Testosterone

Infobox - hormone }}
 * name = Testosterone
 * picture = Testosterone.png
 * prekurzor = cholesterol, progesterone
 * gland = endocrine
 * structure =
 * target organ/tissue =
 * receptor =
 * effects = determines the development of the male phenotype, the growth of the genital organs, the appearance of secondary sex characteristics, stimulates spermatogenesis (in men)
 * OMIM =

Testosterone, the most important agent of androgens, is a steroid hormone produced in men primarily by Leydig cells. One-third produces zona reticularis addrenal (here testosterone is produced not directly, but another androgen with a similar function – dehydroepiandrosterone, short for DHEA).' Testosterone is derived from progesterone, which is produced by gradual modifications of the carbon skeleton cholesterol (dehydrogenation, isomeration, ...).

Brief anatomy of testes
Testicles are a paired ellipsoid-shaped organ with dimensions ranging from 3.6-5.5&thinsp;cm in length and 2.1-3.2&thinsp;cm in width. Their volume is around 18.6&thinsp;ml. They are stored in a scrot that has both a protective package function and an important role in temperature control, which should be 3-4°C lower than the abdominal temperature.'  Testicular cover consists of 3 layers of membranes:  'tunica vaginalis, tunica albuginea and tunica vasculosa. The testes themselves are functionally and morphologically divided into two sections: intersticium' and seed ducts.'. These individually provide two main functions: spermatogenesis and steroidogenesis.

Leydig cells
The endocrine elements of the testicles, Leydig's [cell|buys]], are found in interstic, which occupies approximately 10-15 % of the testicles and fills the area between the seed ducts. The cells themselves are represented here by 20% in number (about 350 million). Together with Leydig cells, intersticium also contains immune system cells (macrophages and lymphocytes] which, by producing cytokine, affect the proliferation, differentiation and endocrine function of steroidogenic cells. Leydig cells are of origin mesenchyme] and were formed by differentiation of fibroblast-like intersticia cells due to luteinizing hormone. These cells are rich in endoplasmic reticulum and mitochondria and at the same time we can find abundant lipid droplets and lipofuscin residues in them. Their main function is testosterone secretion.

Production and transport
Androgens are produced in men from 2/3 testes and 1/3 adrenal. In women, on the other hand, the adrenal glands are the main source of male hormones, but testosterone also arises in [ovarium|ovarium]]. Androgens are endocrine excreted directly into [blood|create]], where they are transported bound to globulin, specifically SHBG. Next, the newly created testosterone diffuses into Sertoli cells, where it binds to the nuclear receptor and to ABP (which provides transport to the lumens) or turns into estradiol, which reverses into Leydig cells. Androgens are metabolised mainly in [liver|yeatres]] and their metabolites are excreted urine.

Secretion control
right|250px|thumb| Osa hypothalamus → hypofýza → testes The main regulatory mechanisms for the production of androgenic hormones are [hypothalamo-hypophysical system]] and local'  autocrinal and paracrinal signalling. These take place along the way:

LH a hCG
On the outer membrane of Leydig cells are abundantly represented (up to 15&thinsp;000 per cell) specific, high-affinity and low-capacity receptors for luteinizing hormone.

In experiments with laboratory rats, it was found that the concentration of testosterone in interstice and seed-forming ducts depends directly on the time elapsed since the application of LH antisera, and in connection with this intervention a significant increase in the number of locally produced hormones in interstice was observed, which were stimulated basally compared to hCG-stimulated testosterone production in isolated purified Leydig cells.

The maximum response occurs already when 1&thinsp;% of them are occupied, on the contrary, when oversuteering, there is a sudden reduction in their number. At the same time, a large part of the binding abilities are lost, for example, during fetal exposure of the testicles, fixation of the testicles in the abdomen or after binding khomaovodu. LH is the only hormone capable of activating steroidogenesis on its own even in in vitro conditions. While at low doses the effect of [in vivo]] is maximum, at large doses cells may be desensitated to both hCG and exogenous cAMP.

When LH is bound to the receptor, adenylate cyclase is stimulated, causing increased formation in the cell cAMP. This activates protein kinase, which ensures biosynthesis of specific [protein]]. Other messengers are also involved in the activation of protein kinase: cGMP and Ca2+. At the same time, the activity of enzymes, which is involved in the fission of the lateral chain cholesterolu and its release from the ester binding, is also stimulated. The population of Leydig cells is heterogeneous and therefore does not respond to uniform stimulation. When high hCG levels occur, the cleavage of the lateral cholesterol chain is blocked, while long-term mild stimulation has a positive effect – causing proliferation of Leydig cell organelles (mainly smooth endoplasmic reticulia, mitochondria and Golgi complex).

Estradiol
Locally produced estradiol can be a mediator of desensibilation processes and its level reacts sensitively to hCG stimulation (its level is maximum after only two hours). Estrogens also inhibit the production of progesteroneu.

Adenohypofyzární hormones
Unlike Sertoli cells, cells do not have Leydig receptors for FSH, but they carry receptors for prolactin'. However, it can only act synergistically in the current presence of LH. Prolactin probably increases the affinity of LH to the receptor while affecting lipid metabolism by mobilizing cholesterol esters and stimulating some steroidogenesis enzymes. However, too high levels act on testosterone synthesis inhibition.

Substances produced directly by the testicles
This group includes, for example, an inhibitor of binding LH to a receptor, gonadokinin, inhibin... These substances have largely slowing down to stopping estrogen production.

Other substances and influences
Steroidogenesis is hampered by ACTH, glucocorticoids and stressem, as well as the effect of serotonin and its metabolites on endocrine function of the testicles.

Mechanism of action
Androgenic hormones, like other tissue agents of steroid origin at the site of development, are collected only minimally, most steroidogenese products are extruded into the blood immediately after formation. Testosterone (or DHEA) passively diffuses into the cells of the target tissue, where it binds to the androgen receptor and then forms a complex hormone-receptor that enters the nucleus, induces the formation of a new mRNA and thus the formation of a specific protein.

Biological effects of testosterone

 * 1) Testosterone has an indispensable function in the embryonic period, when it determines the development of the male phenotype (and in the last two months of the embryonic period initiates the descent of the testicles into the scrot).
 * 2) It is necessary for the growth of the genital organs and the appearance of secondary sex characteristics (pubic hair, mutations), which manifest themselves most strongly during [puberty|puberty]], when its level gradually increases.
 * 3) In men it stimulates spermatogenesis.

This fact was experimentally verified in 1968, when the presence of androgens (both testosterone and DHEA) in rabbit epididymis was first demonstrated. That same year, these steroids were also detected in an excrement from a caput epididymis ram. In 1969, testosterone synthesis was described [in vitro]] from radioactive precursors from rat supervarlation. (The different concentrations of these hormones in the individual sections of the epididymis are dealt with in study A. I. Frankel and K.B. Eik from 1970!).

In addition, it affects male sexual behavior and promotes proteosynthesis with its anabolic effects. At the same time, it amplifies the formation of quest (increases bone mass volume and deposition calcia] and stimulates muscle growth. At its elevated level, a negative effect on the quality of the skin (formation of acne is manifested. It also increases erythropoiesis through increased secretion erythropoietinu.

Developmental and functional disorders associated with variations in testosterone production

 * 1) Pseudopubertas' is a false form prepared puberty starting in boys before year 9 and in girls before the 8th year of life. One of the causes of its formation may be the autonomic overproduction of sex hormones in the gonáds or adrenal glands. During treatment, the main goal is to prevent premature cessation of growth.
 * 2) Delayed puberty' is called the absence of signs of sexual adolescence in boys over 14 and girls over 13. On the contrary, it is caused by a reduced level of sex hormones and we treat it by substitution.
 * 3) Anorchia' we speak of if in the absence of one or both testicles. In bilateral anorexia, the testicles do not disappear until after the 16th gestation week. Although the affected has a mascululized external genitalia, it is sterile and due to low production of androgens is characterized by a eunuchoid habitat. Testosterone should be substituted for life.
 * 4) Kryptorchism, found in 5&5% of boys born, persists after the 1st year of life in almost 1/5 of them. Testicles are often dystopian or ectopic in the usual path of descent. Testosterone production is maintained, but there is a risk of gradual deterioration of spermiogenesis. At the same time, it increases them by up to 30 times the risk |[malignancies]] reversal.
 * 5) [Klinefelter syndrome]] is produced by nondisjunction of XY in meiosis. Classically, it is a gonadotype XXY, but there are also cases of multiple X or Y chromosomes. The frequency of occurrence is 1:500 live birth of boys. Typical are small (often azoospermic) testicles, eunuchoid growth due to low testosterone production and gynecomastia caused by increased estradiol formation. Pubic hair and beard are more steer.
 * 6) Male climacterin syndrome' (PADAM) is a natural decrease in endocrine activity testes from a certain age (see Figure 5) responsible for decreased libido, decrease in erectile dysfunction, loss of muscle mass and development of osteoporosis.
 * 7) Androgens Numbness Syndrome is conditioned by partial or complete depletion of the androgens receptor. It is genetically localized on the lous Xp11-12. Moris syndrome, when a woman's phenotype and psyche develop, but with a blind end vagina (testicular feminization syndrome). The prevalence of the disorder is 5/100&thinsp;000 women and its treatment consists in substitution of female hormones and removal of retinated testicles.

Related articles

 * Renin-angiotensin-aldosterone system
 * Steroid Hormone Synthesis

External references

 * Testosterone (Czech Wikipedia)
 * Testosterone (anglická wikipedie)

Source
Transferred with permission of the author Zlatka Vávrová.