Male reproductive endocrinology week 3 Flashcards
Between Sertoli and Leydig cells, which are more numerous in seminferous tubules?
Which of the two cell types is the main regulator of sperm differentiation?
- Sertoli to Leydig: 80 % to 20%
- Sertoli cells
What is contained within the head piece of sperm? The tail?
- Head contains the genetic material
- The middle piece contains mitochondria which provide the ATP to power the motility produced by the “tail” of the sperm
Following spermatogenesis, sperm that initially enter the epididymis lack motility and are incapable of fertilization.
List and state the locations of the processes sperm must undergo to fertilize an ovum.
maturation (epididymis)
capacitation (female reproductive tract)
activation (uterine tube)
Explain the process of maturation. What molecules are involved? What is this process dependent upon?
Maturation (in testes)
a. Sperm begin to acquire motility as they pass from the rete testis through the vasa efferentia and epididymis to the vas deferens
b. Acquisition of motility is dependent on the intracellular pH rising and Ca2+ entering the sperm
c. Other changes occur to acrosomal morphology
d. Maturational changes dependent on androgens (with a possible role for estrogen which is also produced in the male)
Explain the process of capacitation. (What occurs, what is involved)
Capacitation (in female reproductive tract)
a. Occurs in the female reproductive tract
b. May result from something found in the estrogen-primed female reproductive tract
c. More likely to involve removal of glycoprotein “decapacitation factor”(acquired in the epididymis) from the outer membrane of the head
d. Motility increases still more as proton channels in the sperm membrane open and result in an additional outward movement of H+ ions (pH inside sperm increases further)
Explain the process of activation. (What occurs, what is involved)
Activation (near the egg)
a. Occurs in oviduct
b. Sperm become hypermotile
c. This is dependent on Ca2+ entering the sperm and H+ leaving
d. Surface membrane of the sperm fuses with the acrosomal membrane (the acrosome reaction)
e. Membrane over the middle and posterior half of sperm head becomes capable of fusing with the egg membrane
f. Motile activity of sperm changes pattern to one that moves the sperm forward along the oviduct to the egg
What cells within testicles produce testosterone? What hormone stimulates testosterone production?
What is the mechanism of action of testosterone?
What are the biological responses of testosterone?
What are the 2 other biologically active andorgens?
Production
- Biosynthesis - two “parallel” pathways to get to testosterone from cholesterol (the precursor)
- Production of androgens in adrenal cortex of minimal importance
- Production of androgens (testosterone) in testes provides major source
- Two other biological active androgens (DHT and 5α androstanediol) are produced in peripheral tissues from testosterone
- Mode of action of androgens on target cells is like that of all of the steroid hormones; binding to intracellular receptors and then modifying translation and transcription.
What is testosterone converted to in the fat, liver, CNS, prostate, scrotum, penis, and bone? What enzymes are required?
How do the liver and kidneys rid of testosterone?
Note that the liver and kidney play a role in determining plasma testerone concentration by excretion of testosterone.
Effects of testosterone on male reproductive system and other systems. The effects are very widespread so that deficiency or excess of testosterone has serious consequences for reproductive and many other functions.
TAKE HOME MESSAGE Testosterone is essential for all male sex functions, but it also has widespread effects on all body systems. It also plays a role in female sexual function.
Explain the negative feedback involved in control of testerone, LH, FSH, and GnRH. (what molecules inhibit, where they act, etc.)
Gonadotropin regulation in males
- There are no positive feedback mechanisms in the male (although there are in the female, as we will see later)
- Negative feedback by testosterone on LH release from anterior pituitary
a. Frequency, but not amplitude, of LH pulses is decreased by testosterone
b. Since frequency of LH pulses is directly determined by frequency of GnRH pulses, this suggests that the negative feedback is on the hypothalamus (the source of GnRH).
c. There are a large number of testosterone receptors on cells in pituitary, suggesting that feedback also occurs onto pituitary - The negative feedback of testosterone on FSH secretion from anterior pituitary is weaker than the inhibition of LH
- FSH secretion is strongly inhibited by inhibin (from Sertoli cells)
a. Effect is at level of pituitary since GnRH levels are unchanged
What hormone is the iniation of spermatogenesis dependent upon?
What hormone is the maintenance of spermatogenesis dependent upon?
- Initiation of spermatogenesis (and repackaging) requires presence of FSH
- Maintenance of spermatogenesis requires testosterone
What is the chemical class of FSH?
What cells have receptors for FSH? Where is the receptor located?
What are the cellular effects of FSH binding to these receptors?
What inhibits the release of FSH?
FSH receptors are found only on Sertoli cells. Responses to FSH include the following:
a. Stimulation of cAMP, activation of the usual cascade of events that lead to increased protein synthesis (including synthesis of androgen-binding protein—ABP)
b. This increased metabolic activity leads to swelling of the Sertoli cell and an increase in secretion of testicular fluid
c. Spermatogenesis can now proceed to completion (if testosterone is present)
d. FSH level is affected by negative feedback of inhibin acting on the pituitary
What is the chemical class of LH?
What cells have receptors for LH? Where is the receptor located?
What are the cellular effects of LH binding to these receptors?
What inhibits the release of LH?
- Production of testosterone is dependent on the presence of LH
- Leydig cells have LH receptors and respond to LH by:
a. Increasing production of cAMP followed by increased testosterone production within 20-30 minutes
b. The testosterone that is released diffuses into the circulation and results in negative feedback on hypothalamic release of GnRH and pituitary release of LH
Explain a paracrine effect of testerone produced in Leydig cells diffusing to Sertoli cells.
Testosterone produced in the Leydig cells also diffuses directly to neighboring Sertoli cells producing paracrine effects such as promoting the production of ABP. ABP binds testerone and its function is though to be to keep testerone levels high.
What is the pattern of release of GnRH? How does this affect the pattern of release of LH and FSH?
- GnRH from hypothalamus determines the release of LH and FSH
- GnRH release is pulsatile and therefore LH and FSH are also pulsatile
