1. Hypothalamic Hormones

2. Hypothalamus → ADH & Oxytocin → neuro- secretory axons→ Posterior pituitary
Hypothalamus → Hormones → network of capillaries (portal system)→ Anterior pituitary
ACTH, TSH, LH, FSH ( stimulatory control)
GH, PRL, MSH (stimulatory and inhibitory control)

3. General characteristics of hypothalamic hormones:
TRH, CRH, GHRH, GHIH, GnRH, Dopamine (DA)
- Small peptides and polypeptides ( exception DA) of low M.W
- Needed in very low concentrations (pg)
- Have short t1/2
- Act on receptors on plasma membrane (effects mediated through a 2nd messenger)

4. TRH (Protirelin)
Tri-peptide, synthetic analogs are available, effective orally and I.V, stimulates TSH synthesis and release, MOA via cAMP, phospholipase C to increase intracellular IP3
Mainly used:
- As a diagnostic tool (TRH test)
- To treat certain cases of hypothyroidism
Dose: 50 μg I.V, 5 mg orally, maximum response in min, DOA 2-4 hrs

5. CRH
41 a.a peptide stimulates synthesis and release of ACTH, stress ↑ CRH release
Diagnostic use
GHRH (Hexarelin, Sermorelin)
40 a.a peptide, synthetic given I.V
Diagnostic use and in the management of certain cases of dwarfism

6. GHIH (Somatostatin)
14 a.a peptide
↓ secretion of GH, ACTH, TSH, Insulin, Glucagon, Gastrin, Serotonin
Its effects on blood glucose levels are dose dependent
Low doses → hypoglycemia (↓ glucagon secretion)
High dose → hyperglycemia (↓ insulin secretion)

7. Octreotide (given S.C) & Lanreotide (given I.M)
Synthetic analogs to somatostatin with longer t1/2
mainly used in the management of:
- Acromegaly
- Carcinoid syndrome (drugs of choice)
- Insulinomas, gastrinomas
- Esophageal varices
- ?? Diabetes mellitus
Major side effects: Gall bladder stone formation and platelet abnormalities

8. GnRH (Gonadotropin Releasing Hormone; Gonadorelin) A decapeptide↓
LH; FSH
E2 ; Progesterone, follicle development
& ovulation (♀)
Testosterone; spermatogenesis (♂)

9. Pro-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly
** Structure-activity relationship
Pro-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly
** Pattern of release and MOA:
- Pulsatile (Ca++ second messenger) → ↑ LH & FSH
- Large doses or continuous administration (downregulation of pituitary GnRH receptors) → ↓ LH & FSH

10. GnRH synthetic preparations:
Leuprolide acetate, Triptorelin, Goserelin, Histrelin...
Could be given S.C, I.M, I.V
Mainly given S.C
Ineffective orally
Available in intranasal, suppositories, subdermal implants and vaginal pessaries dosage forms

11. GnRH clinical uses:
a. Pulsatile administration
- Diagnostic use
- GnRH deficiency ( Kallman’s syndrome)
Rx of ♂ & ♀ hypogonadism; induction of ovulation (infertility), delayed puberty, amenorrhea, cryptorchidism…

12. b. Continuous administration or large doses or the use of a GnRH superagonists:
- Ca prostate
- Endometriosis
- IVF
- Precocious puberty
- Uterine fibroids (uterine leiomyomas)
- ?? Contraceptive

13. Side effects to GnRH:
- Production of GnRH Abs → resistance to treatment
- Headache and abdominal pain (tolerance develops to these side effects)
- Sweating, facial flushing, hot flushes
- Osteoporosis
GnRH specific antagonist:
Ganirelix (IVF)