Male Reproductive Endocrinology

T/F - Male reproductive function continue from puberty until death.

true - although at a diminished rate as one ages.

Production of sperm can continue throughout the adult life of a male. Contrast this with the quite different phenomenon in the x.

Production of sperm can continue throughout the adult life of a male. Contrast this with the quite different phenomenon in the female.

*****Endocrine control of male reproductive functions A. Testosterone, LH and FSH are the key players 1. GnRH from hypothalamus determines the release of x and x 2. x release is pulsatile and therefore LH and FSH are also pulsatile 3. x is produced in testes under stimulus of LH B. Control of spermatogenesis 1. x of spermatogenesis (and repackaging) requires presence of FSH 2. x of spermatogenesis requires testosterone 3. x receptors are found only on Sertoli cells. Responses to FSH include the following: a. Stimulation of x, activation of the usual cascade of events that lead to x 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 x of testicular fluid c. x can now proceed to completion (if testosterone is present) d. x level is affected by negative feedback of inhibin acting on the pituitary C. Control of testosterone secretion 1. Production of testosterone is dependent on the presence of LH 2. Leydig cells have x receptors and respond to LH by: (FIG. 16) a. Increasing production of x 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 x and pituitary release of x c. x produced in the Leydig cells also diffuses directly to neighboring Sertoli cells producing paracrine effects such as promoting the production of ABP

*****Endocrine control of male reproductive functions A. Testosterone, LH and FSH are the key players 1. GnRH from hypothalamus determines the release of LH and FSH 2. GnRH release is pulsatile and therefore LH and FSH are also pulsatile 3. Testosterone is produced in testes under stimulus of LH B. Control of spermatogenesis 1. Initiation of spermatogenesis (and repackaging) requires presence of FSH 2. Maintenance of spermatogenesis requires testosterone 3. 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 C. Control of testosterone secretion 1. Production of testosterone is dependent on the presence of LH 2. Leydig cells have LH receptors and respond to LH by: (FIG. 16) 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 c. Testosterone produced in the Leydig cells also diffuses directly to neighboring Sertoli cells producing paracrine effects such as promoting the production of ABP

*****Endocrine control of male reproductive functions A. Testosterone, LH and FSH are the key players 1. x from hypothalamus determines the release of LH and FSH 2. GnRH release is xle and therefore LH and FSH are also xle 3. Testosterone is produced in testes under stimulus of x B. Control of spermatogenesis 1. Initiation of spermatogenesis (and repackaging) requires presence of x 2. Maintenance of spermatogenesis requires x 3. FSH receptors are found only on x cells. Responses to FSH include the following: a. x of cAMP, activation of the usual cascade of events that lead to increased protein synthesis (including synthesis of x-binding protein—ABP) b. This increased metabolic activity leads to x of the Sertoli cell and an x in secretion of testicular fluid c. Spermatogenesis can now proceed to completion (if x is present) d. FSH level is affected by negative feedback of inhibin acting on the x C. Control of testosterone secretion 1. Production of testosterone is dependent on the presence of x 2. x cells have LH receptors and respond to LH by: (FIG. 16) a. Increasing production of cAMP followed by increased testosterone production within x-x minutes b. The testosterone that is released diffuses into the circulation and results in x feedback on hypothalamic release of GnRH and pituitary release of LH c. Testosterone produced in the Leydig cells also diffuses directly to neighboring Sertoli cells producing paracrine effects such as promoting the production of x.

*****Endocrine control of male reproductive functions A. Testosterone, LH and FSH are the key players 1. GnRH from hypothalamus determines the release of LH and FSH 2. GnRH release is pulsatile and therefore LH and FSH are also pulsatile 3. Testosterone is produced in testes under stimulus of LH B. Control of spermatogenesis 1. Initiation of spermatogenesis (and repackaging) requires presence of FSH 2. Maintenance of spermatogenesis requires testosterone 3. 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 C. Control of testosterone secretion 1. Production of testosterone is dependent on the presence of LH 2. Leydig cells have LH receptors and respond to LH by: (FIG. 16) 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 c. Testosterone produced in the Leydig cells also diffuses directly to neighboring Sertoli cells producing paracrine effects such as promoting the production of ABP

3 major stages of sperm maturation and prep before fertilization

1. Maturation - sperm acquire motility passing through epididymis 2. Capacitation in female reproductive tract - motility increases even more and lipo/glycoproteins removed from head of sperm 3. Activation in oviduct near ovum (acrosome rxn takes place and sperm become hypermotilie.

A. Spermatogenesis (FIG. 2) 1. x produces primary spermatocytes (diploid cells) 2. Two successive stages of x result in sperm (x cells)

A. Spermatogenesis (FIG. 2) 1. Mitosis produces primary spermatocytes (diploid cells) 2. Two successive stages of meiosis result in sperm (haploid cells)

***Actions of FSH and LH on the cells of the testis. NOTE: x stimulates Leydig cells to produce testosterone (T), while x stimulates Sertoli cells to produce androgen- binding protein (ABP) and stimulates spermatogenesis. The released testosterone diffuses directly to Sertoli cells (xcrine effect) and diffuses into the circulation for distribution throughout the body. Spermatogenesis requires a high concentration of testosterone in the seminiferous tubule which is made possible by x.

Actions of FSH and LH on the cells of the testis. NOTE: LH stimulates Leydig cells to produce testosterone (T), while FSH stimulates Sertoli cells to produce androgen- binding protein (ABP) and stimulates spermatogenesis. The released testosterone diffuses directly to Sertoli cells (paracrine effect) and diffuses into the circulation for distribution throughout the body. Spermatogenesis requires a high concentration of testosterone in the seminiferous tubule which is made possible by ABP.

Actions of FSH and LH on the cells of the testis. NOTE: LH stimulates x cells to produce testosterone (T), while FSH stimulates x cells to produce androgen- binding protein (ABP) and stimulates spermatogenesis. The released testosterone diffuses directly to Sertoli cells (paracrine effect) and diffuses into the circulation for distribution throughout the body. Spermatogenesis requires a high concentration of testosterone in the x which is made possible by ABP.

Actions of FSH and LH on the cells of the testis. NOTE: LH stimulates Leydig cells to produce testosterone (T), while FSH stimulates Sertoli cells to produce androgen- binding protein (ABP) and stimulates spermatogenesis. The released testosterone diffuses directly to Sertoli cells (paracrine effect) and diffuses into the circulation for distribution throughout the body. Spermatogenesis requires a high concentration of testosterone in the seminiferous tubule which is made possible by ABP.

Actions of FSH and LH on the cells of the testis. NOTE: LH stimulates Leydig cells to produce x, while FSH stimulates Sertoli cells to produce x and stimulates x. The released testosterone diffuses directly to x cells (paracrine effect) and diffuses into the circulation for distribution throughout the body. Spermatogenesis requires a high concentration of x in the seminiferous tubule which is made possible by ABP.

Actions of FSH and LH on the cells of the testis. NOTE: LH stimulates Leydig cells to produce testosterone (T), while FSH stimulates Sertoli cells to produce androgen- binding protein (ABP) and stimulates spermatogenesis. The released testosterone diffuses directly to Sertoli cells (paracrine effect) and diffuses into the circulation for distribution throughout the body. Spermatogenesis requires a high concentration of testosterone in the seminiferous tubule which is made possible by ABP.

Cell division during spermatogenesis. NOTE: mitosis yields primary spermatocytes each with a full complement of chromosomes (#). Meiosis then generates spermatids and then spermatozoa ("sperm") with a haploid number of chromosomes (#).

Cell division during spermatogenesis. NOTE: mitosis yields primary spermatocytes each with a full complement of chromosomes (46). Meiosis then generates spermatids and then spermatozoa ("sperm") with a haploid number of chromosomes (23).

Development of sperm fertility (FIG. 6) Following spermatogenesis, the sperm that enter the head of the epididymis lack x and are not yet capable of fertilizing an egg. Sperm must undergo a series of transformation to successfully enter an egg and fertilize it. 1. Maturation (in x) a. Sperm begin to acquire motility as they pass from the rete testis through the x and epididymis to the vas deferens b. Acquisition of motility is dependent on the intracellular pH going up/down? and x entering the sperm c. Other changes occur to x morphology d. Maturational changes dependent on androgens (with a possible role for x which is also produced in the male) 2. Capacitation (in x tract) a. Occurs in the female reproductive tract b. May result from something found in the x-primed female reproductive tract c. More likely to involve removal of glycoprotein "x factor"(acquired in the x) from the outer membrane of the x of sperm d. Motility increases still more as x channels in the sperm membrane open and result in an additional xward movement of H+ ions (pH inside sperm x further) 3. Activation (near the egg) a. Occurs in x b. Sperm become xmotile c. This is dependent on x entering the sperm and x leaving d. Surface membrane of the sperm fuses with the xsomal 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 x to one that moves the sperm forward along the oviduct to the egg

Development of sperm fertility (FIG. 6) Following spermatogenesis, the sperm that enter the head of the epididymis lack motility and are not yet capable of fertilizing an egg. Sperm must undergo a series of transformation to successfully enter an egg and fertilize it. 1. 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) 2. 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 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) 3. Activation (near the egg) a. Occurs in oviduct b. Sperm become hypermotile b. This is dependent on Ca2+ entering the sperm and H+ leaving c. Surface membrane of the sperm fuses with the acrosomal membrane (the acrosome reaction) d. Membrane over the middle and posterior half of sperm head becomes capable of fusing with the egg membrane e. Motile activity of sperm changes pattern to one that moves the sperm forward along the oviduct to the egg

Functional anatomy of the male (FIG. 1) A. Penis (conveys male gametes to female gametes) 1. prepuce 2. glans 3. corpora cavernosa 4. corpus spongiosum 5. X ligament of penis B. Prostate gland (secretes an X fluid to neutralize the X conditions in vagina) C. Seminal X D. X's gland (bulbourethral) E. Vas deferens (carries sperm to the penis) F. Testicles 1. X tubules (site of spermatogenesis) 2. X (carries sperm from the testes)

Functional anatomy of the male (FIG. 1) A. Penis (conveys male gametes to female gametes) 1. prepuce 2. glans 3. corpora cavernosa 4. corpus spongiosum 5. suspensory ligament of penis B. Prostate gland (secretes an alkaline fluid to neutralize the acidic conditions in vagina) C. Seminal vesicle D. Cowper's gland (bulbourethral) E. Vas deferens (carries sperm to the penis) F. Testicles 1. seminiferous tubules (site of spermatogenesis) 2. epididymis (carries sperm from the testes)

*Gonadotropin regulation in males (FIG. 11) 1. There are no X feedback mechanisms in the male (although there are in the female, as we will see later) 2. Negative feedback by X on LH release from anterior pituitary a. x, but not x, of LH pulses is decreased by testosterone b. Since frequency of LH pulses is directly determined by x of GnRH pulses, this suggests that the negative feedback is on the hypothalamus (the source of GnRH). c. T/F- There are a large number of testosterone receptors on cells in pituitary, suggesting that feedback also occurs onto pituitary 3. The negative feedback of testosterone on FSH secretion from anterior pituitary is stronger/weaker? than the inhibition of LH 4. FSH secretion is strongly inhibited by x from x cells a. Effect is at level of x since GnRH levels are unchanged

Gonadotropin regulation in males (FIG. 11) 1. There are no positive feedback mechanisms in the male (although there are in the female, as we will see later) 2. 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 3. The negative feedback of testosterone on FSH secretion from anterior pituitary is weaker than the inhibition of LH 4. FSH secretion is strongly inhibited by inhibin (from Sertoli cells) a. Effect is at level of pituitary since GnRH levels are unchanged

Gonadotropin regulation in males (FIG. 11) 1. T/F- There are no positive feedback mechanisms in the male. 2. Negative feedback by testosterone on X release from anterior pituitary a. Frequency, but not amplitude, of LH pulses is X by testosterone b. Since X of LH pulses is directly determined by X of GnRH pulses, this suggests that the negative feedback is on the hypothalamus (the source of GnRH). c. There are a large number of X receptors on cells in pituitary, suggesting that feedback also occurs onto pituitary 3. The negative feedback of testosterone o nX secretion from anterior pituitary is weaker than the inhibition of LH 4. X secretion is strongly inhibited by inhibin (from Sertoli cells) a. Effect is at level of pituitary since X levels are unchanged

Gonadotropin regulation in males (FIG. 11) 1. There are no positive feedback mechanisms in the male (although there are in the female, as we will see later) 2. 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 3. The negative feedback of testosterone on FSH secretion from anterior pituitary is weaker than the inhibition of LH 4. FSH secretion is strongly inhibited by inhibin (from Sertoli cells) a. Effect is at level of pituitary since GnRH levels are unchanged

LH secretion is pulsatile with a period of approximately X hours. This is due to pulsatile release of x from the hypothalamus with the same period. Negative feedback of x on the hypothalamus decreases the frequency of GnRH pulses (increases the interval between pulses).

LH secretion is pulsatile with a period of approximately 2 hours. This is due to pulsatile release of GnRH from the hypothalamus with the same period. Negative feedback of testosterone on the hypothalamus decreases the frequency of GnRH pulses (increases the interval between pulses).

x secretion is pulsatile with a period of approximately 2 hours. This is due to pulsatile release of GnRH from the hypothalamus with the same period. Negative feedback of testosterone on the hypothalamus decreases the frequency of x pulses (increases the interval between pulses).

LH secretion is pulsatile with a period of approximately 2 hours. This is due to pulsatile release of GnRH from the hypothalamus with the same period. Negative feedback of testosterone on the hypothalamus decreases the frequency of GnRH pulses (increases the interval between pulses).

Morphology and function of sperm (FIG. 5) 1. Head contains the genetic material 2. The x piece contains mitochondria which provide the x to power the motility produced by the "tail" of the sperm

Morphology and function of sperm (FIG. 5) 1. Head contains the genetic material 2. The middle piece contains mitochondria which provide the ATP to power the motility produced by the "tail" of the sperm

Production of sperm in the testes (FIG. 4) 1. Seminiferous tubules are bounded by a wall made up of x tissue and an epithelium 2. x cells inside the seminiferous tubule produce sperm 3. x cells immediately outside the tubule produce testosterone

Production of sperm in the testes (FIG. 4) 1. Seminiferous tubules are bounded by a wall made up of connective tissue and an epithelium 2. Sertoli cells inside the seminiferous tubule produce sperm 3. Leydig cells immediately outside the tubule produce testosterone

Testosterone secretion A. Production (FIG. 7 & 8) 1. Biosynthesis - two "parallel" pathways to get to testosterone from cholesterol (the precursor) 2. T/F- Production of androgens in adrenal cortex is the primary source of testosterone. 3. Production of androgens (testosterone) in x provides major source 4. Two other biological active androgens (DHT and 5α androstanediol) are produced in peripheral tissues from x (FIG. 9) 5. 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. B. Systemic effects of testosterone (FIG. 10) 1. Specifically reproductive a. Before birth b. Following birth c. Miscellaneous 2. On secondary sex characteristics a. Non-reproductive effects

Testosterone secretion A. Production (FIG. 7 & 8) 1. Biosynthesis - two "parallel" pathways to get to testosterone from cholesterol (the precursor) 2. Production of androgens in adrenal cortex of minimal importance 3. Production of androgens (testosterone) in testes provides major source 4. Two other biological active androgens (DHT and 5α androstanediol) are produced in peripheral tissues from testosterone (FIG. 9) 5. 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. B. Systemic effects of testosterone (FIG. 10) 1. Specifically reproductive a. Before birth b. Following birth c. Miscellaneous 2. On secondary sex characteristics a. Non-reproductive effects

The hypothalamic-pituitary-gonadal axis controlling male reproductive functions. NOTE: negative feedback of testosterone on x release is more powerful than its feedback on x release. x acts on anterior pituitary to reduce FSH release (but it has a negligible effect on LH).

The hypothalamic-pituitary-gonadal axis controlling male reproductive functions. NOTE: negative feedback of testosterone on LH release is more powerful than its feedback on FSH release. Inhibin acts on anterior pituitary to reduce FSH release (but it has a negligible effect on LH).

The hypothalamic-pituitary-gonadal axis controlling male reproductive functions. NOTE: negative feedback of x on LH release is more powerful than its feedback on FSH release. Inhibin acts on anterior pituitary to x FSH release (but it has a negligible effect on LH).

The hypothalamic-pituitary-gonadal axis controlling male reproductive functions. NOTE: negative feedback of testosterone on LH release is more powerful than its feedback on FSH release. Inhibin acts on anterior pituitary to reduce FSH release (but it has a negligible effect on LH).

The hypothalamic-pituitary-gonadal axis controlling male reproductive functions. NOTE: x feedback of testosterone on LH release is more powerful than its feedback on FSH release. Inhibin acts on anterior pituitary to reduce FSH release (but it has a negligible effect on x).

The hypothalamic-pituitary-gonadal axis controlling male reproductive functions. NOTE: negative feedback of testosterone on LH release is more powerful than its feedback on FSH release. Inhibin acts on anterior pituitary to reduce FSH release (but it has a negligible effect on LH).

The major androgen products of the adrenal cortex are x and x which are weak androgens but are converted to testosterone in peripheral tissues. The amount of testosterone produced in the adrenals is insignificant. NOTE: The x are the physiologically important source of testosterone.

The major product of the adrenal cortex are DHEA and androstenedione which are weak androgens but are converted to testosterone in peripheral tissues. The amount of testosterone produced in the adrenals is insignificant. NOTE: The testes are the physiologically important source of testosterone.