Male Reproduction Flashcards
Hypothalamic-pituitary-gonadal axis: from start to finish
o Hypothalamus: pulse generator releases gonadotropin releasing hormone (GRH) → portal system → Pituitary, where it stimulates the production & secretion of LH and FSH →
• FSH: stimulates follicules in ovary & spermatogenesis in testis
• LH: stimulates estrogen production in ovary & testosterone production in the testis
What kind of feedback do you get in hypthalmic/pituitary/ gonadal axis?
o Products of the gonads (steroids i.e. testosterone, estrogen, progesterone) feedback to suppress the GRH pulse generator
• Note that estrogen can also do positive feedback in women!
o Inhibin: from testes and ovarys → does negative feedback to stop FSH release
o GNRH neurons don’t express sex steroid receptors; it’s mediated by other neurons around the GNRH neurons that act upon the GNRH neurons i.e. kisspeptin, glutamate, GABA, TE, CRH neurons
Role of kisspeptin
• Kisspeptin neuron is next to GNRH neuron & GPR54 receptor is on GNRH neurons & stimulates GNRH
o Critical signal for normal puberty
o Mediates positive and negative feedback of steroids on GNRH neurons
o Kiss1 receptors on ARC do negative feedback on males and females
o AVPV has Kiss1 receptors that do positive feedback & are more common in females, which helps explain the sexual dimorphism where estrogen does positive feedback in females
What happens if GNRH is not secreted in a pulsatile manner?
Pulsatile release of GNRH leads to pulsatile release of LH and FSH
If it’s released continuiously as in IV infusion, release of LH and FSH are suppressed
In this way, GNRH can be used as an LH and FSH antagonist
What else affects gonadal axis?
o Endogenous opioids (beta-endorphin) suppresses pulsatile LH secretion on hypothalamus level
o CRH: suppresses the gonadal axis and stimulates adrenal axis (cortisol)
• CRH + naloxone (opioid antagonist) – you don’t block stimulation of adrenal axis but you block the suppression of the gonadal axis
o Stress: suppresses testosterone secretion in men
• In women this is easier: stress → amenorrhea
• In men, you have to stress them more: i.e. very sick
• 24 hour pattern of plasma LH and Testosterone:
o Pulses in LH and testosterone = variability in different parts of the day
o Unlike the menstrual cycle, which is less pulsatile than male axis
• Males sex development: from Y chromosome to hormones/organs
o Y chromosome → gonadal primordium/testis determining factor (TDF) → shuts of the default which is development of ovaries
o Testes develops 2 types of cells:
- Sertoli cells: anti-Mullerian hormone → mullerian duct regression
- Without testes, you won’t get mullerian duct regression → get female tract
- Leydig cells: testosterone
- Wolffian ducts → epididymis, vas deferens, seminal vesicles
- Dihydrotestosterone → penis, scrotum
Which 2 hormones can testosterone be converted to? What are the reaction?
Cna be reduced to dihydrotestosterone (DHT)
Aromatization gives you estrogen
- all estrogen comes from testosterone in both men and women!
Which receptor does DHT bind?
o Both testosterone and DHT bind to the same nuclear receptors but have diff affinities/interacting factors → different transcription/translation
o It’s critical to get DHT binding at certain points of development to get normal male
What’s DHT necessary for?
Necessary for prostate and penis
o Deficiency → have testes but abnormal development of prostate & penis/ ambiguous genitalia
o Since they have testes, during puberty that make all the necessary hormones
Changes in plasma testosterone levels during male sexual development?
o Gestation: highest at 2nd trimester
o Zero at birth
o Peak during neonatal period
o Zero from age 1 until puberty
o Slowly rises and reaches a max/plateau from age 17 until adulthood
o Slowly comes down during aging i.e. after age 80
LH secretion and puberty:
o Prepunerty: pulsatile
o Puberty: high levels during sleep
o Adult pattern: continuous pulsatile pattern in the night and in the day
• Sequence of changes during male puberty
o First sign is testis growth
o Second is penis growth
o Third is height spurt
o There’s also pubic hair growth, but some is from adrenal androgens and some is from testicular androgens
What accounts for the testicular growth?
• Testicular growth: 1-6 mL pre-pubertal to 15-25 mL adult size
o Increase in volume is mostly due to seminiferous tubules which do spermatogenesis & are made from sertoli cells
What do sertoli cells do?
Spermatogenesis
• Make androgen binding protein which binds testosterone & increases the conc in the cell
They are columnar cells that line the seminiferous tubules
