Androgens are steroid hormones that are responsible for the male principle: the growth and functioning of the male reproductive system, the maintenance of normal sperm levels and the distinctive male features in appearance.
Testosterone secretion and its regulation
Where does testosterone come from?
The main source of testosterone in the body are the testicles. This body produces testosterone directly (5-12 mg / day) and a small amount of dehydroepiandrosterone (DHA), androstenedione and estrogens.
Although all testicular tissues are capable of producing testosterone, the main producer is Leydig cells. The tubular epithelium of the testicle and the adrenal glands are also capable of producing this hormone. They produce DHA, which is transformed into testosterone through a chain of reactions. But this share makes a very small contribution to the main pool of androgens (for more, see “The role of adrenal androgens in the male body” ).
Any hormone, any enzyme and secret is synthesized from a certain substance that enters our body with food. The basis of testosterone is cholesterol. Leydig cells take cholesterol from the blood as acetate or low-density lipoprotein. There is a certain sequence of reactions with the transformation of substances: cholesterol → pregnenolone → 17-hydroxypregnenolone → androstenediol. After passing through chemical reactions, 2 androstenediol molecules are interconnected and the final product → testosterone is released.
The normal constant content of the hormone in the blood is controlled by the hypothalamic-pituitary system . It works on the principle of negative feedback. The hypothalamus produces gonadotropin-releasing hormone, which, in turn, controls the constant secretion of the pituitary gonadotropins (follicle-stimulating and luteinizing hormones).
Luteinizing hormone (LH) controls the maturation of Leydig cells and their further production of steroid hormones. That is, he plays a major role in the start of testosterone synthesis by the testes. Follicle-stimulating hormone (FSH) monitors the complete maturation of the spermatogenic epithelium and increases affinity for LH (by increasing the number of LH receptors).
The feedback principle is that testicular cells signal the hypothalamus about the amount of hormones produced. The alert is made using receptors similar to testosterone on the hypothalamus. If the hormones are in normal quantities, then the pituitary continues to produce the same amount of gonadotropins as before. If there is more testosterone than needed - less of the latter comes into the blood, if less than needed, correspondingly more.
Testosterone Circadian Rhythms
Testosterone production does not occur around the clock at the same level. The hormone has circadian rhythms (see Figure 2). It is synthesized around the clock in small quantities. The highest doses are released into the blood from 6 to 8 in the morning, when the minimum secretion is observed in the evening hours (from 20 to 22 in the evening).
Fig. 2 - Testosterone circadian and one-year rhythms:
graph 1 - testosterone circadian rhythm versus time of day;
graph 2 - testosterone circadian rhythm versus season.
Testosterone metabolism in the body of a man
Testosterone Forms (Fractions)
Testosterone entering the bloodstream can be in 2 states:
Testosterone in the blood is associated with various proteins. It can bind to sex hormone-binding globulin (GSPS) and albumin. This globulin is related to all sex steroids, so not only testosterone, but also estrogens, estradiols and other sex hormones are susceptible to its contact. The androgen associated with the GSM is in a quantitative ratio of about 57%. It is no longer considered active, but only circulates in the blood.
The remaining 43% of circulating hormone has a biological activity. 40% of active testosterone is bound to albumin, and 3% is in a free unbound form. The connection with albumin, in contrast to globulin, is very weak, and under any influence it may weaken, and testosterone will detach from the protein.
The role of SHBG in the hormonal background
The content of the GSAS is controlled by many factors. It can increase, and then the active hormone becomes even smaller. An increase in SHBG may adversely affect the general condition of the body.
The concentration of SHBG may increase in the blood in various conditions:
- taking glucocorticoids orally or parenterally;
- protein deficiency;
- hypothyroidism ;
Physiologically, GSOS increases with age. Redistribution after 40 years can lead to 2 opposite states:
- Either estrogen will begin to predominate, which will be affected by gynecomastia , female-type obesity (putting off fat on the thighs, legs, and abdomen), and mood changes to more tearful.
- If the body goes the other way, then increasing the concentration of GSPS will ensure the normal content of total testosterone in the blood and long-term maintenance of its level while reducing the quantitative indicators of free testosterone.
3 ways metabolism of testosterone
There are 3 ways of metabolism in relation to biologically active testosterone:
- Enhancement of biological activity - after combining with 5α-reductase, testosterone turns into a more active hormonal unit - dihydrotestosterone (this happens in the prostate gland, skin, epididymis, seminal vesicles);
- Changes in biological activity - under the influence of aromatase, the hormone is converted into estradiol (this occurs in the brain, muscles, adipose tissue, and mammary gland);
- Decrease in biological activity - when testosterone enters the liver, 5β-reductase converts the hormone to inactive 5β-dihydrotestosterone and its derivatives sulfates and glucuronides.
Fig. 3 - Changes in the activity of testosterone as a result of metabolic transformations (the androgenic activity of each steroid is indicated in parentheses; the activity of testosterone is taken as 100).
The half-life of the hormone
The circulation of the hormone is short, and the half-life occurs in 2 stages.
- Stage 1 - proceeds in 20 minutes. During this time, almost the entire amount of active testosterone is utilized from the blood. It is absorbed by tissues, the metabolism of which is carried out using a sex steroid.
- Stage 2 - lasts up to 3 hours. A large amount of the hormone is absorbed by adipose tissue, where a kind of depot of sex hormones is located. The remaining amount of the hormone in the blood is utilized by various metabolites through the kidneys and liver.
Almost half of the secreted testosterone is excreted in the urine by metabolites: androsterone, etiocholanolone. These metabolites are a separate group of 17-ketosteroids. Testosterone is also excreted in the form of inactivated testosterone - glucuronide.
Effects of testosterone
Not in vain testosterone is called "the hormone of kings - the king of hormones." After all, he controls almost all functions in the male body. The hormone can do it directly - directly penetrating into the cell nucleus, or indirectly - controlling the work of other hormones.
Testosterone in the male body performs the main classic functions:
- Androgenic function - testosterone provides a manifestation of the secondary sexual characteristics of men . Due to the high content of testosterone prevailing over estrogen, male-type hair growth occurs (body hair on the face, chest, buttocks and genitals). The growth and development of the male genital gonad and external genital organs, the male type physique (distribution of adipose tissue) is ensured. Baldness and baldness also controls testosterone. Interestingly, body fat is also controlled by testosterone. If women have superficial obesity, due to subcutaneous fatty tissue, in men fat is deposited in the parenchymal organs and on the greater omentum.
- Anabolic function - sex steroid provides the growth of muscle fibers, the necessary density of bone tissue, takes part in the production of the necessary organ-specific proteins in the kidneys, liver, sweat and sebaceous glands.
- Antigonadotropic function - high testosterone inhibits gonadotropins. The general principles of implicit feedback between the gonads and the hypothalamic-pituitary system are followed.
- Reproductive function - without the required amount of testosterone, the formation of sperm cells is impossible. The hormone is the “motor lever” of spermatogenesis. It also provides erectile function and sexual desire.
- Psychophysiological function - due to the male sex steroid stereotypical behavior, some character traits are formed. It is testosterone that provides the necessary libido, increased aggression in behavior, the desire to fight, the attenuation of the feeling of fear. The hormone has a psychostimulant effect.
- Hematopoietic function - indirectly affects hematopoiesis. Testosterone can affect erythropoiesis in the red bone marrow, enhancing it. It also has an effect on the production of erythropoietin in the kidneys. The ratio of erythropoietin to testosterone works on the principle of a direct positive relationship - the more testosterone, the more erythropoietin is produced.
I.I. Dedov, S. Yu. Kalinchenko, “Age androgen Deficiency in Men”, Moscow, 2006.