Male reproductive physiology

Male Reproductive Physiology
January 23, 2004

In mammals, the reproductive hormones are more for a preservation of species, not
preservation of an individual.
In this lecture, we will consider the following definitions of sex: Chromosomal sex is the
chromosomal configuration (XX or XY) of an individual; Gonadal sex is whether or not
the gonads are testis or ovaries; Phenotypic sex is whether an individual is a boy or girl.
Development of the Male Reproductive System—The testes are the male reproductive
organs that are responsible for two main functions: the production of testosterone and the
production of sperm.
During fetal development, the gonads begin to differentiate from indifferent gonadal
tissue. In the male, there is a SRY gene present on the Y chromosome. It is responsible
for the release of an SRY antigen which stimulates the development of the indifferent
gonadal tissue into the testis.
The testis have two distinct cell types. The Sertoli cells are found within the
seminiferous tubules of the developing testis. They produce Mullerian inhibiting
substance/hormone (MIS or MIH) which causes the Mullerian ducts to regress. The
Mullerian duct is the gonadal tissue that will develop into a uterus, uterine tubes, and the
upper part of the vagina in females. The Leydig cells (AKA interstitial cells) are found
outside of the developing seminiferous tubules. They produce testosterone which
promotes the transformation of the Wolffian ducts into the epididymis, vas deferens, and
seminal vesicles. Testosterone is also converted into dihydrotestosterone (DHT) in
certain tissues by the enzyme 5-α-reductase. DHT is responsible for the development of
the external male genitalia. If an individual is deficient in 5-α-reductase, this can lead to
ambiguous external genitalia. This type of condition is seen in males in the Dominican
Republic. They are raised as females, but during puberty, there is heavy gonadotropin
influence which can lead to the development to male external genitalia.
Testicular Descent—The testis are formed within the male abdominal cavity. However,
this is not a favorable environment for spermatogenesis to occur because the core body
temperature is too high for this process to occur. The testis will descend to the scrotal sac
outside of the body. First there will be trans-abdominal movement of the testis. Then,
each one will descend through the inguinal canal to reach the scrotal sac. The
development and descent of the testis takes the entire gestational period.
In some males, the testis has not fully descended at birth on one or both sides. This
condition is called cryptorchidism. It may be due to mechanical problems, such as the
inguinal canal closing prematurely. This must be corrected by surgery. It may also be
due to some form of hormonal deficiency. In either case, the descent of the testis is
recommended, because an abnormal testicular location is a source of malignancy and also
creates infertility problems.
The temperature within the scrotal sac is maintained by the cremasteric muscle. This
muscle can contract or relax to raise the testis in response to the environmental
temperature. The pampiniform venous plexus is also involved in the regulation of
temperature of the testis. If there is an increase in temperature of the testis (for example,
due to febrile infection or extremely hot environmental conditions), sperm production can
be inhibited/shut off.
Cells of the Testis—The testis contains spermatogonia and Sertoli cells within the
seminiferous tubules and Leydig cells (interstitial cells) on the periphery. The
spermatogonia are the stem cells within the seminiferous tubules. They create a
spermatogenic wave; that is, there is a continual production of mature sperm. This
process takes 60-70 days. The Sertoli cells are the source of Mullerian Inhibiting
Substance. This controls testicular descent and Mullerian duct degeneration in males.
The Sertoli cells provide a structural attachment for normal seminiferous tubule
production. They also are responsible for the nourishment of the spermatogonia. The
Leydig cells produce testosterone. It has many effects on the reproductive system and
throughout the body and will be described below.
Sertoli Cell Functions—The Sertoli cells form the blood-testis barrier. The Sertoli
cells are joined by gap junctions. These barriers separate the spermatogonia from the
spermatocytes. It also protects the developing cells from potentially toxic circulating
elements in the blood and also prevents the developing cells from entering the circulation
and causing autoimmune destruction of the testis. Steroids such as testosterone can enter
through this barrier. This is important b/c the completion of spermatogenesis requires
testosterone.
The Sertoli cells also secrete androgen binding protein (ABP). ABP is responsible for
bringing in testosterone and maintaining it in a high concentration on the luminal side of
the tubules. This is necessary for sperm maturation, the completion of spermatogenesis.
The Sertoli cells produce aromatase-E2, an enzyme that converts androgens to estrogen.
Tumors of the Sertoli cell are often associated with high levels of estrogen. This causes
feminization b/c of the high levels.
Sertoli cells produce a watery bicarbonate secretion. This secretion contains steroid
hormones, potassium, and amino acids and produces an osmotic gradient that aids in the
transport of spermatids to the epididymis where final maturation occurs.
The Sertoli cells also possess FSH and androgen receptors. The binding of FSH and
androgens to these receptors is responsible for the stimulation of spermiogenesis.
The Sertoli cells also function in the regulation of seminiferous tubule metabolism
and provides nourishment for the developing sperm. They also produce growth
factors for the Leydig cells.
Finally, the Sertoli cells secrete Inhibin and Mullerian Inhibiting Substance. Inhibin
is a protein that inhibits FSH production. The function of MIS is described above.
Hormonal Regulation of the Testis—The hypothalamus releases Gonadatrophin
releasing hormone (GnRH) in a pulsatile manner. GnRH is sent to the anterior pituitary
where it stimulates the pulsatile release of gonadotropins, FSH and LH.

FSH targets the Sertoli cells and binds to specific cell surface receptors here. It initiates
spermatogenesis and also stimulates the Sertoli cell to produce inhibin. The inhibin
protein feeds back on the anterior pituitary to regulate FSH production there.
LH targets the Leydig cells to produce testosterone. It interacts with cell surface
receptors on the Leydig cells to stimulate the production of cAMP. This in turn,
stimulates the secretion of testosterone. Testosterone initiates a response in the
reproductive tract and other body organs. It also travels to the Sertoli cells to promote the
completion of spermatogenesis. Finally, testosterone feeds back on the anterior pituitary
to control LH secretion and on the hypothalamus to inhibit GnRH release.
Testosterone and Transcriptional control—Testosterone binds to receptors within the
nucleus of the Sertoli cells to initiate transcriptional activity. It shares the same nuclear
receptor with DHT, but DHT has a greater affinity for the receptor and elicits greater
transcriptional activity. Within the Sertoli cell, testosterone is converted to estradiol via
aromatase activity. The estradiol then exits the cell and travels to enter the Leydig cell
where it binds to a nuclear receptor to control transcriptional activity here. (this is not
something I really understand, so check this out with someone else if this doesn’t sound
legitimate).
Testosterone Secretion—Testosterone is secreted by the interstitial cells daily. About
98% is bound to protein and 2% is free. Of the bound testosterone, it is either bound to
sex hormone binding globulin or albumin.
The amount of plasma testosterone is high during fetal development and then lowers until
puberty. At puberty, the level begins increasing again until it levels off in adulthood. By
the time a man is older, the levels of plasma testosterone begin to decrease again.
The main source of estrogen in males is its peripheral conversion from androgen in
adipose tissue. It is thought that as a man ages, the amount of adipose tissue increases.
This gives a tendency toward feminization because there is an enhanced production of
estrogen.
Testosterone Effects—Testosterone has both androgenic and anabolic effects. The
androgenic effects are seen on the reproductive tract and accessory structures. These
effects include:
Development of external genitalia and accessory glands Development of pubic, axillary, and body hair Enlargement of the larynx and thickening of the vocal cords Loss of hair in the temporal region of the scalp Sperm production Increased libido and potency Growth of facial hair
The anabolic effects are general growth-promoting effects. These include:
Pubertal growth spurt and stoppage of growth Increased muscle mass (esp. in upper torso) Positive nitrogen and electrolyte balance (especially enhances sodium and water retention) Increased RBC production (leads to a tendency of polycythemia, excessive RBC production) Enlargement of renal and salivary glands
Male sex accessory glands—The epididymis is the primary site of storage and final
maturation of sperm. The vas deferens is the tube which carries the sperm from the
epididymis to the prostate. The seminal vesicles are responsible for the secretion of
about 60& of the semen concentration. They produce prostoglandins which stimulate
uterine contractions and enhance sperm motility and penetration of the cervical mucus.
The seminal vesicles also produce fructose. It serves as an energy source for the sperm
during their transport through the female reproductive tract. The prostate gland secretes
about 30% of the total semen concentration. Its secretion is alkaline which aids in
neutralizing the acidic female reproductive tract. These secretions also contain a clotting
enzyme. The bulbourethral gland also produces an alkaline mucus secretion that serves
to neutralize the male urethra prior to ejaculation.
The prostate enlarges with aging and can cause compression of the urethra and problems
with urinary retention. The secretions of the prostate are testosterone dependent, so it is
thought that by treating an enlarged prostate with a drug (ex. Proscar) that decreases DHT
levels, the amount of prostate hypertrophy can be decreased.
Male Sexual Response—The first phase is the excitatory phase. It involves
parasympathetic stimulation resulting in vasodilation within the erectile tissue in the
penis. This causes an erection, which is associated with the release of nitric oxide. Nitric
oxide relaxes the smooth muscle of the arteries. The next phase is the ejaculatory phase.
This is stimulated by the sympathetic nervous system. In this phase, there is contraction
of the accessory sex glands to release semen into the posterior part of the urethra. There
is then ejaculation of the semen caused by spasmodic contractions of the erectile tissue of
the penis.
Erectile dysfunction is a common problem faced by men. One treatment for this is
Viagra. As mentioned above, nitric oxide is released during an erection. Nitric oxide
stimulates the formation of cGMP. cGMP causes the relaxation of smooth muscle of the
arteries, thereby causing the erection. cGMP is broken down by 5-phosphodiesterase.
Viagra is a phosphodiesterase inhibitor. It blocks the enzyme and allows cGMP to
remain in higher concentrations so the erection can be maintained for longer periods.
Fertility Control in Males—Currently there is no male oral contraceptive. Males can be
sterilized by a procedure called a vasectomy. A vasectomy involves bilateral ligation of
the vas deferens. This procedure can be reversed, but there is a low successive of fertility
following this procedure.
Pathology associated with the Male Reproductive System—Hypogonadism is the
failure of the testis to develop or properly function. One such syndrome is Klinefelter’s
syndrome. It is associated with an XXY chromosomal pattern. These individuals are
tall, sterile, and often have breast enlargement. Another example of hypogonadism is
Kallman’s Syndrome. This is due to a defect in the secretion of pituitary gonadotropins.
Androgen Insensitivity is a disorder in which there is an insensitivity of the target
organs to androgens. This leads to feminization in males and was once called testicular
feminization.

Source: http://www.uams.edu/m2008/notes/phys/pdf/Jan%2023%20Male%20Repro%20Phys.pdf