ENDO - Overview of Reproductive Endocrinology Flashcards
Describe the hypothalamo-pituitary-gonadal axis.
- Gonadotrophs - found in anterior pituitary - contain GnRH receptors (GPCRs).
- Activation of the GnRH receptor leads to an increase in intracellular calcium and subsequent exocytosis of stored LH and FSH vesicles
- Gonadotrophs are also regulated by negative feedback from oestrogen.
- They contain nuclear oestrogen receptors, activation of which leads to an increase in the expression of delayed rectifier potassium channels, which increase K+ efflux and thus hyperpolarise the cell, preventing further exocytosis.
Gondatrophs nnervated by GnRH neurons (hypothalamic arcuate nucleus)
What are the two main cell types in testicular lobules?
Sertoli
Leydig
Describe Leydig cells.
- LH binds to LH receptors on the cell surface, which causes an increase in intracellular cAMP.
- Increase in the translocation of cholesterol into the mitochondria, where enzymes catalyse its formation into pregnenalone.
- Pregnenalone then either stays in the mitochondria or moves to the ER where it is further metabolised to testosterone
Under the influence of LH
Describe Sertoli cells. PART 1
- Sertoli cells respond to FSH via the FSH receptor.
- Activation of the FSH receptor leads to an increase in cAMP and exocytosis of androgen binding proteins into the seminiferous fluid of the lumen.
- These ABPs are responsible for increasing the concentration of testosterone in the seminiferous fluid so it is available to spermatogonium to aid in spermatogenesis
Describe Sertoli cells. PART 2
- Sertoli cells also have testosterone receptors (remember testosterone is coming from the neighbouring Leydig cells), activation of which increases the expression of various genes associated with aiding spermatogenesis.
- FSH is also responsible for increasing testicular size during puberty as it stimulates Sertoli cell proliferation
Label the diagram on slide 8.
Describe the steps leading up to secondary follicle development.
- Women are born with around 400,000 primordial follicles. These are arrested in an early mitotic phase.
- Each menstrual cycle, around 20 cells mature into primary follicles (although only one of these will usually ovulate).
- During this phase, a small layer of granulosa cells begins to form. These express FSH receptors, and the maturation into a secondary follicle is stimulated by FSH.
Label the diagram on slide 9.
Describe granulosa cells
- Antrum is a follicular fluid secreted by granulosa cells – contains high levels of oestrogen
- Granulosa cells are under the influence of FSH, which stimulates more granulosa cells to be produced.
- Theca cells are under the influence of LH (which at this stage is released at much lower concentrations than FSH).
- LH stimulates theca cells to produce pre-androgens, which then move to granulosa cells which have the aromatase enzyme necessary to convert them into oestrogens
Look at the graph on slide 10.
What happens to oestrogen levels as FSH and LH levels rise and what is the effect of this ?
(b) Similarly, look at the graph on slide 12. What happens past the oestrogen threshold?
- As FSH and LH levels rise, so too does the amount of oestrogen produced by the follicle
- Stimulates the endometrium to thicken in anticipation of the arrival of an egg
- At a particular threshold of oestrogen, for reasons not yet known the previous negative feedback that oestrogen has on LH and FSH secretion becomes positive, leading to a spike in LH and FSH secretion just prior to ovulation
What is the effect of the surge of FSH and LH?
Look at the graph on slide 14 - what do you notice happens to progesterone secretion following this effect?
- Converts the theca and granulosa cells from oestrogen synthesising to progesterone synthesising.
- LH also causes the cells of the theca externa to produce proteolytic enzymes, which weaken the wall of the follicle and ovary, allowing ovulation to occur
- Significant spike in progesterone secretion after ovulation
What happens to the granulosa and theca cells following ovulation?
- Turn into lutein cells - characterised by an increase in lipid droplet composition.
- Mediated by LH
- Corpus luteum grows to around 1.5cm in diameter and releases large amounts of progesterone
What is the effect of progesterone on the uterine walls?
Increase the thickness of the uterine wall and increase the vascularisation.
- Essential for implantation and zygote survival
What happens to the zygote if fertilisation were to occur/not occur?
- If a sperm and egg fertilise the resulting zygote secretes large amounts of hCG, which signals to the corpus luteum to maintain its secretion of progesterone.
- If fertilisation does not occur, the lack of hCG signals the corpus luteum to degrade.
- Subsequent loss of progesterone results in shedding of the uterine lining, and given its highly vascularised nature, this results in bleeding seen during menstruation
Look at the graph on slide 18. Describe what happens at the end of the graph.
- Reduction in oestrogen and progesterone that occurs at the end of a cycle removes the negative feedback on LH and FSH secretion, meaning the whole cycle can start again.
- The phase prior to ovulation is known as the follicular phase.
- The phase following ovulation is known as the luteal phase.
