L 31.OVARIAN HORMONES

OBJECTIVES of the lecture is to discuss; OBJECTIVES of the lecture is to discuss; The ovarian hormones The ovarian hormones Physiological effects of estrogen, progesterone, relaxin, inhibin Physiological effects of estrogen, progesterone, relaxin, inhibin And the rgeulation of above hormones. And the rgeulation of above hormones.

Learning objectives At the end of this class students should be able to At the end of this class students should be able to List the ovarian hormones List the ovarian hormones Describe the mechanisms of action and physiological effects of Estrogen, Progesterone, Relaxin and Inhibin Describe the mechanisms of action and physiological effects of Estrogen, Progesterone, Relaxin and Inhibin Describe with help of flow chart the regulation of ovarian hormones. Describe with help of flow chart the regulation of ovarian hormones.

MAJOR HORMONES: Estrogen & Progesterone MAJOR HORMONES: Estrogen & Progesterone Other hormones: Other hormones: Inhibin Inhibin Activin, relaxin, other peptides Activin, relaxin, other peptides

ESTROGEN Source: Mainly coordinated enzymatic activities between the theca and granulosa cells of the ovarian follicle. theca cell– produced androgens are aromatized to estradiol by granulosa cells. Source: Mainly coordinated enzymatic activities between the theca and granulosa cells of the ovarian follicle. theca cell– produced androgens are aromatized to estradiol by granulosa cells. Partly corpus luteum, during early pregnancy corpus luteum later placenta. Partly corpus luteum, during early pregnancy corpus luteum later placenta. 17 β Estradiol (E2)- most potent 17 β Estradiol (E2)- most potent Estrone (E1)- less potent Estrone (E1)- less potent Estriol (E3)- least potent Estriol (E3)- least potent

Chemistry: C18 steroids Chemistry: C18 steroids Raw material: Cholesterol Raw material: Cholesterol Transport: Free & Bound Transport: Free & Bound 60% with Albumin, 38% with SBG 60% with Albumin, 38% with SBG Metabolism: As glucoronide & sulfate Metabolism: As glucoronide & sulfate conjugates conjugates MECH: Like other steroids MECH: Like other steroids

Mechanism of action Most of the effects of estrogens are genomic, that is, due to actions on the nucleus, but some are so rapid that it is difficult to believe they are mediated via production of mRNAs. Most of the effects of estrogens are genomic, that is, due to actions on the nucleus, but some are so rapid that it is difficult to believe they are mediated via production of mRNAs. These include effects on neuronal discharge in the brain and, possibly, feedback effects on gonadotropin secretion. These include effects on neuronal discharge in the brain and, possibly, feedback effects on gonadotropin secretion.

Actions of estrogen On female reproductive system: On female reproductive system: On the uterus On the uterus On the uterine cervix On the uterine cervix On the ovaries On the ovaries On the vagina On the vagina On the breasts On the breasts

On uterus Hyperplasia of uterine myometrium & hypertrophy of existing cells. Hyperplasia of uterine myometrium & hypertrophy of existing cells. Increases contractile proteins Increases contractile proteins Increases excitability of myometrium Increases excitability of myometrium Reconstruction of endometrium during proliferative phase Reconstruction of endometrium during proliferative phase Withdrawal causes sloughing of endometrium Withdrawal causes sloughing of endometrium

On uterine cervix Causes watery mucus secretion from uterine cervix which helps in easy transportation of sperms Causes watery mucus secretion from uterine cervix which helps in easy transportation of sperms

On the ovaries During follicular phase stimulates the maturation of ovarian follicles During follicular phase stimulates the maturation of ovarian follicles Positive feed back on LH, thereby LH surge causes ovulation Positive feed back on LH, thereby LH surge causes ovulation

On the vagina Increases epithelial and vascular growth Increases epithelial and vascular growth Cornification of superficial layers Cornification of superficial layers Deposition of glycogen in the vaginal epithelium Deposition of glycogen in the vaginal epithelium

On the breasts Increases ductal growth Increases ductal growth Fat deposition Fat deposition Areolar pigmentation Areolar pigmentation Increases vascularity Increases vascularity

OTHER ACTIONS Feminization and development of secondary sex characters Feminization and development of secondary sex characters Calcification of bones. Absence of this hormone after menopause leads to osteoporosis Calcification of bones. Absence of this hormone after menopause leads to osteoporosis At puberty initially bone growth & finally closure of epiphyseal plates, there by no further linear growth. At puberty initially bone growth & finally closure of epiphyseal plates, there by no further linear growth. Plays important role in regulation of ovarian function by negative or positive feed back at the level of Pituitary & Hypothalamus Plays important role in regulation of ovarian function by negative or positive feed back at the level of Pituitary & Hypothalamus

Stimulates Prolactin secretion during pregnancy, but inhibits prolactin’s milk producing action during pregnancy Lowers blood cholesterol Sodium & water retension Sodium & water retension Makes sebaceous gland secretions watery Prolonged action (with pharmacological dose)causes carcinogenic effect on breast & mammary glands

PROGESTERONE Naturally occuring P is a C21 Steroid Naturally occuring P is a C21 Steroid Source: Mainly corpus luteum, partly granulosa cells of graffian follicle Source: Mainly corpus luteum, partly granulosa cells of graffian follicle Transport: Only 2% is free. Transport: Only 2% is free. 80% with Albumin & 18% with corticosteroid binding globulin 80% with Albumin & 18% with corticosteroid binding globulin Metabolized to Pregnanediol & excreted as its glucoronide conjugate Metabolized to Pregnanediol & excreted as its glucoronide conjugate

Mechanism of action In the absence of hormone, receptors binds to heat shock protiens & they cover the DNA binding domain there by remain inactive In the absence of hormone, receptors binds to heat shock protiens & they cover the DNA binding domain there by remain inactive Genomic actions like other steroids: receptors are present in the cytosol of target cells. P crosses cell membrane & binds to PR. Now the heat shock protein dissociates from the PR. Now the PR +P moves to target gene. Induces mRNA & specific proteins. Genomic actions like other steroids: receptors are present in the cytosol of target cells. P crosses cell membrane & binds to PR. Now the heat shock protein dissociates from the PR. Now the PR +P moves to target gene. Induces mRNA & specific proteins.

ACTIONS OF PROGESTERONE ON THE UTERUS ON THE UTERUS ON THE FALLOPIAN TUBE ON THE FALLOPIAN TUBE ON THE UTERINE CERVIX ON THE UTERINE CERVIX ON THE BREASTS ON THE BREASTS OTHER EFFECTS OTHER EFFECTS

ON THE UTERUS On MYOMETRIUM On MYOMETRIUM HYPERPLASIA HYPERPLASIA ANTIESTROGENIC, BY DECREASING EXCITABILITY, & REDUCING SENSITIVITY OXYTOCIN RECEPTORS PREVENTS ABORTION ANTIESTROGENIC, BY DECREASING EXCITABILITY, & REDUCING SENSITIVITY OXYTOCIN RECEPTORS PREVENTS ABORTION On ENDOMETRIUM ESTROGEN PRIMED ENDOMETRIUM INTO SECRETORY ENDOMETRIUM ESTROGEN PRIMED ENDOMETRIUM INTO SECRETORY ENDOMETRIUM

ON THE FALLOPIAN TUBE DECREASES CONTRACTIONS DECREASES CONTRACTIONS INCREASES MUCUS SECRETION INCREASES MUCUS SECRETION

ON THE UTERINE CERVIX HYPERTROPHY HYPERTROPHY THICK MUCOUS SECRETION DURING SECRETORY PHASE OF MENSTRUAL CYCLE

ON THE BREASTS DEVELOPMENT OF LOBULES & ALVEOLI DEVELOPMENT OF LOBULES & ALVEOLI It induces differentiation of estrogen-prepared ductal tissue and supports the secretory function of the breast during lactation. It induces differentiation of estrogen-prepared ductal tissue and supports the secretory function of the breast during lactation.

OTHER ACTIONS THERMOGENIC THERMOGENIC SLIGHT ANABOLIC SLIGHT ANABOLIC LARGE DOSES CAUSE NATRIURESIS PROBABLY BY BLOCKING ACTION OF ALDOSTERONE ON KIDNEY LARGE DOSES CAUSE NATRIURESIS PROBABLY BY BLOCKING ACTION OF ALDOSTERONE ON KIDNEY FEED BACK REGULATION AT PITUITARY & HYPOTHALAMUS FEED BACK REGULATION AT PITUITARY & HYPOTHALAMUS

RELAXIN PEPTIDE HORMONE PEPTIDE HORMONE PRODUCED BY CORPUS LUTEUM DURING EARLY PREGNANCY & BY PLACENTA IN LATER PHASES. PRODUCED BY CORPUS LUTEUM DURING EARLY PREGNANCY & BY PLACENTA IN LATER PHASES. INHIBITS UTERINE CONTRACTIONS & PREVENTS ABORTION INHIBITS UTERINE CONTRACTIONS & PREVENTS ABORTION RELAXES PUBIC SYMPHYSIS & OTHER PELVIC JOINTS & SOFTENS THE UTERINE CERVIX THUS FACILITATES PARTURITION. RELAXES PUBIC SYMPHYSIS & OTHER PELVIC JOINTS & SOFTENS THE UTERINE CERVIX THUS FACILITATES PARTURITION.

INHIBIN PEPTIDE HORMONE PEPTIDE HORMONE PRODUCED BY GRANULOSA CELLS & CORPUS LUTEUM PRODUCED BY GRANULOSA CELLS & CORPUS LUTEUM FEED BACK INHIBITION OF FSH FEED BACK INHIBITION OF FSH ADMINSTRATION IN EARLY FOLLICULAR PHASE MAY INHIBIT FSH SECR, THERBY PREVENTS FOLLICULOGENESIS & OVULATION ADMINSTRATION IN EARLY FOLLICULAR PHASE MAY INHIBIT FSH SECR, THERBY PREVENTS FOLLICULOGENESIS & OVULATION

Various COMBINATIONS OF ESTROGEN AND PROGESTERONE AS Various COMBINATIONS OF ESTROGEN AND PROGESTERONE AS CONTRACEPTIVE PILLS by preventing maturation of follicles and/or preventing ovulation. (details refer pharmac ) CONTRACEPTIVE PILLS by preventing maturation of follicles and/or preventing ovulation. (details refer pharmac )

REGULATION OF OVARIAN FUNCTION

HYPOTHALMO- PITUITARY- OVARIAN AXIS IN A NORMAL MENSTRUAL CYCLE

OVERALL REGULATION SCHEME OVERALL REGULATION SCHEME ROLE OF HYPOTHALAMUS ROLE OF HYPOTHALAMUS ROLE ANTERIOR PITUITARY ROLE ANTERIOR PITUITARY ROLE OF OVARY ROLE OF OVARY APPLIED ASPECTS APPLIED ASPECTS

HYPOTHALAMIC MEDIAN EMINANCE & ARCUATE NUCLEUS GnRH ANTERIOR PITUITARY LH FSH ESTROGEN PROGESTERONE INHIBIN TARGET ORGANS OVARY + +

GnRH RELEASE PULSATILE PULSATILE FREQUENCY OF PULSES HIGH DURING FOLLICULAR PHASE FREQUENCY OF PULSES HIGH DURING FOLLICULAR PHASE FREQUENCY IS LOW IN LUTEAL PHASE FREQUENCY IS LOW IN LUTEAL PHASE INFLUENCED BY HIGHER CENTERS, ESPECIALLY EMOTIONS INFLUENCED BY HIGHER CENTERS, ESPECIALLY EMOTIONS

Pulsatile secretion of GnRH