The primary hormone produced by the testes is testosterone, a steroid hormone important in the development of the testicular reproductive system, the maturation of sperm cells, and the development of secondary sex characteristics such as a deepened voice, body hair, and increased muscle mass. Interestingly, testosterone is also produced in the ovaries, but at a much-reduced level.
Testosterone, an androgen, is produced by Leydig cells. The alternate term for Leydig cells, interstitial cells, reflects their location between the seminiferous tubules in the testes. In male embryos, testosterone is secreted by Leydig cells by the seventh week of development, with peak concentrations reached in the second trimester. This early release of testosterone results in the anatomical differentiation of the male sexual organs. In childhood, testosterone concentrations are low. They increase during puberty, activating characteristic physical changes and initiating spermatogenesis.
IN CONTEXT
Everyday Connection: Anabolic Steroids
Commonly used for performance enhancement, anabolic steroids are synthetic versions of the sex hormone testosterone. By boosting natural levels of this hormone, athletes experience increased muscle mass. Synthetic versions of human growth hormones are also used to build muscle mass.
A Bodybuilder Preparing to Inject Anabolic Steroids
The use of performance-enhancing drugs is banned by all major collegiate and professional sports organizations in the United States because they impart an unfair advantage to athletes who take them.
In addition, the drugs can cause significant and dangerous side effects. For example, anabolic steroid use can increase cholesterol levels, raise blood pressure, and damage the liver. Altered testosterone levels (both too low or too high) have been implicated in causing structural damage to the heart and increasing the risk for cardiac arrhythmias, heart attacks, congestive heart failure, and sudden death.
Paradoxically, steroids can have effects such as shriveled testicles and enlarged breast tissue. In females, their use can cause effects such as an enlarged clitoris and growth of facial hair. In all people, their use can promote increased aggression (commonly known as “roid-rage”), depression, sleep disturbances, severe acne, and infertility.
term to know
Leydig Cells
Cells between the seminiferous tubules of the testes that produce testosterone; a type of interstitial cell.
1a. Functions of Testosterone
The continued presence of testosterone is necessary to keep the male reproductive system working properly, and Leydig cells produce approximately 6 to 7 mg of testosterone per day. Testicular steroidogenesis (the manufacture of androgens, including testosterone) results in testosterone concentrations that are 100 times higher in the testes than in the circulation. Maintaining these normal concentrations of testosterone promotes spermatogenesis, whereas low levels of testosterone can lead to infertility.
In addition to intratesticular secretion, testosterone is also released into the systemic circulation and plays an important role in muscle development, bone growth, the development of secondary sex characteristics, and maintaining libido (sex drive) in both males and females. In females, the ovaries secrete small amounts of testosterone, although most is converted to estradiol. A small amount of testosterone is also secreted by the adrenal glands in both sexes.
2. Control of Testosterone Production
The regulation of testosterone concentrations throughout the body is critical for male reproductive function. The intricate interplay between the endocrine system and the reproductive system is shown in the image below.
Regulation of Testosterone Production - The hypothalamus and pituitary gland regulate the production of testosterone and the cells that assist in spermatogenesis. GnRH activates the anterior pituitary to produce LH and FSH, which in turn stimulate Leydig cells and Sertoli cells, respectively. The system is a negative feedback loop because the end products of the pathway, testosterone and inhibin, interact with the activity of GnRH to inhibit their own production.
The regulation of Leydig cell production of testosterone begins outside of the testes. The hypothalamus and the pituitary gland in the brain integrate external and internal signals to control testosterone synthesis and secretion. The regulation begins in the hypothalamus. The pulsatile release of gonadotropin-releasing hormone (GnRH) from the hypothalamus stimulates the endocrine release of hormones from the pituitary gland. The binding of GnRH to its receptors on the anterior pituitary gland stimulates the release of the two gonadotropins: luteinizing hormone (LH) and follicle-stimulating hormone (FSH). These two hormones are critical for reproductive function in all humans.
In the testes, FSH predominantly binds to the Sertoli cells within the seminiferous tubules to promote spermatogenesis. FSH also stimulates the Sertoli cells to produce hormones called inhibins, which function to inhibit FSH release from the pituitary, thus reducing testosterone secretion. These polypeptide hormones correlate directly with Sertoli cell function and sperm number; inhibin B can be used as a marker of spermatogenic activity. In addition, FSH stimulates the Sertoli cells to secrete androgen-binding proteins (ABP), which bind to testosterone and keep the concentration of testosterone within the testis at high levels. LH binds to receptors on Leydig cells in the testes and upregulates the production of testosterone.
A negative feedback loop predominantly controls the synthesis and secretion of both FSH and LH. Low blood concentrations of testosterone stimulate the hypothalamic release of GnRH. GnRH then stimulates the anterior pituitary to secrete LH into the bloodstream. In the testis, LH binds to LH receptors on Leydig cells and stimulates the release of testosterone. When concentrations of testosterone in the blood reach a critical threshold, testosterone itself will bind to androgen receptors on both the hypothalamus and the anterior pituitary, inhibiting the synthesis and secretion of GnRH and LH, respectively. When the blood concentrations of testosterone once again decline, testosterone no longer interacts with the receptors to the same degree, and GnRH and LH are once again secreted, stimulating more testosterone production. This same process occurs with FSH and inhibin to control spermatogenesis.
3. Andropause
As adult males age, testosterone levels gradually decline and deficiency gradually increases. Declines in Leydig cell activity can occur in males beginning at 40 to 50 years of age. The resulting reduction in circulating testosterone concentrations can lead to symptoms of andropause, also known as male menopause. While the reduction in sex steroids is akin to female menopause, there is no clear sign—such as a lack of a menstrual period—to denote the initiation of andropause. Instead, people with this condition report feelings of fatigue, reduced muscle mass, depression, anxiety, irritability, loss of libido, and insomnia. A reduction in spermatogenesis resulting in lowered fertility is also reported, and sexual dysfunction can also be associated with andropausal symptoms.
Testosterone Levels - Males experience decreased testosterone levels and increased testosterone deficiency as they age.
Whereas some researchers believe that certain aspects of andropause are difficult to tease apart from aging in general, testosterone replacement is sometimes prescribed to alleviate some symptoms. Recent studies have shown a benefit from androgen replacement therapy on the new onset of depression in elderly males; however, other studies caution against testosterone replacement for long-term treatment of andropause symptoms, showing that high doses can sharply increase the risk of both heart disease and prostate cancer.
term to know
Andropause
Comparable to female menopause; a time of decreased production of testosterone, atrophy of interstitial cells, and lessened sexual activity.
summary
In this lesson, you learned about how hormones affect male reproductive capacity and how their production is controlled. First, you explored the importance of testosterone, the most important androgen in males, and the functions of testosterone in human reproduction. You then examined how a negative feedback loop results in the control of testosterone production by other hormones. Finally, you explored andropause, which is the male equivalent of menopause and occurs when testosterone levels gradually decline and deficiency gradually increases.
Terms to Know
Andropause
Comparable to female menopause; a time of decreased production of testosterone, atrophy of interstitial cells, and lessened sexual activity.
Leydig Cells
Cells between the seminiferous tubules of the testes that produce testosterone; a type of interstitial cell.
