Lecture 30: Hormone control of male and female reproduction Flashcards
Describe the hormone control of reproduction
GnRH from the hypothalamus causes the release of FSH and LH from the anterior pituitary gland
What is the target organ for LH and FSH?
the gonads
LH and FSH act together to affect what two processes?
gametogenesis
steroidogenesis
What is gametogenesis (specific to males and females)?
sperm production in the testes and ova development in the ovary
What is steroidgenesis?
hormone production
What are the two male hormones produced?
testosterone and inhibin
What are the three female hormones produced?
estrogen, progesterone and inhibin
What does HPG stand for?
hypothalamo-pituitary-gonadal
Describe the HPG axis
There are GnRH neurons in the hypothalamus which project to the ME where they terminate. Here they release GnRH which stimulates the release of LH/FSH from the anterior pituitary gland. These act on the gonads and cause them to release estrogen, progesterone and testosterone
Do the hormones released from the gonads cause positive or negative feedback to the hypothalamus?
it depends
In what way is GnRH released?
in a pulsatile way
Inside the scrotum, there is what two things?
the seminiferous tubules and the interstitium
What percentage of the scrotum is made up of seminiferous tubules?
80%
What percent of the scrotum is made up of the interstitium?
20%
What is in the interstitium?
Leydig cells
What is the main role of the Leydig cells?
to produce testosterone
What is the main role of the seminiferous tubules?
to produce sperm
What the support/nursing cell in the seminiferous tubules?
the Sertoli cells
The sperm are produced in the seminiferous tubules and stored where?
in the epididymis
Describe the process of sperm production
There is a precursor (spermatogonium) which differentiates and matured into a spermatocyte, spermatid and spermatozoa
In the hormonal control of male reproduction, which hormone is released from the hypothalamus?
GnRH
In the hormonal control of male reproduction, GnRH is released from the hypothalamus and stimulates the release of what from the anterior pituitary gland?
LH and FSH
In the hormonal control of male reproduction, what does FSH do?
this acts on the Sertoli cells to stimulate the release of inhibin and to stimulate spermatogenesis
In the hormonal control of male reproduction, what does LH do? What is the effect of this?
this acts on the Leydig cells and causes them to release testosterone which acts locally on the sertoli cells and enters the blood
What is the effect of inhibin?
this acts in a short negative feedback loop to stop the release of FSH from the anterior pituitary gland
What is the effect of testosterone?
- it locally affects the ____________ cells
- it is causes a response to testosterone from the ___________ ____________ and other ___________
- it acts in both a ___________ negative feedback loop to to the release of ___________ from the anterior pituitary gland, and a long negative feedback loop to stop the release of _____________ from the ______________
- it locally affects the Sertoli cells
- it is causes a response to testosterone from the reproductive tract and other organs
- it acts in both a short negative feedback loop to to the release of LH from the anterior pituitary gland, and a long negative feedback loop to stop the release of GnRH from the hypothalamus
Describe how LH affects the Leydig cells
LH binds to the LH receptor on the Leydig cells and activates a G-protein. There is activation of cAMP which activates PKA and this causes new proteins to be synthesised. This produces new enzymes to be formed that can convert cholesterol to testosterone (in the Leydig cells)
Where does the testosterone produced in the Leydig cells go?
it can to the the seminiferous tubules to the Sertoli cells
Describe how FSH affects the Sertoli cells
FSH binds to the FSH receptor on the Sertoli cells which activates a G-protein. There is activation of cAMP which activates PKA and this causes new proteins to be synthesised. This produces things like inhibins, ABPs, growth factors and aromatase
What is important about aromatase that is produced by Sertoli cells?
They convert the testosterone from the Leydig cells into estradiol
What is the affect of estradiol in the male reproduction?
it affects the Leydig cells to affect testosterone production
How does testosterone affect the cell?
Testosterone enters the cell and is converted to the more potent 5α-dihydrotestosterone (5α reductase) inside the cell. This binds to an androgen receptor. Two of these complexes join together and enter the nucleus to get protein expression
How does the testosterone secretion change throughout the day?
it is pulsatile throughout the day but it the mean level is higher between midnight and noon
How does the testosterone secretion change in a lifetime?
The embryo produces a little bit and then it increases which reflects the masculinisation of the embryo. Then it drops off before birth. There is a post-natal spike and then at puberty it vastly increases and is held steady until about 60yrs when it begins to decline
Is testosterone produced by the sertoli cell?
no
Is testosterone synthesised from cholesterol?
yes
Are testosterone levels constant throughout the life of a male?
no
Can testosterone be converted to an estrogen?
yes
What is the main reproductive organ of the female?
the uterus
What is the role of the uterus?
for protection of the embryo and for nutritional support
Where does the oocyte (if fertilised) implant?
in the endometrium
Describe the follicular development
Each 2 million primordial follicle contains one oocyte. This matures into a primary, secondary and finally a tertiary follicle
Describe the tertiary follicle
It is one oocyte surrounded by granulosa and theca cells
What happens to the follicle after ovulation occurs?
the corpus luteum forms
How many primordial follicles are reserved at menarche?
300,000
Of the 300,000 primordial follicles that are reserved at menarche, how many of them undergo atresia?
about 270,000
What is atresia?
it is programmed cell death
Of the 30,000 primordial follicles that develop into primary, secondary or tertiary follicles, how many of them undergo atresia?
Just under 30,000
After all the atresia, how many follicles are left to be dominant follicles?
about 450
After ovulation, the follicle _________ and the ________ cells enlarge to form the _______ ______________
collapses
granulosa
corpus luteum
The corpus luteum secretes what three hormones?
estrogen, progesterone and inhibin
If fertilisation does not occur, what happens to the corpus luteum?
it degenerates which takes about 10 days
Corpus luteum degeneration leads to what?
menstruation
What are the two phases and what happens in each of these phases?
the follicular phase when the follicle develops
the luteal phase when the corpus luteum is active
Is the follicular phase before or after ovulation?
it is before
Is the luteal phase before or after ovulation?
it is after
Describe the hormonal control of ovarian function during early and middle follicular phase
The hypothalamus secretes GnRH which causes the release of FSH and LH from the anterior pituitary gland. FSH affects the granulosa cells and causes them to release inhibin. LH affects the theca cells and causes them to release oestrogen which impacts the granulosa cells and the reproductive tract and other organs
What is the effect of inhibin?
it is part of a short negative feedback loop which stops the release of FSH from the anterior pituitary gland
What is the effect of estragen?
it is part of a short negative feedback loop which stops the release of LH from the anterior pituitary gland, and is part of a long negative feedback loop which stops the secretion of GnRH from the hypothalamus
What happens when LH binds to a theca cell?
The binding of LH onto a receptor on a theca cell activates a G-protein. This activates cyclic AMP which causes the conversion of cholesterol to pregnenolone. This is then converted to progesterone and them to an intermediate and then to androstenedione and then to testosterone
Why can estradiol not be made in the theca cell?
because there is no aromatase to convert testosterone to estradiol or convert androstenedione to estradiol (via estrone)
Where does the androstenedione go from the theca cell? What happens to it?
it travels to the granulosa cell to be converted into testosterone or estradiol
What happens when LH binds to the GRANULOSA cell?
When LH binds to the granulosa cell, there is activation of a G-protein which activated PKA which converts cholesterol to pregnenelone and then this is converted to progesterone.
Why can androstenedione not be made from progesterone in the granulosa cells?
Because there is no 17-α hydroxylase enzyme to make this conversion
Aromatase synthesis to convert androstenedione to estradiol is facilitated by which hormone?
FSH when it binds to the granulosa cells
How long is the follicular phase?
about 15 days
What does the follicular phase start with?
the menstrual phase
During which phase is the endometrium thickening?
in the follicular phase to it is highest during the luteal phase (and then shed during the menstrual phase)
Describe the hormonal control of the menstrual cycle at the beginning of the follicular phase
there is low estrogen which means that the levels of LH and FSH increase and multiple follicles develop
After many follicles develop, what rises?
the oestrogen level
After the oestrogen level rises, what does the dominant follicle do?
it secretes oestrogen and inhibin
What does the increase oestrogen and inhibin from the dominant follicle do?
it reduces the FSH
What does reduced FSH cause?
oestrogen being switched to positive feedback
When oestrogen is positively feeding back, what happens?
there is an LH surge and ovulation
What happens after ovulation?
the corpus luteum forms
What does the corpus luteum secrete?
it secretes oestrogen and progesterone
What does the oestrogen and progesterone secreted from the corpus luteum do?
it inhibits FSH and LH
When FSH and LH are inhibited, the corpus luteum degenerates. What does this cause?
oestrogen and progesterone levels decrease
What do the decreased levels of oestrogen and progesterone cause?
FSH and LH to rise and the cycle starts again
What cells are involved in the oestrogen switch to positive feedback?
Kisspeptin cells
What does the pill contain?
synthetic oestrogen and progesterone
What is the purpose of the pill?
- prevent ________ by maintaining _________ feedback
- make the __________ less likely to accept ___________
- thicken the ___________ in the cervix
- prevent ovulation by maintaining negative feedback
- make the uterus less likely to accept implantation
- thicken the mucus in the cervix
What 5 things might oral contraceptives influence?
coagulation, increase the risk of deep vein thrombosis, pulmonary embolism, stroke and myocardial infarction
After fertilisation, there is cleavage of the conceptus. This means that all cells are what?
totipotent
At which stage (day 4-7) do cells begin to differentiate?
the blastocyst stage
What is a trophoblast?
The outer cell layer which will be involved in nutrition and secretion of hormones
If there is an inner cell mass and fluid filled cavity, the inner cell mass becomes the what?
the embryo and then the foetus
After how many days does implantation occur?
day 7
there is embedding of the blastocyst into the endometrium
How long does a normal human pregnancy last?
40 weeks
During the last weeks of pregnancy, the cervix becomes soft and flexible due to what?
the breakup of the collagen fibres
Coordination of contractions is possible because of what?
gap junctions between smooth muscle cells that greatly increase near the end of pregnancy
Which hormone is responsible for milk synthesis?
prolactin
Which hormone is responsible for milk ejection?
oxytocin
How is the secretion of prolactin controlled after suckling?
Due to suckling, there is activation of neurons and via the spinal cord, there is a nervous long-loop negative feedback system. This means that this nervous input inhibits the tubero-infundibular dopamine neurons so that no dopamine is released an this allows prolactin to be released from the anterior pituitary gland which stimulates milk synthesis
Describe the milk ejection reflex
Due to suckling, there is activation of neurons and via the spinal cord, there is a nervous long-loop positive feedback system. This activates neurons in the SON/PVN which causes the release of oxytocin from the posterior pituitary gland to stimulate milk ejection
What is cholesterol converted to in the theca cells?
testosterone
What is cholesterol converted to in the granulosa cells?
estradiol
What two hormones can the granulosa cell bind to?
LH and FSH
What happens to the progesterone made in the granulosa cells?
it can travel to the theca cell and help with production of testosterone
Which cell can progesterone not be converted into testosterone? Why is this?
In the granulosa cell because it doesn’t contain the 17-α hydroxylase enzyme which converts progesterone to androstenedione (which then can go on and become testosterone)
