Inhibition of testosterone metabolism and lipogenesis in animal sebaceous glands by progesterone

Abstract

The effect of progesterone on 14C-testosterone metabolism and on 14C-lipid synthesis was studied in two animal sebaceous gland models, hamster flank organ and rat ear skin. Unilateral topical application of progesterone to the female hamster flank organ topically treated with testosterone propionate resulted in localized inhibition of both in vitro 14C-lipogenesis and in vitro conversion of 14C-testosterone to 5 alpha-reduced radio-metabolites. Topical progesterone did not inhibit in vitro 14C-lipogenesis in the male hamster flank organ. Progesterone added in vitro inhibited 14-C-lipogenesis and 14C-testosterone metabolism in male rat ear sebaceous glands. These results lend support to the hypothesis that inhibition of sebaceous gland lipogenesis by progesterone is a consequence of its inhibitory effect on testosterone metabolism. Such a rationale provides a valid explanation for the clinical findings with progesterone reported by other investigators.

Molecular interactions of natural and synthetic steroids in female hamsters’ flank organs

“…LNG is a progestational agent that inhibits 5a-reductase enzyme in the same way as P [3,27]. However, the results obtained in this experiment showed that topical treatment with T + LNG to the flank organs increased the diameter of the pigmented spot, as compared to the effect for T + P-treatment.…”

“…When 6 which is inactive as such, increased the effect of P; it appeared to show an uncompetitive antagonism for the expression of PIS and SQS [27]. The different response observed here, could be the result of a different conformation adopted by the PR in the presence of P or 6 or both together.…”

“…Treatment of the flank organs with P plus 6 produced an uncompetitive synergistic effect [27] for the mRNA expression of GPAT, HMGCoA-S, HMGCoA-R; but this was not the case for PIS and SQS. When 6 which is inactive as such, increased the effect of P; it appeared to show an uncompetitive antagonism for the expression of PIS and SQS [27].…”

The International Workshop on Meibomian Gland Dysfunction: Report of the Subcommittee on Anatomy, Physiology, and Pathophysiology of the Meibomian Gland

“…146,181,300 However, earlier and later studies disagreed, finding that progestin administration had no effect on sebaceous gland output, 191,300 and still others reported that these hormones reduce sebaceous gland function by inhibiting local androgen metabolism and activity. [301][302][303][304] One explanation of these conflicting findings is that progestin's effect on different types of sebaceous glands seem to be significantly influenced by the dose, endocrine environment, and the subject's sex. 302,[305][306][307] Progestin Regulation of the Meibomian Gland.…”

Contribution à l'étude expérimentale de la séborrhée. Implications éventuelles en cosmétologie

“…La lipogtndse skbacte. L'activitd de la glande sdbacee est itudiee au niveau de la synthbse des lipides partir du glucose marque au carbone-14, apr6s des applications topiques d'androgbnes reahsees sur l'organe de flanc (OF) du hamster femelle ou du hamster male castrd pendant le temps de 3 semaines (8,9).…”