Reproduction/Sex steroid axis: physiology and Biochemistry Flashcards
what 2 pituitary hormones are important in reproduction?
“gonadotropic hormones”
FSH (stimulates follicles)
LH (stimulates corpus luteum production)
what does FSH do?
regulates spermatogenesis
causes growth of ovarian follicles (oogenesis) and causes ovary to secrete oestrogen
what does LH do?
causes testes to secrete testosterone
causes ovulation and it causes progesterone production by the corpus luteum
what controls secretion of gonadrotrophin releasing hormone from the hypothalamus?
sex hormone levels
testosterone = exerts negative feedback
oestrogen = can exert both positive and negative feedback depending on levels
progesterone = always exerts negative feedback
what does gonadotrophin releasing hormone do?
responsible for release of FSH and LH from the anterior pituitary
what is GnRH and how is it released?
neuropeptide hormone synthesised and released from GnRH neurons within the hypothalamus
released in a pulsatile manner
how GnRH release vary in males and females?
males = released in pulses at a constant frequency females = frequency in pulses varies during menstrual cycle (every 1-2 hrs during early follicular phase, decreases in frequency in late follicular phase and decreases to every 4 hrs during luteal phase)
which pulses causes secretion of what?
high frequency GnRH release stimulates LH
low frequency = FSH release
what drives the release of LH?
oestrogen concentrations above a certain threshold will increase GnRH pulsatility which drives LH secretion
what controls the pulsatility of GnRH?
high oestrogen = increased GnRH release
high progesterone = reduced GnRH
modulation of which pulse frequency is most important for pubertal maturation and reproductive function?
LH
how is GnRH pulse frequency involved in onset of puberty?
onset is associated with steady acceleration in GnRH pulsatility
activation of the GnRH pulse frequency is associated in delayed puberty
what can abnormalities in GnRH result in?
associated with reproductive disorders (anovulation, amenorrhoea etc)
how do oestrogen and progesterone influence the hypothalamus?
no receptor for oestrogen or progesterone in GnRH producing neurons in the hypothalamus
therefore regulated by kisspeptin
what are the 2 phases of the menstrual cycle?
follicular phase (AKA proliferative phase) luteal phase (AKA secretory phase)
what is the follicular phase?
variable length (14 +/- 7 days long) characterised by follicular growth
what is the luteal phase?
more constant length (14 days)
corpus luteam production and secretion of hormones from the corpus luteum
describe the hormonal changes which occur in the female cycle?
FSH > follicle growth > rising oestrogen > negative feedback > reduced FSH > oestrogen rises above threshold > positive feedback > increased FSH and “LH surge” > LH surge drives ovulation and regulation of corpus luteum and secretion of progesterone > increased progesterone > decreased GnRH pulsatility > decreased LH
what is a follicle?
oocyte surrounded by follicular cells (granulosa cells, theca cells)
what is involved in follicular growth?
increase in number of follicular cells (not oocytes) and accumulation of follicular fluid both resulting in an increase in the diameter and overall size of the follicle
what happens to the endometrium during the 28 day cycle?
endometrium thickens under influence of oestrogen and becomes a secretory tissue under influence of progesterone
what are the components of a follicle?
oocyte zone pellucida zone granulosa antrum theca interna
what does LH do and where?
stimulates conversion of cholesterol to androgen in theca cells
what does FSH do and where?
stimulates conversion of androgen to oestrogen in granulosa cells (involved aromatase)
occurs in granulosa cell
- i.e if low FSH - cant convert androgens made in thecal cells so get high androgens
what determines the availability of follicles in later life?
number of primordial follicles present in primordial pool at birth
7 million > 2 million at birth > 0.5 million at puberty
how do follicles develop?
early stages of growth don’t need gonadrotrophins
once it reaches a certain size (2-5mm) it needs gonadotrophin (if this doesn’t coincide with rise in FSH during early follicular phase then the follicle is lost)
number of follicles will continue to grow under influence of FSH but only 1 (dominant follicle) will be selected for ovulation (totally dependant on FSH levels)
how is dominant follicle selected?
only one equipped to cope with the drop which occurs in FSH once oestrogen levels rise due to negative feedback
- e.g best vasculature
how can the timing of ovulation be predicted in a cycle?
on basis of LH surge (surge precedes ovulation by 34-36 hrs)
what is required for the LH surge?
threshold of oestrogen = 200pg/ml (under this oestrogen gives negative feedback instead of positive feedback)
why is increasing LH levels important for ovulation?
increasing LH causes increased progesterone which stimulates expression of enzymes that help breakdown the follicular wall leading to release of oocyte
how is the corpus luteum formed?
occurs under the influence of LH
follicle that has been ovulated is stimulated to become the corpus luteum
LH stimulates angiogenesis which ensures delivery of cholesterol from blood which is the substrate for progesterone synthesis
full of cholesterol - allows it to churn out progesterone
granulosa and theca cells transform into luteal cells
what do oestrogens do?
increase thickness of vaginal wall
regulate LH release
reduce vaginal Ph through increase in lactic acid production
decease viscosity of cervical mucous to facilitate sperm penetration (progesterone does the opposite)
what does progesterone do?
maintains thickness of endometrium
responsible for infertile thick mucous
relaxes myometrium
factors in sperm genesis?
spermatogenesis
occurs in testes
under endocrine comtrol (LH, FSH, testosterone)
takes 70 days overall
100 sperm made per heartbeat
begins at puberty and occurs for 60 years
need to be highly motile to successfully reach egg
what cells are involved in spermatogenesis?
spermatogonia > primary spermatocyte > crosses into adluminal compartment > meiosis 1 > 2 secondary spermatocytes > meiosis 2 > 4 spermatids > spermiogenesis > 4 spermatozoa > matures into 4 sperm cells in the epididimis
where are sperm formed?
between Sertoli cells in the seminiferous tubules
what does testosterone do in spermatogenesis?
taken up by Sertoli cells
maintains integrity of the blood-testes barrier
influences peritubular myoid cells causing release of mature spermatozoa from Sertoli cells
describe the compartments in testicular organisation
extratubular compartment = outside of seminiferous tubules(interstitial and intravascular compartment)
intratubular = inside seminiferous tubules (basal and luminal compartments)
what hormones are involved in spermatogenesis?
endocrine - LH and FSH
paracrine - testosterone and inhibin
