The antiandrogenic effect of progesterone on the hamster flank organ

Abstract

Progesterone, topically applied, prevents the stimulation of the hamster flank organ by testosterone, but not by dihydrotestosterone. 5α-Dihydroprogesterone does not prevent stimulation by either of the two androgenic hormones. Neither progesterone nor 5α-dihydroprogesterone stimulate the flank organ to any extent. Implications on the use of progesterone in acne therapy are discussed. It is currently accepted that 5α-dihydrotestosterone (DHT), which is formed mostly in the target cells per se by the 5α-reduction of testosterone, is the active androgen which controls gene expression in the target organ. This mechanism of action has been described for the prostate gland and seminal vesicles (Bruchovsky & Wilson 1968a, b; Stern & Eisenfeld, 1969). It has also been documented that a similar mechanism may be operating in the hamster flank organ (Takayasu & Adachi, 1972), a sebaceous structure, which like the sebaceous gland in the human and other species is androgen dependent. It seems reasonable to assume that inhibition of 5α DHT formation may be an effective means to block androgen action. Therefore Voigt, Fernandez & Hsia (1970) tested a great number of steroids for their capacity to inhibit the conversion of testosterone to 5α DHT in microsomal suspensions of the skin. Of the two major inhibitors found, progesterone and 4-androstene-3-one 17α carboxylic acid, they examined the effect of the latter compound in the hamster flank organ test. The effect of progesterone on the hamster flank has not been documented yet but it is important to do so since not only has topical progesterone been used in acne therapy, but it has been claimed that 5α-dihydroprogesterone (DHP), which is formed from progesterone in the skin, interacts with the DHT receptor (Wright, Giacomini & Kirchhoffer, 1979). The latter finding may be irrelevant but alternatively it could mean that DHP has some intrinsic androgenic or antiandrogenic activity. In this paper we describe experiments demonstrating that neither DHP nor progesterone have any androgenic activity. However, progesterone completely prevents the androgenic action of testosterone on the hamster flank organ.