Reproduction/Sex steroid axis: physiology and Biochemistry

Question 1

what 2 pituitary hormones are important in reproduction?

Answer 1

“gonadotropic hormones”
FSH (stimulates follicles)
LH (stimulates corpus luteum production)

Question 2

what does FSH do?

Answer 2

regulates spermatogenesis

causes growth of ovarian follicles (oogenesis) and causes ovary to secrete oestrogen

Question 3

what does LH do?

Answer 3

causes testes to secrete testosterone

causes ovulation and it causes progesterone production by the corpus luteum

Question 4

what controls secretion of gonadrotrophin releasing hormone from the hypothalamus?

Answer 4

sex hormone levels
testosterone = exerts negative feedback
oestrogen = can exert both positive and negative feedback depending on levels
progesterone = always exerts negative feedback

Question 5

what does gonadotrophin releasing hormone do?

Answer 5

responsible for release of FSH and LH from the anterior pituitary

Question 6

what is GnRH and how is it released?

Answer 6

neuropeptide hormone synthesised and released from GnRH neurons within the hypothalamus
released in a pulsatile manner

Question 7

how GnRH release vary in males and females?

Answer 7

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)

Question 8

which pulses causes secretion of what?

Answer 8

high frequency GnRH release stimulates LH

low frequency = FSH release

Question 9

what drives the release of LH?

Answer 9

oestrogen concentrations above a certain threshold will increase GnRH pulsatility which drives LH secretion

Question 10

what controls the pulsatility of GnRH?

Answer 10

high oestrogen = increased GnRH release

high progesterone = reduced GnRH

Question 11

modulation of which pulse frequency is most important for pubertal maturation and reproductive function?

Answer 11

LH

Question 12

how is GnRH pulse frequency involved in onset of puberty?

Answer 12

onset is associated with steady acceleration in GnRH pulsatility
activation of the GnRH pulse frequency is associated in delayed puberty

Question 13

what can abnormalities in GnRH result in?

Answer 13

associated with reproductive disorders (anovulation, amenorrhoea etc)

Question 14

how do oestrogen and progesterone influence the hypothalamus?

Answer 14

no receptor for oestrogen or progesterone in GnRH producing neurons in the hypothalamus
therefore regulated by kisspeptin

Question 15

what are the 2 phases of the menstrual cycle?

Answer 15

follicular phase (AKA proliferative phase)
luteal phase (AKA secretory phase)

Question 16

what is the follicular phase?

Answer 16

variable length (14 +/- 7 days long)
characterised by follicular growth

Question 17

what is the luteal phase?

Answer 17

more constant length (14 days)

corpus luteam production and secretion of hormones from the corpus luteum

Question 18

describe the hormonal changes which occur in the female cycle?

Answer 18

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

Question 19

what is a follicle?

Answer 19

oocyte surrounded by follicular cells (granulosa cells, theca cells)

Question 20

what is involved in follicular growth?

Answer 20

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

Question 21

what happens to the endometrium during the 28 day cycle?

Answer 21

endometrium thickens under influence of oestrogen and becomes a secretory tissue under influence of progesterone

Question 22

what are the components of a follicle?

Answer 22

oocyte
zone pellucida
zone granulosa
antrum
theca interna

Question 23

what does LH do and where?

Answer 23

stimulates conversion of cholesterol to androgen in theca cells

Question 24

what does FSH do and where?

Answer 24

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

Question 25

what determines the availability of follicles in later life?

Answer 25

number of primordial follicles present in primordial pool at birth
7 million > 2 million at birth > 0.5 million at puberty

Question 26

how do follicles develop?

Answer 26

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)

Question 27

how is dominant follicle selected?

Answer 27

only one equipped to cope with the drop which occurs in FSH once oestrogen levels rise due to negative feedback
- e.g best vasculature

Question 28

how can the timing of ovulation be predicted in a cycle?

Answer 28

on basis of LH surge (surge precedes ovulation by 34-36 hrs)

Question 29

what is required for the LH surge?

Answer 29

threshold of oestrogen = 200pg/ml (under this oestrogen gives negative feedback instead of positive feedback)

Question 30

why is increasing LH levels important for ovulation?

Answer 30

increasing LH causes increased progesterone which stimulates expression of enzymes that help breakdown the follicular wall leading to release of oocyte

Question 31

how is the corpus luteum formed?

Answer 31

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

Question 32

what do oestrogens do?

Answer 32

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)

Question 33

what does progesterone do?

Answer 33

maintains thickness of endometrium
responsible for infertile thick mucous
relaxes myometrium

Question 34

factors in sperm genesis?

Answer 34

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

Question 35

what cells are involved in spermatogenesis?

Answer 35

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

Question 36

where are sperm formed?

Answer 36

between Sertoli cells in the seminiferous tubules

Question 37

what does testosterone do in spermatogenesis?

Answer 37

taken up by Sertoli cells
maintains integrity of the blood-testes barrier
influences peritubular myoid cells causing release of mature spermatozoa from Sertoli cells

Question 38

describe the compartments in testicular organisation

Answer 38

extratubular compartment = outside of seminiferous tubules(interstitial and intravascular compartment)
intratubular = inside seminiferous tubules (basal and luminal compartments)

Question 39

what hormones are involved in spermatogenesis?

Answer 39

endocrine - LH and FSH

paracrine - testosterone and inhibin