Exam 1 - Male Reproductive Endocrinology Flashcards
Besides germ cells (developing sperm), what are the other types of cells in the testis? Describe their location. What are their main functions?
Sertoli - within the seminiferous tubules, in between the spermatocytes
- nurse cells that support spermatogenesis
Leydig - in between the seminiferous tubules/intersitial
- produce testosterone
Unlike the ovary, sertoli cells have tight junctions that make up the —- —– ——.
blood testis barrier
What stimulates the Leydig cells? What is the overall result?
- LH binds to LH receptors on the Leydig cells
- androgen biosynthesis - stimulates the conversion of cholesterol into pregnenolone (eventually into testosterone)
What happens to the androgens synthesized by Leydig cells?
they diffuse across the Leydig cell membrane into the interstitial spaces, Sertoli cells, and systemic circulation
Describe the biosynthesis pathway of androgens.
cholesterol uses LH and cholesterol side-chain cleavage to become pregnenolone
Pregnenolone either becomes progesterone or uses 17a-hydroxylase to become 17 OH Pregnenolone
17 OH Pregnenolone —> DHEA —> Androstenediol or Androstenedione
Progesterone —> (uses 17a-hydroxylase) 17 OH Progesterone —> Androstenedione
Androstenediol and Androstenedione can become Testosterone
Testosterone uses either:
- 5a reductase to become DHT
- Aromatase to become Estradiol
What are the androgens?
Testosterone (T) - produced in greatest quantity by the testes, 95% comes from the testis and the other 5% from the adrenal cortex
Less potent than testosterone:
Dehydroepiandrosterone (DHEA)
Androstendione (Andro)
Dihydrotestosterone (DHT)
In general, how are androgens transported? Why?
carrier proteins - since steroid hormones are hydrophobic, carrier proteins increase the solubility of steroid hormones and decrease clearance rate
How is testosterone circulated in the bloodstream?
60% bound to sex hormone binding globulin (SHBG) produced by the liver
25% bound to albumin produced by the liver
15% unbound (free)
- only free testosterone is biologically active and able to enter the cell to activate receptors
What hormone stimulates the Sertoli cells? What are the effects of this hormone stimulation?
FSH binds to FSH receptors on the Sertoli cells
FSH stimulates mitosis of spermatogonia, spermiation (release of sperm into the lumen), produce androgen binding protein (ABP), and synthesize/secrete inhibin
What is inhibin?
member of TGFBeta hormone family, inhibits AP from secreting FSH (but not LH)
What does androgen binding protein (ABP) do?
maintain high testosterone levels in the seminiferous tubule (200x greater here than in general circulation) near the developing germ cells
What is the different between ABP and SHBG?
same amino acid sequence, but ABP is produced by the testes and the two cannot cross the blood testis barrier (so they stay in their respective locations)
Besides the effects of FSH, what else do the Sertoli cells do?
maintain the blood testis barrier - form the tight junctions between cells that create an immune barrier
phagocytize abnormal sperm and excess cytoplasm
secrete fluid that nourishes sperm/provides transport medium
Describe the association between Leydig and Sertoli cells. What do each of them produce when stimulated by a AP hormone, and what crosses between the cells?
Leydig cells:
LH activates cAMP, protein kinases, which convert cholesterol to pregnenolone and eventually testosterone. Testosterone diffuses out (into the extracellular space) and across to the Sertoli cells.
Sertoli cells:
FSH activates cAMP which supports spermiation, mitosis of spermatogonia, creation of inhibin, and creation of ABP. ABP binds the testosterone from the Leydig cells, trapping it in the Sertoli cells.
What is the difference in testosterone concentration inside the seminiferous tubule vs. in the systemic circulation/extracellular fluid? Why?
200x higher in the tubule due to ABP production which traps it inside (ABP cant cross/move out)
Most testosterone in the sytemic circulation is carried by…
which allows…
SHBG
more testosterone to remain in the blood that would if it was all free
What mechanism occurs when testosterone enters a cell (like skeletal muscle or hair follicle)? What is the result?
testosterone either remains as testosterone or is turned into DHT by 5a-reductase
Both of them bind to a receptor and form a hormone-receptor complex
hormone-receptor complex acts as a transcription factor to modulate the rate of transcription of steroid hormone-responsive genes
this either induces or represses gene transcription to produce a desired cellular response
What are the 3 general types of effects of testosterone can have in adults?
reproductive, anabolic, and androgenic
What are the reproductive effects of testosterone in adults?
maintenance of internal reproductive tract
required for spermatogenesis (must be 200x higher in tubule)
What form of testosterone produces anabolic effects?
What are the anabolic effects?
testosterone
increased skeletal muscle mass and increased red blood cell production
What form of testosterone produces androgenic effects?
What are the androgenic effects?
DHT
increased libido
sebum formation by the sebaceous glands (acne)
facial hair growth
male-pattern baldness (androgenic alopecia in those who are genetically predisposed)
What type of feedback does inhibin have, and on what tissue?
negative feedback to the anterior pituitary for FSH production (increase inhibin, decrease FSH)
What types of feedback do the androgens have, and on what tissues?
negative feedback to the anterior pituitary for production of LH and FSH
negative feedback to the hypothalamus via KiSS peptin neurons for production of GnRH
Describe how KiSS1 neurons stimulate the adult reproductive axis.
Kiss1 neurons express androgen receptors
Androgens bind and regulate KiSS expression (less androgens = more KiSS expression)
Receptors for kisspeptin are on the GnRH neurons
KiSS stimulation triggers the release of GnRH, which stimulates the pituitary to release LH and FSH
less androgens –> kiss stimulation –> GnRH release –> more FSH and LH –> more androgens
