Human Biochemistry, Volume 2 - Murray R. 1993

Biochemistry of Intracellular and Intercellular Communications
Sex Gland Hormones
Mechanism of Action of Testicular Hormones

Current views on The Mechanism of androgen action are illustrated in Fig. 50.4. Free testosterone enters Cells across Cell/30.html">The Plasma Membrane via passive or Facilitated Diffusion. Target cells retain testosterone, a process apparently mediated by the binding of the hormone to a specific intracellular receptor. Despite significant variations among different Tissues, in most of them the retained hormone is found in the Cell Nucleus. The Cytoplasm of many (though not all) target cells contains the enzyme 5a-reductase, which converts testosterone to DHT. Evidence regarding the existence of separate receptors for testosterone and DHT remains contradictory; however, there is general agreement that, even if a single Class of receptors exists, their affinity for DHT exceeds that for testosterone. In mice, a single-Gene mutation results in a failure of both testosterone and DHT to bind to the receptor in various tissues. This finding strongly suggests the presence of a single protein receptor for both Hormones. Which of the two complexes (testosterone-receptor or DHT-receptor) becomes active likely depends on differences in receptor affinity for these hormones, combined with the capacity of target tissues to convert testosterone into DHT.

For androgens to function, the testosterone/DHT-receptor complex must enter The Nucleus. The binding of this complex to Chromatin is presumably preceded by an activation step, during which chromatin exhibits a certain degree of Specificity or acceptor function. The precise Nature of the nuclear acceptor for the receptor-steroid complex has not yet been established.

Similar to other steroid (and certain peptide) hormones, the testosterone/DHT-receptor complex appears to activate specific genes whose protein products mediate many, if not all, of the hormone's effects. Testosterone stimulates Protein Synthesis in Male reproductive Organs. This effect is typically associated with the accumulation of total cellular RNA, including mRNA, tRNA, and rRNA. A more specific example is The Effect of testosterone on ABP synthesis. The hormone enhances the METABOLISM/31.html">Transcription of the ABP gene, thereby increasing the level of mRNA encoding this protein.

Another well-studied example is a_2u-globulin, the major urinary protein excreted by male rats. It is synthesized in the Liver of sexually mature males (older than 40 days). In females and castrated males, this protein is synthesized only if the animal receives testosterone. Estrogens suppress The production of a_2u-globulin, whereas its maximum synthesis requires the synergistic action of multiple hormones, including gonadotropins, THYROID HORMONES, Insulin, and glucocorticoids. The rate of a_2u-globulin synthesis directly correlates with the Abundance of its mRNA, which in turn depends on the transcription rate of the a_2u-globulin gene.

The Kidneys serve as a major target tissue for androgens. These hormones induce renal hypertrophy and stimulate the synthesis of several Enzymes across various animal species.

It is quite possible that complex androgen effects, such as their regulation of glandular secretory activity or Muscle hypertrophy, operate via a different mechanism. Furthermore, androgens are known to stimulate cell proliferation in certain target tissues—an effect that still lacks a definitive explanation. Testosterone or DHT, in combination with E₂, appears to be involved in The Development of benign prostatic hyperplasia (a condition affecting 75% of men over the age of 60).