reproductive endocrinology Flashcards
what are the 2 groups of molecules involved in the menstrual cycle?
steroids
glycoproteins
what are steroids?
• Lipids with a 27 carbon skeleton
- contains four fused rings with a variety of groups attached
what are properties of steroids
small
lipophilic
why do steroids need to be lipophilic?
pass through cell membrane via simple diffusion and bind to their receptor which can be nuclear or cytoplasmic
what is the central core molecule to all steroids?
cholesterol
why are steroids, oestrogens, progesterone and testosterone different?
differences are due to functional groups attached to the four-ring structure.
why do males and females have different amounts of oestrogen and testosterone?
different number of receptors for each
what do binding globulins do?
binds to testosterone and stops it being metabolised
what affects the levels of binding globulins?
levels of oestrogens and thyroids hormones
what are the oestrogen molecules and describe their structures?
oestrone - 1x OH molecule on the end
oestradiol - 2x OH molecules
oestriol - 3x OH molecules
where are Leydig cells found?
outside the seminiferous tubules
where are Sertoli cells found?
found inside the seminiferous tubules
where are thecal cells found?
in the ovaries surrounding the oocyte
where is testosterone made in males and females?
males: Leydig cells (testes)
females: thecal cells (35%), adrenals (25%), peripheral conversion in adipose tissue (50%)
where is DHT made in males and females?
males: conversion from testosterone in Sertoli cells (testes) and target tissues
females: peripheral conversion from testosterone
where is progesterone made in males and females?
males: adrenals
females: corpus luteum (ovary), syncytiotrophoblasts (placenta), adrenals as an intermediate
where is oestradiol made in males and females?
males: peripheral conversion from testosterone (depending on presence of aromatase) e.g. adipose tissue
females: granulosa cells, peripheral conversion from testosterone, syncytiotrophoblasts
where is Andostenedione made in males and females?
males: Leydig cells, adrenals
females: ovary (50%), adrenals (50%)
where is DHEA made in males and females?
males: Leydig cells, adrenals
females: ovary (20%), adrenals (80%)
what enzymes does synthesis of steroids depend and where are these found?
Synthesis requires oxidative enzymes located in mitochondria and ER
what is the first step in the synthesis of steroids?
conversion of cholesterol –> pregnenolone
what does GnRH in hypothalamus stimulate?
FSH and luteinising hormone (LH) secretion by anterior pituitary.
what role does LH have in steroid synthesis in males?
stimulates testosterone production by Leydig cells
what cells do testosterone and pituitary FSH target?
Sertoli cells
what does the enzyme 5a reductase do?
converts testosterone to DHT in Sertoli cells
how do Sertoli cells stimulate to spermatogenesis?
- enzyme 5a reductase converts testosterone to DHT
- Sertoli cells then secrete androgen binding protein (ABDP)
- Binds to testosterone + carries it to seminiferous tubule where it stimulates spermatogenesis
what does LH do in steroid synthesis in females?
• LH stimulates testosterone production by theca cells in the ovarian follicle
how does LH stimulate ovulation?
• LH stimulates testosterone production by theca cells in the ovarian follicle.
• Testosterone enters granulosa cells (surround oocyte) where it’s converted by aromatase into oestrogen (mainly 17-beta oestradiol)
• Oestradiol: stimulates formation of LH receptors on granulosa cells.
- Enables follicle to response to LH surge –> ovulation.
describe the 2 stage model of oestrogen synthesis?
- Androgen precursors are synthesised in the outer layer (theca cells) of the ovarian follicles –> Driven by LH
- Diffuse into inner layer (granulosa cells) for conversion to oestrogens –> Driven by FSH
what do androgens do?
- Maintain male somatic tissue differentiation
- Induce male secondary sexual characteristics
- Support spermatogenesis
- Influence sexual and aggressive behaviour (male & female)
- Promote protein anabolism, somatic growth & ossification
- Regulate gonadotrophin secretion (testosterone)
- Induce body hair (in females – pubic & axillary)
what do oestrogens do?
- Stimulate growth of mammary gland + endometrium (mucous membrane in uterus).
- Induce female secondary sexually characteristics.
- Prepare uterus for spermatozoa transport
- Increase vascular permeability
- Mildly anabolic
- Regulate gonadotrophin secretion
what does luteal progesterone prepare?
prepares endometrium for implantation during the secondary phase of the menstrual cycle
what body parts do progestagens affect?
cervix, vagina and breast
what does placental progesterone do?
maintains endometrium (decidua) in pregnancy after 10-12 weeks.
what are glycoproteins?
contain oligosaccharide chains covalently attached to polypeptide side-chains
where are glycoproteins produced?
anterior pituitary
placenta
where are gonadotrophs produced and by what cell?
anterior pituitary
gonadotrophic cells
what are the gonadotrophs?
- Luteinising hormone (LH)
- Follicle stimulating hormone (FSH)
- Thryotrophs (TSH)
what cells produce glycoproteins in the placenta?
syncytiotrophoblast cells (epithelial covering of placental villi)
what glycoproteins are produced by the placenta?
• Human chorionic gonadotrophin (hCG).
describe the structure of gonadotrophins?
2 glycosylated proteins together form functional glycoprotein - alpha and beta subunits.
Alpha - 92 amino acids
beta - different
what glycoproteins is the alpha subunit identical in?
FSH, LH and hCG
how is the beta subunit different in LH and hCG?
o Beta subunit of LH/hCG have the same sequence of aa, stimulate same receptor. However, hCG has an additional 24 amino acids
what does FSH do in females?
stimulates the growth of immature Graafian follicles in the ovary to maturity
what does FSH do in males?
enhances production of androgen-binding protein by Sertoli cells of testes and is needed for spermatogenesis
what does a surge in LH trigger?
ovulation
what does LH do?
- Converts residual follicle corpus luteum.
- Maintains the luteal phase (latter phase of the menstrual cycle).
- Stimulates thecal cells in the ovary to produce testosterone for Oestradiol production (female)
- Acts upon Leydig cells of the testis + is responsible for the production of testosterone (male)
what does hCG do?
maintains corpus luteum in pregnancy
what produces inhibin in males?
Sertoli cells
what does inhibin do when sperm count is high?
inhibin secretion increases and inhibits pituitary release of FSH, hypothalamic release of GnRH.
at what sperm count does inhibin secretion decrease?
<20
what cells produce inhibin in females?
Granulosa cells
what does inhibin do in females?
helps exert negative control on FSH production during menstrual cycle
what is activin?
a glycoprotein of the transforming growth factor beta family
what does activin do?
Increases FSH activity, enhances the actions of LH in both males and females
when is relaxin produced in females?
produced during menstrual cycle (follicular development & oocyte maturation) and pregnancy (relaxation of ligaments and parturition).
when is relaxin produced in males?
in seminal fluid to enhance sperm motility
name peptides, the number of amino acids and the location of peptides?
- Gonadotrophin releasing hormone: 10 aa, HYPOTHALAMUS
- Growth hormone releasing hormone: 44 aa, HYPOTHALAMUS
- Oxytocin: 9aa, HYPOTHALAMUS
- Prolactin: 198 aa, ANTERIOR PITUITARY
what is the menstrual cycle
Series of cyclic changes in the uterine endometrium
Occurs monthly in response to changes in levels of ovarian hormones
what are the stages of the menstrual cycle?
menstrual phase
proliferative phase
secretory phase
what happens in the menstrual phase?
- Due to withdrawal of steroid support (oestrogen/progesterone) the endometrium collapses.
- Endometrium is shed with blood from ruptured arteries (spiral arteries contract to reduce bleeding) (blood loss: 50-150ml).
- Detached endometrial tissue and blood passes through vagina as menstrual flow
when is the menstrual phase?
day 1-5
what happens in the proliferative phase?
- Oestrogen from mature follicle stimulates thickening of the endometrium.
- Glands/spinal arteries form.
- Oestrogen also causes the growth of progesterone receptors on endometrial cells
when is the proliferative phase?
days 6-14
what happens in the secretory phase?
- Progesterone from corpus luteum acts on endometrium.
- Progesterone also stimulates enlargement of glands secrete mucus and glycogen in preparation for implantation of fertilised oocyte.
- No fertilisation = corpus luteum degenerates –> corpus albicans. Progesterone levels fall and the endometrium degenerates.
- Cycles then starts again with the first day of menstrual flow
when is the secretory phase?
day 15 - 28
what is fertilisation?
Fertilisation is when the blastocyst implants onto the maternal endometrium
what happens if fertilisation does not occur?
- Corpus luteum degenerates and forms the corpus albicans.
- Progesterone levels fall.
- Endometrium breaks down.
- Menstruation occurs.
what happens if fertilisation does occur?
- Blastocyst implants into maternal endometrium
- Developing placenta secretes hCG
- Corpus luteum does not degenerate due to hCG.
- Progesterone levels do not fall because progesterone secretion is maintained by the corpus luteum.
- Progesterone maintains the endometrium.