Overview Introduction Female hormones in follicular phase of menstrual cycle, follicle synthesizes estrogens major product is 17β-estradiol in luteal phase of menstrual cycle, corpus luteum synthesizes progesterone and estrogen major product is progesterone Estrogen Sources of estrogens ovary (17β-estradiol) placenta (estriol) blood (aromatization) Estrogens biosynthesis two-cell, two-gonadotropin model 17β-estradiol synthesis requires granulosa cells and theca cells theca cells do not express aromatase aromatase catalyzes conversion of androstenedione to 17β-estradiol biosynthetic pathway LH acts on theca cells increases activity of cholesterol desmolase increases synthesis/secretion of androstenedione androstenedione freely diffuses from theca cells to granulosa cells FSH acts on granulosa cells increases activity of aromatase increases synthesis/secretion of 17β-estradiol Estrogens potency 17β-estradiol > estrone > estriol Estrogen receptor estrogen receptor (ER) functions as a homodimer and resides in cell cytoplasm estrogen-ER complex translocates to cell nucleus, interacts with steroid response elements on chromatin, and rapidly induces transcription of target genes Function of estrogens at puberty, functions in development of female sex characteristics genitalia, breasts, and female fat distribution functions in proliferation and development of ovarian granulosa cells of follicles functions in maturation and maintenance of uterus proliferates endometrium of uterus lowers uterine threshold to contractile stimuli increases myometrial excitability upregulates estrogen, progesterone, and LH receptors negatively feeds back on anterior pituitary in follicular phase of menstrual cycle ↓ FSH and ↓ LH positively feeds back on anterior pituitary at midcycle in response to LH surge ↑ FSH and ↑ LH stimulates prolactin secretion blocks action of prolactin on breasts upregulates transport proteins in blood plasma, estrogens are mostly bound to carrier proteins e.g., albumin and sex hormone-binding globulin (SHBG) upregulates HDL cholesterol and downregulates LDL cholesterol Notes pregnancy 50-fold ↑ in 17β-estradiol and estrone 1,000-fold ↑ in estriol increase in estriol levels is an indicator of well-being of fetus Progesterone Sources of progesterone corpus luteum, placenta, adrenal cortex, and testes Function of progesterone stimulates endometrial glandular secretions stimulates development of spiral arteries maintains pregnancy raises uterine threshold to contractile stimuli during pregnancy decreases myometrial excitability relaxes uterine smooth muscle prevents contractions produces thick cervical mucus that inhibits sperm entry into uterus increases basal body temperature increases hypothalamic temperature set-point negatively feeds back on anterior pituitary in luteal phase of menstrual cycle ↓ FSH and ↓ LH downregulates estrogen receptors Notes increase in biosynthesis of progesterone is characteristic of mid cycle or ovulation "PROGESTerone is PRO-GESTation" Estrogen and Progesterone in Pregnancy Overview estriol is major estrogen in pregnancy Maternal-placental-fetal unit elevated levels of estrogens and progesterone are necessary for maintaining pregnancy corpus luteum is not adequate to generate very high hormone levels placenta emerges as major source of estrogens and progesterone placenta is an imperfect endocrine organ placenta cannot synthesize sufficient cholesterol cholesterol is a precursor for hormone synthesis placenta lacks necessary enzymes for estrogen synthesis maternal-placental-fetal unit overcomes shortcomings of placenta to very high hormones levels Progesterone synthesis mother provides cholesterol (LDL particles) to placenta placenta converts cholesterol to pregnenolone then to progesterone placenta provides high progesterone levels to mother Estriol synthesis mother provides cholesterol (LDL particles) to placenta placenta converts cholesterol to pregnenolone to progesterone placenta provides high progesterone levels to fetus fetal adrenal cortex converts progesterone to DHEA-sulfate fetal liver hydroxylates DHEA-sulfate to 16-OH DHEA-sulfate fetus provides high levels of 16-OH DHEA-sulfate to placenta placenta converts 16-OH DHEA-sulfate to estriol placenta provides high estriol levels to mother