Дигидротестостерон: структура, функции и роль в организме

Human hormone
dihydrotestosterone as a hormone
5α dihydrotestosterone, an androgen

Dihydrotestosterone (DHT, 5α dihydrotestosterone, 5α DHT, androstanolone or stanolone) is an endogenous androgen sex steroid and hormone primarily involved in the growth and repair of the prostate and the penis, as well as the production of sebum and body hair composition. The enzyme 5α reductase catalyzes the formation of DHT from testosterone in certain tissues including the prostate gland, seminal vesicles, epididymides, skin, hair follicles, liver, and brain. This enzyme mediates reduction of the C4 5 double bond of testosterone. DHT may also be synthesized from progesterone and 17α hydroxyprogesterone via the androgen backdoor pathway in the absence of testosterone. Relative to testosterone, DHT is considerably more potent as an agonist of the androgen receptor (AR). In addition to its role as a natural hormone, DHT has been used as a medication, for instance in the treatment of low testosterone levels in men; for information on DHT as a medication, see the androstanolone article.

Much of the biological role of DHT has been elucidated in studies of individuals with congenital 5α reductase type 2 deficiency, an intersex condition caused by a loss of function mutation in the gene encoding 5α reductase type 2, the major enzyme responsible for the production of DHT in the body. It is characterized by a defective and non functional 5α reductase type 2 enzyme and a partial but majority loss of DHT production in the body. Nonetheless, males with 5α reductase type 2 deficiency exhibit signs of continued undervirilization in a number of domains. Facial hair was absent or sparse in a relatively large group of Dominican males with the condition, known as the Güevedoces. However, more facial hair has been observed in patients with the disorder from other parts of the world, although facial hair was still reduced relative to that of other men in the same communities. The divergent findings may reflect racial differences in androgen dependent hair growth. A female pattern of androgenic hair growth, with terminal hair largely restricted to the axillae and lower pubic triangle, is observed in males with the condition. No temporal recession of the hairline or androgenic alopecia (pattern hair loss or baldness) has been observed in any of the cases of 5α reductase type 2 deficiency that have been reported, whereas this is normally seen to some degree in almost all Caucasian males in their teenage years. Unlike males, genetic females with 5α reductase type 2 deficiency are phenotypically normal. However, similarly to genetic males with the condition, they show reduced body hair growth, including an absence of hair on the arms and legs, slightly decreased axillary hair, and moderately decreased pubic hair. This is in accordance with the fact that sebum secretion appears to be entirely under the control of 5α reductase type 1. As such, similarly to the case of 5α reductase type 2 deficiency, they provide useful insights in the elucidation of the biological functions of DHT. 5α Reductase inhibitors were developed and are used primarily for the treatment of BPH. The drugs are able to significantly reduce the size of the prostate gland and to alleviate symptoms of the condition. Long term treatment with 5α reductase inhibitors is also able to significantly reduce the overall risk of prostate cancer, although a simultaneous small increase in the risk of certain high grade tumors has been observed. In addition to prostate diseases, 5α reductase inhibitors have subsequently been developed and introduced for the treatment of pattern hair loss in men. They are able to prevent further progression of hair loss in most men with the condition and to produce some recovery of hair in about two thirds of men. Aside from pattern hair loss, the drugs are also useful in the treatment of hirsutism and can greatly reduce facial and body hair growth in women with the condition. 5α Reductase inhibitors are overall well tolerated and show a low incidence of adverse effects. Sexual dysfunction, including erectile dysfunction, loss of libido, and reduced ejaculate volume, may occur in 3.4 to 15.8% of men treated with finasteride or dutasteride. A small increase in the risk of affective symptoms including depression, anxiety, and self harm may be seen. Both the sexual dysfunction and affective symptoms may be due partially or fully to prevention of the synthesis of neurosteroids like allopregnanolone rather necessarily than due to inhibition of DHT production. A small risk of gynecomastia has been associated with 5α reductase inhibitors (1.2–3.5%). Based on reports of 5α reductase type 2 deficiency in males and the effectiveness of 5α reductase inhibitors for hirsutism in women, reduced body and/or facial hair growth is a likely potential side effect of these drugs in men. Whereas 5α reductase type 2 inhibitors achieve much higher reductions in circulating DHT production, MK 386 decreases circulating DHT levels by 20 to 30%. Conversely, it was found to decrease sebum DHT levels by 55% in men versus a modest reduction of only 15% for finasteride. However, MK 386 failed to show significant effectiveness in a subsequent clinical study for the treatment of acne.

DHT is a potent agonist of the AR, and is in fact the most potent known endogenous ligand of the receptor. It has an affinity (Kd) of 0.25 to 0.5 nM for the human AR, which is about 2 to 3 fold higher than that of testosterone (Kd = 0.4 to 1.0 nM) and 15–30 times higher than that of adrenal androgens. In addition, the dissociation rate of DHT from the AR is 5 fold slower than that of testosterone. The EC50 of DHT for activation of the AR is 0.13 nM, which is about 5 fold stronger than that of testosterone (EC50 = 0.66 nM). In bioassays, DHT has been found to be 2.5 to 10 fold more potent than testosterone. A study of transdermal (patches) DHT and testosterone treatment reported terminal half lives of 2.83 hours and 1.29 hours, respectively. Unlike other androgens such as testosterone, DHT cannot be converted by the enzyme aromatase into an estrogen like estradiol. Therefore, it is frequently used in research settings to distinguish between the effects of testosterone caused by binding to the AR and those caused by testosterone's conversion to estradiol and subsequent binding to and activation of ERs. Although DHT cannot be aromatized, it is still transformed into metabolites with significant ER affinity and activity. These are 3α androstanediol and 3β androstanediol, which are predominant agonists of the ERβ.]]