STEROID HORMONES –

PHYSIOLOGY & PHARMACOLOGY

 Testes - Testosterone

 Ovary - Estradiol & Progesterone

 Adrenal - Glucocorticoids &

Mineralocorticoids
 STEROID HORMONES – BIOSYNTHESIS
Cholesterol
p450

Pregnenolone

Glucocorticoids Mineralocorticoids Sex Steroids

● Cortisol ● Aldosterone ● Estradiol
● Corticosterone ● Deoxycorticosterone ● Progesterone
● Testosterone
 FOLLICULAR PHASE LUTEAL PHASE
Pregnenolone Pregnenolone

17α-Hydroxypregnenolone Progesterone

Dehydroepiandrosterone 17α-Hydroxyprogesterone
OH
H3 C
18
H3 C O
H3 C
19 12 17
H3 C 11 13 16
14 15
2
1
10
9
8
O
3 5
O 4 6 7
Testostersone
Androstenedione

OH O O OH
H3 C H3 C H3 C H3 C
OH OH
C D

A B
HO HO HO HO

Estriol 17ß-Estradiol
16α-Hdroxyestrone Estrone

2-Hydroxyestrone 2-Hydroxyestradiol
and other metabolites and other metabolites
 NUCLEUS
CYTOSOLIC
RECEPTOR

DNA
TRANSCORTIN
mRNA

STEROID
NEW PROTEIN

RIBOSOMES

Schematic model of the mechanism of action of glucocorticoids

 SEX HORMONES –
INTERMEDIATES
 17 – hydroxy – pregnenolone - Follicular

 17 – hydroxy – progestrone - Luteal

 Androstenedione
ESTROGENS/PROGESTERONE –
FUNCTIONS

 Secondary Sex Characteristics

 Ovulatory/ Menstrual Cycle

 Pregnancy

 Metabolism
Steroidal,
Natural

OH O
H3 C H3 C

HO HO

Estradiol Estrone

OH
H3 C
OH

HO

Estriol
 ESTROGENS - SOURCE
 Premenopausal - Ovary

 Postmenopausal - Dehydroepiandro
sterone (DHA)

 Pregnancy - Androstenedion
↑
Fetoplacental Unit
 17-ß-Estradiol H3 C
OH

HO

Reduction Hydroxylation

Oxidation
O OH
H3 C H3 C
OH

Hydroxylation Reduction HO
HO

Estrone Estriol

Natural estrogens and their metabolic interconversions

ESTROGENS – GENITAL EFFECTS

 Growth- Uterus, Vagina, Fallopian Tubes

 ↑ Size and Number- Endometrium Cells

 Amount and Elasticity- Cervical mucus

 Breast Enlargement
ESTROGENS – METABOLIC ACTION
 Accelerate Growth at Puberty

 Stimualte Closure of Epiphysis

 Maintain Bone Mass

  Prolactin Secretion
  Antithrombin III & LDL
  SBG, TBG, VII, X, HDL
 ESTROGENS – CLINICAL USES
 Menopausal Symptoms
 Senile Atrophic Vaginitis
 Dysmenorhea
 Postmenopausal Osteoporosis
 Prostate Carcinoma
 Hirsutism
 Contraception
 ESTROGENS – SYNTHETIC
ANALOGS
 Ethinyl Estradiol (Estinyl)

 Quinestrol (Estrovis)

 Conjugated Estrogens (Premarin)

 Diethylstillbestrol (Stilphostrol)
 ESTROGENS – SIDE EFFECTS
 Endometerial Hyperplasia + Bleeding

 Breast Engorgement
 Thromboembolic Events
 Carbohydrate Intolerance
 Na+ , H2O Retention
 Cholestatic Jaundice
 DRUG INTERACTION

 Warfarin
 Phenytoin
 Carbamazepine
 Rifampin

 Phenylbutazone
 ANTIESTROGENS

 Tamoxifen – Nolvadex

 Clomiphene – Clomid

 Raloxifene
 PROGESTINS – BIOLOGICAL ACTIONS

 Enhances estrogen-primed endometrial activity

 Suppresses gonadotropin secretion

 Promotes breast development and lactation

 Elevates body temperature

 Decreases fallopian tube contraction

PROGESTERONE – CLINICAL USES
 Contraception
 Dysfunctional Uterine Bleeding
 Dysmenorrhea
 Endometriosis
 Postpone Mensturation
 Postpartum Suppression of Lactation
PROGESTERONE – SIDE EFFECTS

 Edema

 Epiphysis Closure

 Glucose Intolerance

 TBG, Clotting Factors (VII, VIII, IX, X)

 ESTROGENS, PROGESTERONE –
CONTRAINDICATION
 Thromboembolic Disease

 Impaired Liver Function

 Breast Carcinoma

 Migraine Headache
 ANTIPROGESTINE

 Ru 486 - Mifepristone
 ORAL CONTRCEPTIVES

 Combination Pills

 Progestin Pills

 Progestin Implants

 Postcoital Contraception
 ORAL CONTRACEPTIVES –
SIDE EFFECTS
 Glucose Intolerance

 Hypertension and MI

 Thromboembolic Disorders

 Vaginal and Uterus Carcinoma

 LDL ( Progesterone)
HDL
 ESTROGENS –
ORAL CONTRACEPTIVES

 Ethinylestradiol
 Mestranol
PROGESTINS–
ORAL CONTRACEPTIVES
 Norgestrol
 Norethindrone
 PROGESTERONE –
SYNTHETIC ANALOGS

 Medroxyprogesterone (Provera)

 Northindrone (Aygestin)

 Megestrol (Megace)

 Noregestimate

 Desogestrel
POSTCOITAL CONTRACEPTIVES

 Conjugated Estrogen

 Ethinyl Estradiol

 Diethylstillbestrol

 Norgestrol

 Mifepriston (Ru 486)

 UTERINE DRUGS
A. Induction of Labor
● Oxytocin
● PGE2 (Dinoprostone)
B. Induction of Abortion
● Mifepristone
● PGE1 (Gemeprost)
C. Uterine Relaxants
● ß2 - Adrenoreceptor
 Salbutamol
● Magnesium Sulfate