Estrogen and Anti estrogen and their drugs
Introduction:
Estrogens are the female sex hormones. These hormones induces secondary sex characters and development of sex organs in female.
Natural estrogen is the estradiol which secreted by the ovary. It is synthesized in the graafian follicles, corpus luteum and placenta of the female. In male it secreted in very minut quantity.
Estradiol is rapidly oxidised to form estrone that further hydroxylated to form estriol (These two form estriol and estrone are weak potent than estradiol).
Synthetic estrogens are prefer over natural estrogens because of avoiding first pass metabolism and provide optimal therapeutic effects.
Regulation of secretion:
Daily secretion of estrogens in menstruating women varies from 10-100microgram depends on phase cycle.
Estrogens secretion start from graafian follicles by the influence of FSH. During the follicular phase, FSH level rises and reaches to ovulation phase. After ovulation corpus luteum secretes estrogen two days before menstruation.
It act as feedback inhibitor and directly or indirectly acting on pituitary as well as on hypothalamus to inhibit the release of FSH from pituitary.
Pharmacological action:
1. Secondary sex characters and sex organs:
These changes occur in female at puberty-
> growth of genitals - breasts, uterus, fallopian tube and vagina. Vaginal epithelium (endometrium) get proliferated, thickened and stratified during phase cycle.
> growth of hairs - pubic, axillary.
> behavioural changes like voice light and softened and increase Physical vigour.
> other changes acne and fominine
2. Metabolic effects:
> Estrogen is important in maintaining bone mass by retarding bone resorption. It promotes positive calcium by inducing renal hydroxylase enzyme which generates the active form of Vit D3.
> Increase cholesterol secretion and reducing bile salt secretion.
> Estrogens are weak anabolic combining with small amount of androgen may be contributing pubertal growth.
Mechanism of action:
1. Estrogen binds with cytoplasmic estrogen receptor.
2. Removal of corepressor and attachment of coactivator.
3. Initiates, combining of estrogen response element.
4. DNA transcription enhanced, mRNA formed and translocation into the cytoplasmic and start production of protein synthesis.
5. Response generation occur.
Two distinct ERs designated ER- alpha and ER- beta have been identified, cloned and structurally characterized. Most tissues express both sub-types, but ER- alpha predominates in uterus, vagina, breast, bone, hypothalamus and blood vessels, while ER- beta predominates in prostate gland of males and ovaries in females.
Uses:
1. Hormone replacement therapy:
Ovarian function impairment cause vasomotor disturbance, urogenital atrophy, osteoporosis, dermatological changes, psychological disturbance and high risk of cardiovascular disease.
> Vascular disturbance- pain, hot flushes, sweating.
> Urogenital atrophy- change vaginal pH, itching, UTI, vaginal dryness.
> Osteoporosis- loss of calcium cause thinning and weakening of bones especially of femur, radius, hip and vertebrae.
> Psychological disturbance- depressed mood, loss of libido and self confidence, anxiety and dementia.
> High risk of cardiovascular disease- coronary artery disease, myocardial infarction.
In this condition prefer, hormone replacement therapy.
2. Delayed puberty:
In female, due to ovarian function impairment cause delayed puberty in girls, treated with medication.
Side effects:
> Gynaecomastia
> Suppression of libido
> Reduction of adult stature when given to children
> Increase risk of Gallstones
> Migraine and epilepsy
> Breast cancer
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