5-alpha-reductase deficiency (5-ARD) is a condition caused by a mutation of the 5-alpha reductase type 2 gene. This gene encodes an enzyme that converts testosterone to dihydrotestosterone (DHT). DHT is necessary for the development of male genitalia in utero, and the resulting DHT deficency results in ambiguous external genitalia at birth. The condition affects only chromosomal males (i.e., those with XY chromosomes). Individuals with 5-ARD lack a uterus and Fallopian tubes (due to the normal action of Mullerian inhibiting factor), and possess testes and Wolffian structures. Their external genitalia, however, can vary from normal male external genitalia, to ambiguous genitalia, to normal female genitalia (although with a tendency towards an enlarged clitoris). In the later cases the Wolffian ducts terminate in the perineum or in a pseudovagina. 5-ARD consitutes a variety of intersexualism.
Individuals with 5-ARD have XY chromosomes and testes, and tend to have a vagina and labia, but with a small penis capable of ejaculation instead of a clitoris (this penis, however, appears to be a clitoris at birth). These individuals are normally raised as girls. However, come puberty, their testes will descend, their voice will deepen and they often will develop a male sexual identity. But they develop only limited facial hair.
A prototype for 5alpha -reductase inhibitors is 17 beta -N,N-diethylcarbamoyl-4-methyl-4-aza-5 alpha -androstan-3-one (4-MA), which behaves as an inhibitor of 5alpha -reductase in vivo, decreasing the prostatic concentration of 5alpha -DHT in intact male rats or in castrated male rats given testosterone propionate.
The ability of gamma -linolenic acid to inhibit 5alpha -reductase in solubilized microsomes indicates that the gamma -linolenic acid inhibition may not be rigidly dependent on the native source of endoplasmic reticulum membranes.
5alpha -reductase inhibition using compositions of the present invention may also be utilized in such methods to provide a baseline control for determining the efficacy of a candidate substance, as well as to test such a candidate substance for synergistically enhancing the 5alpha -reductase inhibitory activity of the compositions disclosed herein.
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