Dihydrotestosterone and inhibitors of steroid 5α-REDUCTASE

Česká verzia

Authors: prof. MUDr. RNDr. Luboslav Stárka, DrSc.
Authors place of work: Endokrinologický ústav
Published in the journal: Urol List 2007; 5(3): 11-16

Summary

In most mammalians, dihydrotestosterone (DHT) is a product of reduction of testosterone by steroid 5α-reductase (5α-RD). It plays a crucial role in the process of sexual differentiation of external genitalia in man. An example of its insufficient production due the 5α-dehydrogenase deficit is the Imperato- McGinley syndrome, in which mutations in type 2 isoenzyme of 5α-reductase cause male pseudohermaphroditism. The affected 46XY individuals have normal to elevated plasma testosterone levels with decreased DHT levels. They have ambiguous external genitalia at birth so that they are believed to be girls and are often raised as such. However, Wolffian differentiation occurs normally and they have epididymides, vas deferens and seminal vesicles. Virilization occurs at puberty frequently due to high testosterone levels, often associated with gender role change. The prostate in adulthood is small and rudimentary, and facial and body hair is absent or decreased. Balding has not been reported. Partial deficiency of 5α-reductase presents with micropenis, which can be corrected by dihydrotestosterone treatment in case of relative deficit of DHT. In normal individuals higher local concentrations of DHT play a key role in benign prostate hyperplasia or prostate carcinoma, but also in the development of male body hair. Administration of type 2 5α-reductase inhibitor, finasteride, has shown effective in the treatment of prostate hyperplasia and of androgenetic alopecia or hirsutism. Until now the physiological effects of DHT on chondrocytes during long-bone growth plate closure, spermatogenesis, especially on the maturation of spermatozoa in epididymis, on sexual brain differentiation and its action as a neuroactive steroid or the association of its higher levels with homosexuality has not been explained in detail and deserves further studies.

Key words:
dihydrotestosteronesteroid 5α-reductase, Imperato-McGinley syndrome, sexual differentiation, micropenis, alopecia, prostate

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