Testicular physiology

The testicles (testicles) of a healthy adult are paired, ovoid, 3.6-5.5 cm long and 2.1-3.2 cm wide. Each weighs about 20 g. Due to their location in the scrotum, these glands have a temperature 2-2.5 C lower than the temperature of the abdominal cavity, which promotes heat exchange of blood between a. spermatica and the superficial venous system. The venous outflow from the testicles and their appendages forms a plexus, the blood from which enters the renal vein on the left and the inferior genital vein on the right. The testicle is surrounded by a thick capsule consisting of 3 layers: visceral, tunica vaginalis, protein coat and internal, tunica vasculosa. The protein coat has a fibrous structure. The membranes contain smooth muscle fibers, the contraction of which promotes the movement of sperm into the epididymis. Under the capsule there are approximately 250 pyramidal lobules separated from each other by fibrous partitions. Each lobule contains several convoluted seminiferous tubules 30-60 cm long. These tubules account for more than 85% of the testicle's volume. Short straight tubes connect the tubules directly to the rete testis, from where sperm enters the duct of the epididymis. The latter, when straightened, reaches 4-5 m in length, and when coiled, forms the head, body, and tail of the epididymis. Sertoli cells and spermatocytes are located in the epithelium surrounding the lumen of the tubule. Leydig cells, macrophages, blood vessels, and lymphatic vessels lie in the interstitial tissue between the tubules.

Sertoli cylindrical cells perform many functions: barrier (due to close contacts with each other), phagocytic, transport (participation in the movement of spermatocytes to the lumen of the tubule) and, finally, endocrine (synthesis and secretion of androgen-binding protein and inhibin). Polygonal Leydig cells have an ultrastructure (pronounced smooth endoplasmic reticulum) and enzymes characteristic of steroid-producing cells.

The testicles play a major role in the physiology of reproduction in men. Thus, the acquisition of the male phenotype by the fetus is largely determined by the production of Müllerian inhibitory substance and testosterone by the embryonic testicles, and the appearance of secondary sexual characteristics during puberty and the ability to reproduce are determined by the steroidogenic and spermatogenic activities of the testicles.

Synthesis, secretion and metabolism of androgens. In their production, the testicles play a more important role than the adrenal cortex. Suffice it to say that only 5% of T is formed outside the testicles. Leydig cells are capable of synthesizing it from acetate and cholesterol. Synthesis of the latter in the testicles is probably no different from the process occurring in the adrenal cortex. The key stage in the biosynthesis of steroid hormones is the conversion of cholesterol to pregnenolone, which involves the cleavage of the side chain in the presence of NADH and molecular oxygen. Further conversion of pregnenolone to progesterone can occur in various ways. In humans, the predominant pathway is apparently the D ⁵ -pathway, during which pregnenolone is converted into 1 7a-hydroxypregnenolone and then into dehydroepiandrosterone (DHEA) and T. However, the D ⁴ -pathway through 17-hydroxyprogesterone and androstenedione is also possible. The enzymes of such transformations are 3beta-oxysteroid dehydrogenase, 17a-hydroxylase, etc. In the testicles, as in the adrenal glands, steroid conjugates (mainly sulfates) are also produced. The enzymes that cleave the side chain of cholesterol are localized in the mitochondria, while the enzymes that synthesize cholesterol from acetate and testosterone from pregnenolone are located in the microsomes. Substrate-enzyme regulation exists in the testicles. Thus, in humans, steroid hydroxylation in the 20th position is quite active, and 20a-oxymetabolites of progesterone and pregnenolone inhibit 17a-hydroxylation of these compounds. In addition, testosterone can stimulate its own formation, affecting the conversion of androstenedione.

The adult testicles produce 5 to 12 mg of testosterone per day, as well as the weak androgens dehydroepiandrosterone, androstenedione, and androstene-3beta,17beta-diol. Testicular tissue also produces small amounts of dihydrotestosterone, and aromatization enzymes are present, resulting in small amounts of estradiol and estrone entering the blood and seminal fluid. Although the Leydig cells are the main source of testicular testosterone, steroidogenesis enzymes are also present in other cells of the testis (tubular epithelium). They may be involved in creating the high local T levels required for normal spermatogenesis.

The testicles secrete T episodically rather than continuously, which is one of the reasons for the wide fluctuations in the level of this hormone in the blood (3-12 ng/ml in a healthy young man). The circadian rhythm of testosterone secretion ensures its maximum content in the blood in the early morning (at about 7 a.m.) and its minimum in the afternoon (at about 1 p.m.). T is present in the blood mainly as a complex with sex hormone-binding globulin (SHBG), which binds T and DHT with greater affinity than estradiol. The concentration of SHBG decreases under the influence of T and growth hormone and increases under the influence of estrogens and thyroid hormones. Albumin binds androgens less strongly than estrogens. In a healthy person, approximately 2% of serum T is in a free state, 60% is bound to SHBG and 38% to albumin. Both free T and T bound to albumin (but not SHBG) undergo metabolic transformations. These transformations are mainly limited to the reduction of the D4 ^- keto group with the formation of 3alpha-OH or 3beta-OH derivatives (in the liver). In addition, the 17beta-oxy group is oxidized to the 17beta-keto form. About half of the produced testosterone is excreted from the body as androsterone, etiocholanolone, and (to a much lesser extent) epiandrosterone. The level of all these 17-ketosteroids in the urine does not allow one to judge the production of T, since weak adrenal androgens also undergo similar metabolic transformations. Other excreted metabolites of testosterone are its glucuronide (the level of which in the urine of a healthy person correlates well with testosterone production), as well as 5alpha- and 5beta-androstane-Zalfa, 17beta-diols.

Physiological effects of androgens and their mechanism of action. The mechanism of physiological action of androgens has features that distinguish them from other steroid hormones. Thus, in the target organs of the reproductive system, kidneys and skin, T under the influence of the intracellular enzyme D4-5a ^- reductase is converted into DHT, which, in fact, causes androgenic effects: an increase in the size and functional activity of the accessory sexual organs, male-type hair growth and increased secretion of the apocrine glands. However, in skeletal muscles, T itself is capable of increasing protein synthesis without additional transformations. The receptors of the seminiferous tubules apparently have equal affinity for T and DHT. Therefore, individuals with 5a-reductase deficiency retain active spermatogenesis. By converting into 5beta-androstene- or 53-pregnesteroids, androgens, like progestins, can stimulate hematopoiesis. The mechanisms of androgen influence on linear growth and ossification of metaphyses have not been sufficiently studied, although the acceleration of growth coincides with an increase in T secretion during puberty.

In target organs, free T penetrates into the cytoplasm of cells. Where there is 5a-reductase in the cell, it is converted into DHT. T or DHT (depending on the target organ) binds to the cytosolic receptor, changes the configuration of its molecule and, accordingly, the affinity for the nuclear acceptor. The interaction of the hormone-receptor complex with the latter leads to an increase in the concentration of a number of mRNAs, which is due not only to the acceleration of their transcription, but also to the stabilization of the molecules. In the prostate gland, T also enhances the binding of methionine mRNA to ribosomes, where large quantities of mRNA enter. All this leads to the activation of translation with the synthesis of functional proteins that change the state of the cell.