothiazines, Haloperidol, Metoclopramide..)
- Methyldopa, Reserpine, Diazepam, Opiates,
Meclizine, Imipramine…
 Factors/drugs ↓ PRL:
DA agonists (Bromocriptine, Pergolide, Levodopa)
Apomorphine, Clonidine , MAO inhibitors
(Pargyline)

Clinical uses to bromocriptine:
- Hyperprolactinemia in ♂s and ♀s irrespective of its
causes
- Suppression of lactation
- Acromegaly
- Parkinson’s disease
Bromocriptine is given orally

Gonadotropins: LH & FSH
Glycoproteins
LH
α
β
FSH
TSH
hCG
α DNA
β DNA
α mRNA
β mRNA
α protein
β protein
α glycoprotein
β glycoprotein
Complete hormone
Storage
Release
-
GnRH
↓
LH; FSH
↓
E2 ; Progesterone, follicle development
& ovulation (♀’s)
Testosterone; spermatogenesis (♂’s)
MOA of LH & FSH:
- Surface receptors; cAMP 2nd messenger
- LH stimulates desmolase enzyme → ↑
steroidogenesis in gonads
- LH helps in the descent of testes during fetal life
 Source of LH & FSH:
Natural human source. Human menopausal
gonadotropins (HMG; Menotropin) (Mainly FSH)

hCG
Produced by the placenta
Has similar pharmacological properties to LH
Obtained from the urine of pregnant ladies
 Clinical uses to gonadotropins:
- Infertility in ♂’s and ♀’s due to LH & FSH
deficiency
- I.V.F
- Cryptorchidism (hCG; I.M)

Side effects to gonadotropins:
- Allergy
- Ovarian hyperstimulation syndrome
- Multiple births
- Production of specific antibodies
- Precocious puberty and gynecomastia

*** If the problem is sexual function
Give estrogen or testosterone
*** If the problem is infertility:
- GnRH in pulses
- LH, FSH, hCG
- Estrogen (♀’s); testosterone (♂’s)
- Bromocriptine
- Clomiphene citrate or Tamoxifen (estrogen
antagonists) in ♀’s & ♂’s

MOA of estrogen antagonists as antiinfertility agents :
X
GnRH
X
↓
E2
LH; FSH
↓
E2 ; Progesterone (♀)
Testosterone (♂)
Posterior Pituitary Hormones
ADH & Oxytocin
Nonapeptides (9 a.a)
Known as neurohormones
Synthesized in the hypothalamus
Stored in the posterior pituitary → release
? Role as neurotransmitters (V1R’s in CNS)
Role of oxytocin in man is unknown

ADH ( Vasopressin)
Physiological and pharmacological actions:
- Vasoconstriction (V1 receptors)
- ↑ reabsorption of H2O from collecting ducts (V2
receptors)
- ↑ synthesis of certain clotting factors (VIII, Von
Willebrand) (V2 receptors)
- ↑ ACTH release (V3 receptors)
- Oxytocin-like activity

Factors/Drugs ↑ ADH release:
- Hypovolemia, hyperosmolarity, pain, stress,
nausea, fever, hypoxia
- Angiotensin II
- Certain prostaglandins
- Nicotine, cholinergic agonists, β-adrenergics
- Tricyclic antidepressants
- Insulin, morphine, vincristine…

Factors/Drugs ↓ ADH release:
- Hypervolemia
- Hypoosmlarity
- Alcohol
- Atrial natriuretic peptide
- Phenytoin
- Cortisol
- Anticholinergics, α-adrenergics, GABA...

Disorders affecting ADH release:
A. Excess production (inappropriate ADH secretion) →
Dilutional hyponatremia
Causes:
- Head trauma, encephalitis
- Meningitis, oat cell carcinoma
Rx:
- Water restriction (Rx of choice)
- Hypertonic saline solution
- Fludrocortisone → ↑ Na+ blood level
- ? ADH antagonists

ADH antagonists
- Conivaptan, V1 & V2 R antagonist given IV
- Tolvaptan; Lixivaptan & Satavaptan, orally
effective selective V2R antagonists
Clinical uses:
- Inappropriate ADH secretion
- CHF

B. Deficiency of ADH → Diabetes insipidus (DI)→
polyurea
Causes:
- Idiopathic DI
- Congenital
- Hypothalamic surgery, head trauma, malignancies
- Familial DI, overproduction or decreased clearance
of vasopressinase (gestational DI)
Rx:
ADH preparations (HRT)
ADH preparations:
- Natural human (Pitressin)
Given I.M, S.C, has short half-life (15 min)
- Lypressin ( synthetic, porcine source)
Given intranasally, I.V, I.M, has short DOA (4hrs)
- Desmopressin (synthetic ADH-like drug)
Given intranasally, S.C
Most widely used preparation, has long DOA (12 hrs)

- Felypressin (synthetic ADH-like drug)
Has strong vasoconstrictor activity
Mainly used in dentistry
 Clinical uses to ADH:
- DI
- Nocturnal enuresis
- Hemophilia
- Bleeding esophageal varices
Side effects to ADH preparations:
- Allergy
- Pallor
- Headache, nausea, abdominal pain in ♀’s
(oxytocin-like activity)
- Anginal pain (coronary artery vasospasm)
- H2O intoxication (massive doses)
- Gangrene (rare particularly with desmopressin= has
great affinity to V2 receptors)

Oxytocin (9 a.a peptide)
- Contracts the myoepithelial cells of the breast →
milk letdown; milk ejection
Major stimuli, baby cry, suckling
- Contracts the uterus → delivery
The uterus is insensitive to oxytocin in early
pregnancy but its sensitivity increases with
advanced pregnancy reaching maximum at time of
delivery
- Has slight ADH-like activity
- Role in man ???

Oxytocin MOA:
- Surface receptors → stimulation of voltage-sensitive
Ca++ channels → depolarization of uterine muscles
→ contractions
- ↑ intracellular Ca++
- ↑ prostaglandin release

Clinical uses to oxytocin:
- Induction of labor
Drug of choice given in units in an I.V infusion
- Postpartum hemorrhage, I.M. Ergot alkaloids are
better (ergonovine, methylergonovine, syntometrine=
oxytocin+ ergometrine)
- Breast engorgement, intranasally
- Abortifacient, I.V infusion. ≥ 20 weeks of gestation,
ineffective in early pregnancy

Side effects to oxytocin:
- Rupture of the uterus
Major and most serious side effect
- H2O intoxication and hypertension
Due to its ADH-like activity
 Specific oxytocin antagonist:
Atosiban (inhibitor to uterine contraction=tocolytic),
effective in the management of premature delivery,
given IV
