Reproductive Axis Flashcards
Which hormone does the hypothalamus secrete in control of the reproductive axis?
Gonadotropin releasing hormone (GnRH)
Name the two gonadotropic hormones secreted by the anterior pituitary in response to GnRH
Follicle stimulating hormone (FSH)
Luteinising hormone (LH)
What is the function of FSH and LH in males? (1 for each)
FSH: causes the testes to produce sperm (spermatogenesis)
LH: causes the testes to secrete testosterone
What is the function of FSH and LH in females? (2 for each)
FSH:
- causes growth of ovarian follicles (oogenesis)
- causes ovaries to secrete oestrogen
LH:
- causes ovulation
- causes progesterone production by the corpus luteum
Which cells in the hypothalamus secrete GnRH?
GnRH neurons
Which of the following is true: GnRH is released from GnRH neurons... - diurnally - in a pulsatile manner - overnight ?
In a pulsatile manner
How is GnRH release regulated?
Oestrogen and progesterone act on kisspeptin neurons which act on GnRH neurons (both in the hypothalamus)
This regulates frequency of GnRH release
Oestrogen causes high/low frequency GnRH pulses
Progesterone causes high/low frequency GnRH pulses
Oestrogen causes high frequency GnRH pulses
Progesterone causes low frequency GnRH pulses
High frequency GnRH pulses cause FSH/LH release
Low frequency GnRH pulses cause FSH/LH release
High frequency GnRH pulses cause LH release
Low frequency GnRH pulses cause FSH release
How does frequency of GnRH pulses differ between males and females?
Males: GnRH pulses at constant frequency
Females: Frequency of GnRH pulses varies during menstrual cycle
Describe the two phases of the menstrual cycle
Follicular phase:
- FSH causes follicles to grow and secrete oestrogen
- Once threshold of oestrogen is crossed, LH surge at end of phase causes ovulation
- Length of this phase can vary
Luteal phase:
- LH causes the corpus luteum to produce progesterone
- Length of this phase is fixed at ~14 days
- Progesterone peak ~half way through
Describe GnRH pulse frequency in the follicular phase of the menstrual cycle
- FSH release is high at first, stimulating follicle growth
- Growing follicle produces oestrogen which increases frequency of GnRH pulses
- Increased GnRH frequency increases LH secretion and reduces FSH secretion
- LH surge causes ovulation
Describe GnRH pulse frequency in the luteal phase of the menstrual cycle
- Corpus luteum produces progesterone
- This reduces GnRH pulse frequency which lowers LH and increases FSH secretion
How does FSH cause the follicle to grow? (2)
- Increases number of follicular cells surrounding the oocyte
- Increases accumulation of follicular fluid
How do oestrogen and progesterone affect the endometrium itself?
Follicular phase: Increased oestrogen thickens the endometrium
Luteal phase: Increased progesterone makes the endometrium a secretory tissue (important for egg implantation)
Name the specialised follicle cells surrounding an oocyte which LH and FSH act on
Which hormone acts on which cell?
LH acts on outer Theca cells
FSH acts on inner Granulosa cells
Describe the function of theca cells
Convert cholesterol to androgens under the influence of LH
Describe the function of granulosa cells
Convert the androgens from the theca cells to oestrogens under the influence of FSH
Which enzyme converts androgens to oestrogens in granulosa cells?
Aromatase
Number of follicles in the ovaries increases up until puberty. T/F
False
Primordial pool of follicles in each ovary forms before birth
The number of follicles decreases up to puberty -
Primordial pool: 7 million
Birth: 2 million
Puberty: 0.5 million
Early stages of follicle growth are gonadotropin-independent. When does follicle growth start the rely on FSH?
When it forms a fluid-filled antrum (when it’s ~2-5mm diameter)
How many follicles grow under the influence of FSH per cycle?
~7
Why does only 1 growing follicle take part in ovulation?
Dip in FSH at time of LH surge means that only the dominant follicle goes through ovulation as it can cope with the FSH decrease
What features of the dominant follicle make it most likely to survive the FSH decrease? (3)
- Largest
- Most FSH receptors
- Highest vascularity
How can tracking the LH surge be helpful in IVF treatment?
LH surge precedes ovulation by ~34-36 hours
In IVF, the follicles should be removed after the LH surge but before release of the oocyte
Formation of the corpus luteum occurs under the influence of LH/FSH?
LH
What happens to granulosa and theca cells during the luteal phase?
They lose their specialisation and all become luteal cells
What is the function of luteal cells?
Convert cholesterol to progesterone
How does LH increase progesterone secretion from the corpus luteum? (2)
- Stimulates angiogenesis which diverts cholesterol to the corpus luteum (to be used as a substrate for progesterone synthesis)
- Stimulates enzymes involved in conversion of cholesterol to progesterone
When LH drops once the egg has implanted, which hormone takes over control of progesterone production from the corpus luteum?
hCG produced by the embryo
hCG = human chorionic gonadotropin
List 4 functions of oestrogens in females
- Increases thickness of vaginal wall (to support implantation)
- Regulates LH surge
- Reduces vaginal pH through increased lactic acid production
- Decreases viscosity of cervical mucous to facilitate sperm penetration
List 3 functions of progesterone in females
hint: “pro-gestation”
- Maintains thickness of endometrium
- Responsible for infertile, thick mucous (to prevent sperm transport and prevent infection)
- Relaxes the myometrium (smooth muscle of the uterus)
How is progesterone thought to regulate birth?
Functional withdrawal of progesterone is thought to regulate smooth muscle contractions of the myometrium
How is rigidity (i.e., width) of the cervical canal determined?
By collagen in the cervical wall
Which cells of the cervical canal produce cervical mucus?
Columnar epithelium cells
A sperm’s ability to penetrate cervical mucus is regulated by… (4)
- Thickness of mucus (hormonal control)
- Motility of sperm (less mobile sperm will get stuck)
- Interaction with reactive oxygen species produced by leukocytes in the mucus
- Interactions with mucins
The cervix also contains primary and secondary grooves which do not lead to the uterus. Why might this help select the best sperm for reproduction?
Weaker sperm will swim into the grooves to avoid the thick mucus and immune cells in the cervical canal
Which hormones are involved in spermatogenesis?
LH, FSH and testosterone
How many days does it take to complete spermatogenesis?
~70 days
Spermatogenesis begins in the womb and continues for 60+ years. T/F
False
Spermatogenesis first occurs at puberty and continues for 60+ years
Humans produce ~1000 sperm per... - Heartbeat - Minute - Hour - Day ?
Heartbeat
Describe the structure of the seminiferous tubules in the testes
Seminiferous tubules contain Sertoli cells and maturing germ cells
Surrounded by an extra tubular compartment of interstitial tissue i.e., Leydig cells, blood vessels, immune cells
As the spermatocytes undergo spermatogenesis, they move from the outside/inside to the inside/outside of the tubule
As the spermatocytes undergo spermatogenesis, they move from the outside to the inside of the tubule
How does FSH influence spermatogenesis?
FSH stimulates sertoli cells in the seminiferous tubules to drive spermatogenesis and produce androgen binding globulin (ABG)
(fSh, Sertoli cells, Spermatogenesis)
How does LH influence spermatogenesis?
LH stimulates Leydig cells in the interstitium to produce testosterone
How does the testosterone produced by Leydig cells influence spermatogenesis?
It crosses the blood-testes barrier, enters the seminiferous tubules and is taken up by sertoli cells for spermatogenesis (90%)
It also maintains the integrity of the blood-testes barrier
The other 10% of testosterone is released into circulation
Why is testosterone content in the testes 25-125x greater than in the serum?
Testosterone binds to androgen binding globulin (ABG) produced by sertoli cells
What is meant by ‘the blood-testes barrier’?
A layer of peritubular myoid cells that separate the seminiferous tubules from the interstitium
What is the function of the blood-testes barrier?
It separates sperm from immune cells in the blood stream
Why should immune cells be separated from the sperm?
Sperm are not produced till puberty so may be recognised as foreign cells, resulting in inflammation of the testes