1. Reproductive Endocrinology and the Menstrual Cycle Flashcards
What are steroids, and what is the central core molecule?
List the common steroid hormones. What causes their differences from each other?
Differentiate between the type of oestrogen molecule.
Lipids, 27 C skeleton with 4 fused rings, small and lipophilic, central core molecule = cholesterol
Oestrogens (oestradiol, oestriol, osterone), progesterone, testosterone. Different due to functional groups attaching to the 4 ring structre
Oestrone (E1): intermediate, Oestradiol (E2): most well known and referred to as oestrogen, Oestriol (E3): in pregnancy only. Numbers indicate numbers of OH groups
Whre are the following steroids synthesised in males and females?
a) testosterone
b) dihydrotestosterone (DHT)
c) progesterone
d) oestradiol
e) androstenedione
f) dehydroepiandrosterone (DHEA)
a) Males: Leydig cells (testes). Females: Thecal cells (ovary)(25%), adrenals (25%), peripheral coverstion in adipose tissue (50%)
b) Males: from testosterone in Sertoli cells (testes) and target tissues. Females: from testosterone
c) Males: adrenals. Females: corpus luteum (ovary), syncytiotrophoblasts (placenta), (adrenals as intermediate)
d) Males: from testosterone (depending on aromatase presence e.g. adipose tissue). Females: Granulosa cells (ovary), from testosterone, syncytiotrophoblasts (placenta)
e) Males: Leydig cells, adrenals. Females: ovary (50%), adrenals (50%)
f) Males: Leydig cells, adrenals. Females: ovary (20%), adrenals (80%)
What does steroid synthesis require, and what is the first step for the production of all steroid hormones?
Describe steroid synthesis in males.
Oxidative enzymes in mitochondria and endoplasmic reticulum. 1st step: cholesterol -> pregnenolone
GnRH (hypothalamus) stimulates FSH and LH from anterior pituitary. LH stimulates testosterone production from Leydig cells. Main target of testosterone and FSH are Sertoli cells, where 5α reductase converts testosterone -> DHT. Sertoli cells then secrete androgen binding protein (ABP) which binds to and carries testosterone to the seminiferous tubule where it stimulates spermatogenesis.
Describe steroid synthesis in females.
What do androgens (DHT, testosterone, androstenedione, DHEA) do?
What is the most potent androgen?
GnRH -> LH. LH stimulates testosterone production by theca cells in ovarian follicle. Testosterone enters granulosa cells (surrounding oocyte) and is converted by aromatase to oestrogen. Oestradiol stimulates LH receptor formation on granulosa cells enabling the follicle to respond to LH surge, thus giving rise to ovulation.
Maintain male somatic tissue differentation, induce male 20 sexual characteristics, support spermatogenesis, influence sexual/aggressive behaviour (male and female), promote protein anabolism, somatic growth and ossification, regulate gonadotrophin secretion (testosterone), induce body hair (in females - pubic and axillary)
DHT
What do oestrogens do? What is the most potent form?
What does progesterone do?
What are the most important glycoproteins?
Stimulate growth of mammay glands and endometrium, induce female 20 sexual characteristics, prepare uterus for spermatozoa transport, increase vascular permeability, mildly anabolic, regulate gonadotrophin secretion, invovled in Ca homeostasis. Most potent: 17b oestradiol
Luteal progesterone prepares endometrium for implantation during the secretory phase of menstral cycle. Affects cervix, vagina and breast. Placental progesterone maintains endometrium (decidua) in pregnancy (after around 10-12w).
LH, FSH (and hCG)
What glycoproteins do the following produce:
a) anterior pituitary (gonadotrophs)
b) placenta (syncytiotrophoblasts)
Describe the structure of a gonadotroph.
Which 2 gonadotrophins contain the same sequence of AAs in the β subunit and thus stimulate the same receptor?
a) LH, FSH. (TSH)
b) hCG
2 glycoproteins form the functional glycoprotein and are called the α and β subunits. α identical in FSH, LH, hCH (and TSH) and is 92 AAs. β different in each and confers specific biological action.
LH and hCG but the hCG β subunit has an additional 24 AAs (so can give infertile males hCG)
What do the following do:
a) FSH
b) LH
c) hCG
a) stimulate growth of immature Graafian follicles (ovary) to maturity. Enhances production of ABP by Sertoli cells of testes and needed for spermatogenesis.
b) surge = ovulation trigger and converts residual follicle into corpus luteum. Maintains luteal function. Stimulates thecal cells in ovary to produce testosterone for oestradiol production. Acts upon Leydig cells of testis and responsible for testosterone production.
c) Maintains corpus luteum in pregnancy
What glycoprotein inhibits FSH release?
What glycoprotein increases FSH activity?
List some peptides. Why do they have short T1/2?
What is the menstrual cycle? What are the 3 stages?
Inhibin
Activin
GnRH (hypothalamus), GHRH (hypothalmus), oxytocin (hypothalamus), prolactin (anterior pituitary). So effect is not continuous.
Series of cyclic changes in the uterine endometrium occuring on a monthly basis IRT changes in levels of ovarian hormones. Menstural phase (1-5 days), proliferative phase (6-14 days), secretory phase (15-28 days). Always basal layer that remains, functional layer (top) removed.
Describe phase 1 of the menstrual cycle.
Describe phase 2 of the menstrual cycle.
Describe phase 3 of the menstrual cycle.
Menstrual phase. 1-5 days. Withdrawal of steroid support of oestrogen and progesterone -> endometrium collapses and is shed with blood (50-150ml) from ruptured arteries (spinal arteries contract to reduce bleeding), pass through vagina.
Proliferative phase. 6-14 days. Oestrogen from mature follicle stimulates thickening of endometrium, glands and spiral arteries form. Oestrogen stimuates synthesis of progesterone receptors on endometrial cells.
Secretory phase. 15-28 days. Progesterone from corpus luteum acts on endometrium and stimulates enlargement of glands which secrete mucus and glycogen in preparation for implantation of the fertilised oocyte. CL degenerates if no fertilisation -> progesterone levels fall and endometerium degenerates and cycle starts again.
What stage of the menstrual cycle is shown here?
Endometrium: onset of mensturation.
What stage of the menstrual cycle is shown here?
Proliferative endometrium with lots of glands forming.
What stage of the menstrual cycle is shown here?
Secretory endometrium. Big cells and glands secreting components for incoming foetus
What happens if fertilisation does not occur?
What happens if fertilisation occurs?
Corpus luteum degenerates and forms corpus albicans, progesteron falls, endometrium breaks down, mensturation occurs.
Blastocyst implants into maternal endometrium. Developing placenta secretes hCG which stops corpus leuteum degenerating (binds to LH receptors on CL), and thus maintains progesterone levels, which maintains the endometrium
