Testosterone metabolism

The testicle has two basic functions: endocrine (production of hormones) and exocrine (production of sperm). 85-90% of the interior of the testicular volume is made up of seminiferous tubules and their germinal epithelium, the place where sperm are produced (from 10 to 20 million gametes per day), and only 10-15% is occupied by the interstitium, where testosterone is produced.
The adult male testicle produces approximately 5 to 7 mg of testosterone per day. Testosterone secretion is adjusted to a circadian rhythm, with late afternoon minima and late evening and early morning maxima. Variations can reach an amplitude of 36%. This explains the importance of making the analytical determination of this hormone first thing in the morning.
Testosterone is produced from cholesterol in Leydig cells, under the influence of LH. Enzymes break the side chain of cholesterol in these cells to form pregnenolone.
Other enzymes contribute to the development of a series of biosynthetic steps to transform pregnenolone into the definitive testosterone: pregnenolone, progesterone, dihydroepiandrostedione, androstediol and, finally, testosterone.
Pituitary LH stimulates the production of testosterone by Leydig cells located in the interstitium of the testicle, and by fixation to specific receptors existing in the membrane of that cell.
The release of LH is a discontinuous process and occurs, fundamentally, during the night and in a pulsating way, at intervals of about 90 minutes. It corresponds to the pulsatile secretion of GnRH. The available levels of this hormone will determine the amount of testosterone secretion. But in turn, testosterone levels exert a reciprocal effect by inhibiting the production of LH in

the pituitary gland through two mechanisms:

Testosterone has a weak negative feedback effect on the adeno-hypophysis, which results in a decrease in LH secretion.
On the other hand, testosterone directly inhibits the secretion of GnRH in the hypothalamus, causing a decrease in LH gonadotropin in the adeno-hypophysis, which will reduce the production of testosterone in Leydig cells. Most of the inhibition of male hormone secretion is attributed to this feedback mechanism.
Testosterone has a depressing effect on hypothalamic and pituitary function, on the production of gonadotropins (FSH and LH).
Estradiol has depressing effects on hypothalamic and pituitary production.
FSH stimulates the production of several proteins in Sertoli cells, such as inhibin, important for retrocontrol, which slows or suppresses the production of FSH.
Free testosterone diffuses passively over target cells where it can be metabolized to another androgen of greater activity, dihydrotestosterone (5α-DHT) by alpha-reductase, or to estradiol by the action of aromatase.
There are two isoenzymes of 5α-reductase, type I (found in the skin and liver) and type II (found in the prostate, adrenal gland, seminal vesicle, genital skin, hair follicle and cerebral cortex).
Approximately 80% of circulating DHT is produced by the peripheral conversion of free testosterone, and 20% is secreted directly by the testes. both testosterone and DHT are attached to the same androgen receptor and their effects complement each other, but the affinity is much more potent in the case of DHT.
At the sexual level, it plays a fundamental role in the development and maintenance of sexual characteristics and in the development and functioning of the male sex glands. As a hormone of desire, it is known that androgens act on the central nervous system (CNS), stimulating and maintaining desire, sexual motivation.
But to maintain sexual desire requires a dose of testosterone, and many other factors influence. It seems that testosterone is necessary for the normal functioning of the ejaculation mechanism and the maintenance of spontaneous erections.
Its positive influence on erectile response is also known. Testosterone stimulates the activity of an enzyme, nitric oxide synthetase, which helps to maintain adequate levels of nitric oxide (ON) in the smooth muscle of the corpora cavernosa of the penis. On the other hand, it has been shown to promote the activity of phosphodiesterase type 5.

But testosterone and its metabolites are much more than a sex hormone, and play many important physiological actions in the body, are essential for male health.
Androgens play an important role in activating cognitive function; they increase lean body mass; they maintain bone mass (hypogonadism is one of the main causes of osteoporosis in men); they stimulate erythropoiesis.
They also have a clear effect on lipids: it improves the concentration of high-density lipoproteins (HDL) and decreases the concentration of low-density lipids, the so-called “bad cholesterol” (LDL) which promotes cardiovascular health and even an increase in life expectancy.
To understand the male hormonal physiology and to know better the functions of testosterone, in the sexual sphere and in the organism in general, permite・entender the clinical consequences of any alteration in the levels of this hormone.

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