A- Posterior Pituitary Hormones G3FR_79

Vasopressin = Antidiuretic Hormone “ADH” Oxytocin

• Vasopressin is synthesized in neuronal cells in the hypothalamus and released from nerve terminals in the posterior pituitary. • Oxytocin is a non-peptide that is synthesized in cell
• Vasopressin acts through V1 & V2 receptors. bodies in the hypothalamus and transported through
V1 receptors V2 receptors the axons of these cells to posterior pituitary ·
MOA • Gq-coupled receptors • Gs-coupled receptors
• cause V.C. • Renal: !insertion of water channels in the luminal membranes of CD in kidney "!water reabsorption.
• Extra-renal: regulate the release of coagulation factor VIII and von Willebrand factor.
Desmopressin
USES Used to stop bleeding from • Selective V2 agonist. It is administered orally, nasally, or parenterally in: • Used to induce labor "
esophageal varices. 1- Pituitary diabetes insipidus. 2- mild hemophilia 3- von Willebrand disease causes effective uterine contraction
Vasopressin Antagonists Oxytocin receptor antagonist
1- Conivaptan & tolvaptan 2- Demeclocycline 3- Lithium Atosiban
MOA Vasopressin receptors antagonist. Tetracycline antibiotic with Antagonistic to vasopressin Oxytocin receptor antagonist
vasopressin antagonistic effect.
USES Dilutional hyponatremia & water retention associated with SIADH. SIADH. Too toxic to be used in SIADH. Tocolytic to prevent preterm labor.

B- Hypothalamic & Anterior Pituitary Hormones

Hypothalamic Hormone Anterior pituitary hormones Target organ Target Organ mediator
“Growth hormone-releasing hormone” GHRH” (+) “Growth hormone” GH (somatotropin) Liver, muscle, bone, kidney, and others Insulin-like growth factor-1(IGF-1)
“Somatostatin” "SST"(-)
“Thyrotropin-releasing. Hormone” TRH (+) “Thyroid-stimulating hormone” TSH Thyroid T3 &T4
“Corticotropin-releasing hormone” CRH (+) “Adrenocorticotropic hormone” ACTH Adrenal cortex Glucocorticoids, mineralocorticoids, androgens
“Gonadotropin-releasing hormone” GnRH (+) “Follicle-stimulating hormone” FSH Gonads Estrogen, progesterone, testosterone
“Luteinizing hormone” LH
Dopamine (-) Prolactin (PRL) Breast
1- Growth Hormone (GH)
Growth hormone is required for normal growth during childhood and adolescence. Moreover, it is an important regulator of lipid and carbohydrate metabolism through life
Its effects are mediated through the production of insulin like growth factor 1 (IGF-1) and 2 (IGF-2) in peripheral tissues.
Growth Hormone Growth Hormone Antagonists
1- Somatropin 2- Mecasermin 1. Somatostatin Analogs 2. Pegvisomant 3. Dopamine D2 Receptor Agonists
Octreotide & lanreotide Bromocriptine
Source • A recombinant form of human GH. • Complex of recombinant human • long-acting synthetic analogs of • long-acting mutant form of GH
IGF-1 and its binding protein. somatostatin.
MOA • Inhibits release of GH, glucagon, • GH binding to its receptors causes dimerization of 2 • They are more effective at inhibiting prolactin
insulin, and gastrin. receptors that initiates cellular signaling. release than inhibiting GH release
• Pegvisomant " bind GH receptors but without
conformational changes required for receptor activation
" inhibit GH effects on its receptors
Uses • GH deficiency in children and adults. • Cases not respond to GH therapy • Acromegaly • GH receptor antagonist Approved for acromegaly • High doses of D2 receptor agonists have some
• Children with genetic diseases associated • Administered parenterally to • Carcinoid, gastrinoma, efficacy in ttt of small GH-secreting tumors
with short stature “turner’s syndrome” children with IGF-1 deficiency. • Other endocrine tumors.
SE • May cause hypoglycemia. • GIT disturbances, gallstones,
• Cardiac conduction abnormalities
 2- Follicle-Stimulating Hormone FSH & Luteinizing Hormone LH G3FR_80
Action Uses of Gonadotropins & their analogs Ovulation induction protocols that use gonadotropins
In women have 3 basic steps:
- FSH " stimulates follicle development • Induce ovulation in women with anovulation. 1. Endogenous gonadotropin production inhibited by GnRH agonist or antagonist.
- both FSH & LH " regulate ovarian steroidogenesis 2. Follicle development is driven by daily injections of a preparation with FSH
In men activity (menotropins).
- FSH " regulates of spermatogenesis, • Stimulate spermatogenesis in infertile men. 3. Oocyte maturation induced by injection of LH or LH analog human chorionic
- LH " stimulates testicular androgen production gonadotropin (hCG).
Gonadotropin preparations (all are administered parenterally)
1. Menotropins 2. FSH and its analogs 3. LH and its analogs
A mixture of FSH and LH. Urofollitropin Follitropin alpha & beta Human chorionic gonadotropin (hCG) Lutropin
• They are purified from the urine Purified preparation Recombinant forms of human FSH. • Produced by placenta to support corpus luteum during early stages of pregnancy. Recombinant
of postmenopausal women extracted from urine of • Has similar structure to LH & produces its effects through activation of LH receptors. form of human
postmenopausal women • hCG is either purified from human urine or produced by recombinant techniques. LH
Gonadotropin-Releasing Hormone (GnRH) and Its Analogs Gonadotropin-Releasing Hormone (GnRH) Antagonists
• Leuprolide, Goserelin & Nafarelin are long-acting GnRH agonist Ganirelix
• Pulsatile administration of GnRH stimulates gonadotropin release by anterior pituitary gland.
• Continuous administration of GnRH or its analogs inhibits gonadotropin release.
Uses
Continuous GnRH agonist treatment is used to suppress endogenous gonadotropin secretion in: • Can be used during ovulation induction instead of GnRH agonists to suppress endogenous
1. Women undergoing ovulation induction with gonadotropins. gonadotropin production.
2. Endometriosis • Newer GnRH antagonists were approved for advanced prostate cancer.
3. Children with precocious puberty.
4. Advanced prostate cancer.
Adverse effects of continuous GnRH agonist application Advantages over continuous GnRH application
1. Women: typical symptoms of menopause (hot flushes, sweats & headache). 1. They do not cause initial tumor flare-up when used for advanced prostate cancer.
2. Men: hot flushes, gynecomastia, decreased libido, and anemia. 2. They are less likely to cause the ovarian hyperstimulation syndrome when used for ovulation
3. Cases with prostate cancer & precocious puberty: first few weeks of therapy can temporarily induction
exacerbate condition.
4. Long-use: osteoporosis.

3- Prolactin Antagonists (Dopamine D2 Receptor Agonists)

Bromocriptine & pergolide
• Prolactin regulates lactation. In women and men, • Prolactin-secreting adenomas " Hyperprolactinemia " infertility and galactorrhea
• Dopamine is the physiologic inhibitor of prolactin release. “Prolactin secreting adenomas are usually sensitive to dopamine suppression”.
• D2 receptor agonists "#serum prolactin & restoring fertility in cases of hyperprolactinemia.
• High doses of dopamine agonists can also be used in treatment of acromegaly.
 Gonadal Hormones & Inhibitors G3FR_81
Ovarian hormones Androgens
Ovary is the primary source of gonadal hormones in women. Under control of FSH & LH, each menstrual cycle consists of: • Testosterone the main androgen, produced in testes & adrenal cortex.
l. A follicle in the ovary develops and secretes estrogen. • synthesized from progesterone and dehydroepiandrosterone (DHEA).
2. When the ovum is released, the follicle is transformed into corpus luteum which secretes progesterone. • In several organs (e.g. prostate), it is converted to dehydroepiandrosterone (DHT),
3. If the ovum is not fertilized, the corpus luteum degenerates and the endometrium is shed. • Testosterone is not administered orally (has extensive hepatic metabolism).
• It may be given by injection (long-acting esters) or by transdermal patch.
Estrogens Progestins Testosterone
Effects • Growth of the genital structures during childhood. • Progesterone is natural progestin produced by ovary • Necessary for normal development of the male fetus and infant.
Or • Secondary sexual characteristics and the growth spurt with puberty • Progesterone induces secretory changes in endometrium & • Responsible for the development and maintenance of sex pattern in males
action • Metabolic effects: - #bone resorption. -!enhances coagulation maintain pregnancy (e.g. growth of facial, pubic, and axillary hair).
- !plasma triglycerides -!HDL-cholesterol -#LDL-cholesterol • Other progestins can stabilize the endometrium but cannot • Has anabolic effect (increases muscle mass and increases red blood cell
• Continuous administration of estrogen, especially if combined with support pregnancy production)
a progestin "#secretion of gonadotropins from anterior pituitary. • High doses suppress gonadotropin & often cause anovulation • Testosterone also helps maintain normal bone density
MOA Bind to intracellular receptors, and then the complex enters the nucleus, where it modulates gene expression
Clinical 1. hypogonadism in young females. 1. Hormonal contraceptives (either alone or combined with 1. Replacement therapy in hypogonadism.
uses 2. Hormone replacement therapy (HRT) in women with estrogen estrogen). 2. To enhance weight gain in wasting syndromes (e.g. AIDS patients).
deficiency "#hot flushes & atrophic changes in urogenital tract & 2. They are combined with estrogens in HRT to prevent
prevents osteoporosis. a. Premature ovarian failure. b. Menopause. estrogen -induced endometrial cancer. N.B. Anabolic steroids have been used illegally by athletes to increase muscle bulk
c. Surgical removal of the ovaries. 3. Progesterone is used in assisted reproductive technology and strength and to enhance athletic performance.
3. Estrogens are components of hormonal contraceptives methods to promote & maintain pregnancy
Toxicity 1. Premature closure of the epiphyses " short stature (when used in Toxicity of progestins is low l. females: virilization (hirsutism, deepened voice) & menstrual irregularity.
& young girls for hypogonadism). 1. HTN & decrease HDL. 2. female fetus (if used by pregnant females): virilization of the fetus's external genitalia.
SE 2. !risk of endometrial cancer (prevented by adding a progestin) 2. Long- use "reversible decrease in bone density (due to 3. males: excessive doses can cause feminization e.g. gynecomastia, testicular atrophy and
3. Small increase m the risk of breast cancer and cardiovascular ovarian suppression & #production of estrogen) infertility (paradoxical effect) due to: - Feedback inhibition of the pituitary
events (myocardial infarction, stroke) in postmenopausal women. 3. Delayed restoration of ovulation after termination of therapy - Conversion of the exogenous androgens to estrogens.
4. Dose-dependent toxicity: nausea, breast tenderness, increased risk 4. Androgenic progestins (19-nortestosterone derevatives) e.g. 4. In both sexes, high doses of anabolic steroids can cause:
of migraine, thromboembolism (e.g. DVT), gallbladder stones, Older preparations (e.g. L-norgestrel) are more androgenic - Cholestatic jaundice. - Elevation of liver enzyme levels - !risk of HHC.
hypertriglyceridemia, and hypertension than the newer progestins (e.g. norgestimate)
Antiestrogens and Antiprogestins Antiandrogens
A- Selective Estrogen Receptor Modulators (SERMs) B- Pure Estrogen (1) Receptor inhibitors (2) 5α-reductase inhibitors
Receptor Antagonists
1. Tamoxifen 2- Raloxifene 3. Clomiphene Fulvestrant Flutamide Spironolactone Finasteride
Antagonist • It inhibits 5α-reductase, which is responsible
- Effective in hormone- • in breast tissue "#incidence of breast • # estrogen receptors in Pure Estrogen Receptor • Competitive +
• K -sparing diuretic for conversion of testosterone to DHT, which
responsive breast cancer cancer in women who are at high risk pituitary "#-VE feedback Antagonists antagonist at • Also inhibits is the active form of the hormone in some
"!FSH & LH "(+) tissues (prostate and hair follicles).
- Hot flushes. • Hot flushes & !risk of thrombosis (in all tissue) androgen receptors. androgen receptors
MOA ovulation.
& Agonist Partial agonist Uses
- On bone " prevent osteoporosis • Unlike tamoxifen, it has • Approved for Induction of pregnancy Tamoxifen-resistant breast • Decrease action of • Hirsutism in women. 1. Benign prostatic hyperplasia (BPH).
Action in postmenopausal women No estrogenic effects on prevention & ttt of cancer endogenous 2. Prevention of hair loss in men.
- At endometrial receptors " endometrial tissue osteoporosis in ✓ Because finasteride does not interfere with
androgens in prostate
endometrial hyperplasia & !risk (no!risk of endometrial postmenopausal
cancer. the action of testosterone, it is less likely to
of endometrial cancer). cancer women
- !risk of venous thrombosis - !risk of thrombosis cause impotence, infertility, and loss of libido
C- Synthesis Inhibitors D- Anti-progestins 3) GnRH analogs and antagonists: 4) Inhibitors of steroid synthesis:
1. Anastrozole 2. Danazol 3. GnRH analogs Mifepristone Ketoconazole
(continuous administration) Progesterone Antagonist Suppress gonadotropin secretion, especially LH "
Inhibits aromatase (responsible for the Inhibits cytochrome P450 enzymes Antifungal drug, inhibits gonadal and adrenal
and antagonists: reduces production of testosterone.
MOA last step in estrogen synthesis). involved in gonadal steroid synthesis steroid synthesis by inhibiting CYP450 enzymes
breast cancer. endometriosis and fibrocystic See before In combination with • GnRH analogs " prostatic carcinoma. Initially, • used in prostate cancer
disease of breast. misoprostol (PGE analog), as tumor flare can result from initial increase in Note: Combined hormonal contraceptives
testosterone synthesis caused by initial agonistic action - They can be used in hirsutism.
Uses abortifacient in early
of the GnRH analogs. This can be avoided by adding - The estrogen increases the production of sex
pregnancy flutamide in the first week of therapy. hormone-binding globulin by Liver "# free androgen
• GnRH receptor antagonists approved for advanced in the blood "#male-pattern hair growth
prostate cancer
 Hormonal contraception G3FR_82
P/K Available in multiple forms including oral pills, long-acting medications, transdermal patches, vaginal rings, and, intrauterine devices (IUDs).
• Hormonal contraceptives have two forms: Postcoital contraceptives
a. Combined preparations of an estrogen & progestin: b. Progestin-only preparations. (emergency contraception)
1. Monophasic preparations 2. Biphasic & triphasic preparations 3. Progestin-only preparations • Prevent pregnancy if administered within 72 h
Types of Estrogen and progestin in which the progestin or estrogen concentrations, after unprotected intercourse
oral concentrations are constant or both, changes during the month (to be more • Oral preparations containing a progestin (L-
CCPs throughout the menstrual closely similar to the hormonal changes during norgestrel) alone, estrogen alone, or the
cycle. menstrual cycle) combination of estrogen & progestin are effective.
• The combined preparations have several actions: • Act mainly through inhibition of • The progestin-only preparation causes fewer side
MOA 1. Inhibition of ovulation (the primary action). fertilization and implantation rather effects than the estrogen containing preparations.
2. Decreasing the possibility of fertilization and implantation by changing the than inhibition of ovulation
properties of cervical mucus, uterine tubes, and endometrium
(the incidence of dose-dependent toxicity has been reduced after the introduction of the low-dose combined oral contraceptives).
1. Thromboembolism:
Toxicity - The risk increases with combined contraceptive pills as estrogen increases blood coagulability.
& - Include myocardial infarction, stroke, deep vein thrombosis, and pulmonary embolism.
SE - The risk is higher in older women, smokers, women with a personal or family-history of thromboembolic disorders.
2. Breast cancer:
✓ No evidence that hormonal contraceptives can increase the risk of developing breast cancer, but there may be an earlier onset of it.
3. Other toxicities:
a. Breakthrough bleeding (with progestin-only preparations).
b. Nausea, breast tenderness, headache, skin pigmentation, and depression.
c. Preparations -containing older, more androgenic progestins can cause weight gain, acne, and hirsutism.