Progesterone 1 PDF

Estrogen and progesterone I Aikseng Ooi, Ph.D. Skaggs, Room 132 [email protected] slide-1 Main sex steroid hormones are produced at different ratio in men and in women Estradiol (E2) levels Women (18 year old) Women (post menopause) Men (18 + year old) data*) : 17-200 pg/mL : 7-40 pg/mL : 10-...

Estrogen and progesterone I Aikseng Ooi, Ph.D. Skaggs, Room 132 [email protected] slide-1 Main sex steroid hormones are produced at different ratio in men and in women Estradiol (E2) levels Women (18 year old) Women (post menopause) Men (18 + year old) data*) : 17-200 pg/mL : 7-40 pg/mL : 10-60 pg/mL (18 – 40 year old, nonobese, 2017 Progesterone levels Women (pre-ovulation or post menopause): < 1 ng/mL or 3.18 nmol/L Women (mid-cycle): 5 to 20 ng/mL or 15.90 to 63.60 nmol/L Pregnancy 1st trimester: 11.2 to 90.0 ng/mL or 35.62 to 286.20 nmol/L Pregnancy 2nd trimester: 25.6 to 89.4 ng/mL or 81.41 to 284.29 nmol/L Men (adult) : < 1 ng/mL or 3.18 nmol/L Testosterone (T) levels Women (18 + year old) : 8-60 ng/dL Men (18 – 40 year old, nonobese, 2017 data*) : 204 – 904 ng/dL slide-2 The hypothalamic-pituitarygonadal (HPG) axis Hypothalamic gonadotropin-releasing hormone (GnRH) Luteinizing hormone (LH) Follicle-stimulating hormone (FSH) slide-3 ©2007 by National Academy of Sciences J. Larry Jameson PNAS 2007;104:17247-17248 Biosynthesis slide-4 Biosynthesis slide-5 Biosynthesis slide-6 slide-7 Mechanisms of action slide-8 Estrogen receptors are nuclear receptors Progesterone has similar mechanisms slide-9 slide-10 Nature Reviews Cancer 5, 761-772 (October 2005) ERα)and)ERβ)in)the)body)&)CNS) ERα and ERβ in the body & CNS J.A.)Gustafsson) slide-11 Progesterone)receptors) Located)abundantly)in)brain,)pituitary)and) reproduc-ve)tract.))In)the)la_er,) progesterone)acts)to)decrease)penetra-on) Systemic functions of estrogen of)the)cervix)by)sperm.) ) Also)found)in)mammary)gland,)and) progesterone)acts)during)pregnancy)to) prepare)the)gland)for)lacta-on.) slide-12 Major functions of estrogens Females: Puberty: the development of secondary sex characteristics (growth & development of vagina, uterus, fallopian tubes; breast development; fat deposition (specific fat depots); skeletal growth). Adulthood: Ovulation, maintenance of bone mass, metabolism & reproductive tract. slide-13 Android vs gynoid body shape slide-14 Mol Cell Endocrinol. 2015 Feb 15; 0: 113–119. Biosynthesis)of)Estrogens) Major functions of estrogens Males: Pubertal growth and skeletal growth, fat deposition (specific fat depots), skeletal growth EstrogenLiverdeficiencies: gonadal hypertrophy, Ovary Liver increased testosterone levels, and potentially fertility or metabolic abnormalities. Estrogen excess: Gynecomastia, fat accumulation (specific fat depots), obesity slide-15 Compounds)with)estrogenic)ac-vity) Compounds with estrogenic activities E2 slide-16 E1 E3 slide-17 Summary 1. Estrogen, progesterone, and testosterone are steroidal sex hormones. 2. GnRH à LH, FSH à sex steroid hormone. Sex steroids form feed back loop to suppress GnRH release. 3. Cholesterol is the precursor of steroid hormone synthesis. 4. Different steps and enzymes in steroidal synthesis and degradation. 5. Mechanism of action of steroid hormones. 6. Estrogen and tissue specific effects. 7. Estrogen receptors and estrogenic compounds. slide-18 Progestins slide-19 Progesterone receptors are nuclear receptors slide-20 Proges-ns) Progesterone) Progestins – Most)important)proges-n) Progesterone Precursor)to)estrogens,)androgens,)and)adrenocor-cal) –– Most important progestin steroids.) – Precursor to estrogens, androgens, and adrenocortical steroids. Progesterone)is)synthesized)from)cholesterol)in)ovary) )(corpus)luteum),)tes-s,)adrenal,)and)in)placenta.) Progesterone is synthesized from cholesterol in ovary (corpus luteum), testis, adrenal gland, High)dose)micronized)prepara-on)is)required)due)to) and in placenta. )almost)complete)metabolism)in)first)passage) ) )through)the)liver.) High dose micronized preparation is required due to almost complete metabolism in first passage through the liver. slide-21 Progesterone)and)progesta-onal) Progestins agents) slide-22 Major functions of progesterone Females: Preparation of the uterus for pregnancy; maintenance of pregnancy; suppression of menstruation and uterine contractility during pregnancy. Males: May be inhibitory to spermatogenesis; sometimes used as a contraceptive. slide-23 Progesterone effects: many oppose the effects of estrogen Stimulates lipoprotein lipase activity and favors fat deposition Increases body temperature Increases ventilatory response to CO2 Has depressant effects Causes maturation of endometrium to a secretory stage and decreases estrogen-driven proliferation Increases nitrogen excretion Cervical secretions are thick and lowered in pH Supports pregnancy by suppressing menstruation and uterine contractions In breast, triggers single round of mitotic activity each cycle and ductal development slide-24 Estrogen and progesterone in the menstrual cycle slide-25 Estrogen and progesterone in menstrual cycle slide-26 4/20/15 Estrogen and progesterone in menstrual cycle Menstrual Cycle: -Hormonal changes Menstrual)Cycle:) -Uterine endometrial ) changes CHormonal)changes) CUterine)endometrial)changes) -Follicular changes CFollicular)changes) Goodman & Gilman (2001) Fig. 58-3 Goodman)&)Gilman)(2001))Fig.)58C3) slide-27 Changes in the reproductive tract Changes)in)the)reproduc-ve)tract)during) during the menstrual cycle the)menstrual)cycle) -Estrogen levels increase during the follicular phase: CEstrogen))levels)increase)during)the)follicular)phase:)this)results)in) the)prolifera-on)of)the)uterine)endometrium.) this results in the proliferation of the uterine ) endometrium. CProgesterone)increases)during)the)luteal)phase)(from)the)corpus) -Progesterone increases during the luteal phase (from luteum)[CL]):)this)causes)epithelial)cell)secre-ons)that)are) necessary)for)blastocyst)implanta-on,)should)fer-liza-on)occur.) the corpus luteum [CL]): this causes epithelial cell ) secretions that are necessary for blastocyst CIf)fer-liza-on)does)not)occur,)the)CL)regresses,)and)the) endometrium)is)shed)(menstrua-on).) implantation, should fertilization occur. ) -If fertilization does not occur, the CL regresses, and the CIf)fer-liza-on)does)occur,)the)CL)is)maintained,)hCG)produc-on) endometrium is shed (menstruation). from)the)blastocyst)(and)later)placenta))increases)and)E)and)P) levels)are)maintained.) -If fertilization does occur, the CL is maintained, hCG production from the blastocyst (and later placenta) increases and E and P levels are maintained. slide-28 8 Summary 1. HPG axis maintain sex hormone levels 1. GnRH à LH and FSH 1. LH and FSH à sex hormone production 1. Estrogen and progesterone initiate and maintain secondary sex characteristics and metabolism 1. Estrogen and progesterone play important roles in the menstrual cycle slide-29