Endocrinology of Male Reproductive System

During the first 5 weeks the fetal gonads are indistinguishable, which means the cells are not committed to either sex yet.. However between the 6-7 week of gestation gametogenesis starts. The SRY gene on the short arm of the Y chromosome is responsible for male phenotype development. This gene codes for TDF (testis determining factor). After testis development, they release two factors that then push on the development of the male reproductive tract, MIF and Testosterone.

MIF- mullerian-inhibiting factor is responsible for stopping the formation of the female reproductive tract. Testosterone- is then responsible for pushing the male reproductive tract to form.

There are two types of cells that responsible for the development of the male reproductive tract Sertoli and Leydig cells.

Sertoli cells

These cells produce MIF or also called AMH (antimullerian hormone) which cause the mullerian ducts to atrophy (mullerian ducts later develop into the fallopian tubes, uterus, and vagina)

Leydig cells

Are the testosterone secreting cells of the testis. Testosterone promotes the wolffian or mesonephric ducts to develop into epididymis, vas deferens, seminal vesicles, and ejaculatory ducts. Testosterone is converted to its active form, dihydrotestosterone, by 5alpha- reductase,

The female tract development is governed by the gene DAX-1 found on the X-chromosome.

For male tract development there are 3 integral pituitary hormones:

LH- goes to Leydig cells and stimulates them to produce testosterone.

FSH- stimulates sertoli cells to start spermatogenesis and start the transport of sperm to the epididymis.

Prolactin- is really only needed in females to produce milk, however in males it can cause them to become desensitized to gonadotropin hormone (GnRH) and cause impotence.

Accessory glands are controlled by testosterone and alpha D testosterone.

In couple’s seeking help for infertility, a physician may perform a post-coital test (PCT), which is a physiological test for:

• Was intercourse really there

• Was there ejaculation

• How many sperm and what quality

• Was there interaction of sperm with nucleus

You may be wondering why such a test is necessary, I mean if a couple is seeking help for infertility, they’re going to be having sex, right? Well guess what, some patients do lie, and a physician needs to know if infertility is really due to lack of coitus.

GnRH is released from hypothalamus, acts on anterior pituitary to release LH and FSH (these hormones are released from same gonadotroph cells). LH acts on Leydig cells and FSH acts on Sertoli cells.

LH causes the release of testosterone in males and estrogen in females

Then FSH and Testosterone together cause spermatogenesis and release of inhibin from sertoli cells.

Inhibin is part of a feedback loop. It acts back on anterior pituitary to discontinue release of FSH. Therefore, if you have a male who has high testosterone and FSH, it is a sign that he is not producing sperm and inhibin.

The frequency and amplitude of GnRH can change ratio of FSH and LH example polycystic ovary or sperm quality. (Can change ratio by pumping in exogenous GnRH to fix the ratio artificially). Obstructive azosperma is caused by obstruction in the vas deferens.

Testis should be 3 degrees below body temperature, because the testis blood barrier is only efficient in hypothermic conditions. The testis are cooled by air circulating around the scrotum. Now blood supply to the testes consists of a network of veins and artery, in which the veins kind of form this meshwork around the artery. This allows the blood to warm up on its way back into the body. Now in some cases a varicocele forms in the veins, this is similar to a varicose vein in leg, where a valve fails and blood pools in the vein causing a bulge. Because there is now blood pooling in the testis, the temperature raises in the testis, causing a decrease in the quality of the sperm. Now this rarely happens on the right side, is more common on the left side, due to the difference in their connection to the inferior vena cava. They can perform a surgery to correct the varicocele, which does increase the quality of the sperm. However, case studies have shown that men who have the surgery and those who do not have the same fertility rates. Therefore it is only necessary to have the corrective surgery for pain or discomfort.

Testis

• Length = 4.5 cm

• Volume~ 20 mL

  • 70% volume seminiferous tubules

  • 30% interstitial tissue

Mesenchymal cells

Leydig cells- proliferation depends on LH

hCG (human chroinic gonadotroph) is governed by LH, hCG causes increase in production of testosterone.

In females, testosterone gets converted to estrodial almost immediately, in males high levels of testosterone will get converted to estrodial. Therefore if there is a problem with the cell receptor for testosterone, and the cells can not take up and metabolize the testosterone. The levels of testosterone will be high, it will get converted to estrodial, and the cells will then take up estrodial and the genetic male will develop female characteristics. Any defect in testosterone receptor will cause inactivation of the receptor.

In the testes you will find Leydig cells surrounding blood vessels and tubules. Leydig cells excrete testosterone into the blood stream for its exocrine action. In tubules, Leydig cells have a paracrine action of testosterone, and the testosterone level is 400 times higher around tubules than in serum.

There are two binding proteins for testosterone:

• SHBG- sex hormone binding globulin- it’s produced by the liver and found in the blood

• ABP- androgen binding protein- found in sertoli cells.

There are two pathways and sites for testosterone production

1. In adrenal (makes 5% of testosterone) Cholesterol is converted to pregnenolone, which is then converted to 17-alpha-hydroxypregnenolone, then to dehydroepiandrosterone, then to Androstenedione, then to Testosterone.

2. In testes, (95% of testosterone) Cholesterol is converted to pregnenolone, which is then converted to progesterone, then to 17-alpha-hydroxyprogesterone, then to androstenedione, then to testosterone

In the formation of testosterone, LH binds to the receptor and causes increase in formation of cholesterol from cholesteryl esters via cAMP, and via PKA causes conversion of cholesterol to pregnenolone.

Action of Testosterone

• Gonadotropin regulation

• Spermatogenesis

• Sexual Differentiation

• Sexual Maturation at Puberty

In circulation, 60% of testosterone is bound to SHBG, 40% is bound by Albumin, and only about 2% is free testosterone (I know the numbers don’t add up but this is what he gave in class). The testosterone avalible to receptor (Bioavailability) is about 40%, the free will be used first and then the testosterone bound to albumin, (it is much harder to get it released from SHBG).

Spermatogenesis

Takes place in the tubules, walls are 3-5 layers of myeloid cells, germ cells develop to sperm cells and are released into the lumen, takes about 3 months.

There are 3 phases

• Proliferation -2n cells

• Meiosis- 4n cells

• Spermatogenesis-1n spermatids

The Sertoli cells are important for spermatogenesis, for endo, para, and genetic control. These cells are controlled by LH and testosterone. The meiosis phase has essential need for testosterone. Therefore, if infertility is thought to be due to low levels of testosterone. You give hCG instead of testosterone. Because hCG stimulates the Leydig cells to release testosterone right next to the Sertoli cells instead of having to go through circulation.

Erection of the penis is under parasympathetic control. It is due to vasodilatation of the arterioles and muscle relaxation. Viagra activates cGMP, the second messenger for vasodilatation.

Ejaculation is under sympathetic control. It is due to the contraction of the vessels in reflex to fluid in the posterior urethra. There are 3 glands involved in ejaculation, seminal vesicle, prostrate, and Cowper ’s gland.

Category: Physiology Notes