VETS2008 lecture 8 - female hormones.pdf

VETS2008 – Female hormones Dr Taylor Pini BAVBS (Hons), PhD [email protected] Learning outcomes for this lecture 1. Identify the major female reproductive hormones, the structure(s) responsible for their synthesis and describe their endpoint actions 2. Explain the HPG axis, including feedb...

VETS2008 – Female hormones Dr Taylor Pini BAVBS (Hons), PhD [email protected] Learning outcomes for this lecture 1. Identify the major female reproductive hormones, the structure(s) responsible for their synthesis and describe their endpoint actions 2. Explain the HPG axis, including feedback mechanisms 3. Explain the expected outcomes of administering exogenous GnRH, gonadotropins, progesterone or PGF2α 2 Active learning links UQ Active eLearning Wordcloud apps.elearning.uq.edu.au/wordcloud/71644 MCQs apps.elearning.uq.edu.au/poll/71644 Active learn ID = 71644 Padlet padletuq.padlet.org/tpini/ao61tbyw6sqqmb01 3 The repro life cycle – where are we today? MALE FEMALE Copulation Estrus Puberty Puberty Fertilisation/preg Male repro tract establishment Female repro tract Embryo/fetal Hormone development Hormone signalling signalling Parturition & Spermato- lactation genesis Oogenesis Post birth 4 Major female repro hormones - Origins Hypothalamic Pituitary Gonadal Uterus/placenta GnRH LH Estradiol (E2) PGF2α Oxytocin FSH Testosterone Progesterone Prolactin Progesterone (P4) (P4) Relaxin Inhibin Chorionic Relaxin gonadotropins Placental lactogen 5 The HPG axis The Hypothalamic Pituitary Gonadal (HPG) axis regulates the production of reproductive hormones in both sexes The HPG axis is connected by vasculature, which delivers hormones to tissues Production of hormones is controlled by positive and negative feedback Tissues can have diff sensitivity to +/- feedback 6  The hypothalamus + pituitary The hypothalamus is a specialised portion of the brain, with clusters of nuclei – three are relevant to repro:  Surge centre [GnRH]  Tonic centre [GnRH] PVN  Para-ventricular nucleus [Oxytocin] Directly connected to the hypothalamus is the pituitary, consisting of:  Anterior pituitary [FSH, LH]  Posterior pituitary 7 GnRH secretion in females The presence of a surge centre in the hypothalamus is the biggest difference between males and females Creates two distinct patterns of GnRH secretion: Tonic (slow drip) Surge (fast flood) The surge of GnRH in turn creates a pre-ovulatory LH surge from the AP 8  The ovary – follicles Gonadotropins act on cells in developing follicles LH binds to LH receptors in Theca interna cells to produce testosterone FSH binds to FSH receptors in Granulosa cells, which drives conversion of T to estradiol 9 Estradiol – 2 cell, 2 gonadotropin model Production of estradiol (aka E2), the major female sex hormone, requires 2 cells and 2 gonadotropins: theca and granulosa cells LH and FSH Estrogen vs estradiol Estradiol (E2) is the major estrogen. Two others, Estrone (E1) and Estriol (E3), exist but have far weaker activity 10 Actions of estradiol E2 produced by developing follicles acts on the: Brain Induces mate seeking behaviours Makes females receptive to mating Female tract Creates outward signs of receptivity (e.g. red, swollen vulva) Primes tract for mating (e.g. mucus/immune cells to protect against infection, thickened vaginal epithelium) Prepares for possible pregnancy (e.g. dev of uterine glands, increased uterine Estradiol is the key tone/motility for sperm transport, cilia beating in hormone for mating oviduct) 11 HPG axis feedback – estradiol Three important negative feedback loops: Inhibin blocks FSH secretion by AP E2 blocks FSH secretion by AP Low E2 + high P4 limits GnRH secretion One important positive feedback loop: High E2 (with no P4) promotes a surge of GnRH at a threshold concentration Feedback mechanisms regulate hormone production – critical to ensure: Follicle maturation Ovulation 12 The ovary – corpus luteum LH binds to LH receptors in luteal cells to produce progesterone (P4) 13 Actions of progesterone P4 produced by the CL acts on the: Mammary glands Promotes development Endometrium Promotes gland development Promotes gland secretion of histotroph Myometrium Decreases uterine tone (contractions) Brain Inhibits receptive behaviours Progesterone is the key hormone for maintaining pregnancy 14 HPG axis feedback – progesterone One important negative feedback loop: Progesterone supresses GnRH secretion by both the surge and tonic centres, also limiting LH  In the tonic centre = reduced pulse frequency  In the surge centre = blocks surges Progesterone will block ovulation, so a CL needs to degenerate before ovulation can occur 15 Hormone secretion patterns Depending on the cycle stage, the level of each hormone differs For now, remember that: E2 is produced by developing follicle(s), and peaks prior to ovulation Rising E2 drives GnRH surge, which causes an LH surge, leading to ovulation After ovulation, a developing CL causes increased P4 16  LH in females vs males Low level LH pulses occur in both males and females In females: Between ovulations, small LH pulses and E2 remains low Prior to ovulation, E2 peaks due to follicle development, causing GnRH and LH surge In males: An LH pulse is followed by a testosterone pulse Test your knowledge Estradiol is produced via the ‘2 cell, 2 gonadotropin’ model. What are the 2 cells and 2 A. Theca interna/granulosa, GnRH/LH gonadotropins involved in B. Theca interna/luteal, FSH/LH producing estradiol? C. Theca interna/granulosa, FSH/LH D. Luteal/granulosa, FSH/LH Use UQ poll to answer: apps.elearning.uq.edu.au/poll/71644 E. Theca interna/luteal, GnRH/LH 18 PGF2α – luteolysis After a given interval, the CL regresses because it undergoes luteolysis In most species, the signal for luteolysis is prostaglandin F2α, a hormone produced by the uterine endometrium and transferred to the ovary by counter-current exchange between the uterine vein and ovarian artery 19 Other relevant hormones Chorionic gonadotropins Gonadotropins produced by the placenta (chorion) Only produced in the woman (hCG) and mare (eCG/PSMG) LH/FSH like activity in other species – used in ARTs Oxytocin Produced in the hypothalamus and the ovary (CL) Positive feedback with PGF2α – drives luteolysis Also stimulates myometrial contractions during parturition Stimulates lactation (milk let down) Relaxin Produced by the placenta and CL Causes softening of pelvic ligaments and cervix for parturition 20 Think-pair-share What would happen if we gave a GnRH agonist to a female once, or multiple times? Why? 21 Think-pair-share What would happen if we gave a female an LH or FSH-like hormone (e.g. equine chorionic gonadotropin)? 22 Think-pair-share What would happen if we gave a female progesterone for an extended period of time? 23 Think-pair-share What would happen if we injected a female with PGF2α? Why? 24 Effects of PGF2α explained 25 Test your knowledge A CL has recently undergone luteolysis and ovulation will occur soon. A. Increasing P4 and E2, decreasing LH B. Increasing P4, decreasing E2, LH surge What does the hormonal profile look like for P4, E2 and LH? C. Decreasing P4, E2 and LH D. Decreasing P4, increasing E2, LH Use UQ poll to answer: surge apps.elearning.uq.edu.au/poll/71644 E. Increasing P4, E2 and LH 26  Summary – female reproductive hormones Hormone Class Origin Target Action GnRH Neuropeptide Hypothalamus Anterior pituitary LH, FSH release LH Glycoprotein Anterior pituitary Theca interna/luteal cells, Ovulation, CL formation, P4 prod granulosa cells FSH Glycoprotein Anterior pituitary Granulosa cells Follicle development, E2 prod Testosterone Steroid Theca interna Granulosa cells E2 prod (substrate) cells Estradiol (E2) Steroid Granulosa cells Hypothalamus, female tract, GnRH surge, sexual behaviour, tract mammary gland secretion, increased uterine motility Progesterone Steroid CL/placenta Endo/myometrium, mammary Increased endometrial secretion, preg main (P4) gland PGF2α Prostaglandin Endometrium CL, myometrium, ovulatory follicles Luteolysis, uterine contraction, ovulation Inhibin Glycoprotein Granulosa cells Anterior pituitary Inhibits FSH release Relaxin Polypeptide CL/placenta Pelvic ligaments, cervix Softening Oxytocin Neuropeptide Hypothalamus/CL Endo/myometrium, mammary Uterine motility, PGF2α prod, milk ejection gland Take home points Major hormones o E2 (follicle – granulosa cells) o P4 (corpus luteum) o PGF2α (endometrium) Multiple feedback mechanisms o +ve feedback of E2 on GnRH/LH o -ve feedback of E2/inhibin on FSH o -ve feedback of P4 on GnRH/LH Providing exogenous hormones o GnRH (single) = support follicle dev or ovulation o FSH/LH (single) = support follicle dev or ovulation o P4 (prolonged) = suppresses GnRH o PGF2α (single) = luteolysis 28 Thanks! Questions? Email: [email protected] Office Hours Chat: ask away now! 29