Effects of topically applied antiandrogenic compounds on sebaceous glands of hamster ears and flank organs.

Abstract

Growth of sebaceous glands in the ears and flank organs of castrated male hamsters is dependent on androgen substitution. Taking this for granted, a study was done to compare the effects of topical antiandrogenic treatment in vivo on the morphology and size of sebaceous glands with the concomitant changes in in vitro metabolism of 3H-testosterone. The role of dihydrotestosterone in sebaceous gland stimulation was thereby investigated. Topical treatment was carried out with the androgen antagonist 17 alpha-propylmesterolone (PM), with 4-androsten-3-one-17 beta-carboxylic acid (17 beta-C), and 17 beta-N,N-diethylcarbamoyl-4-methyl-4-aza-5 alpha-androstan-3-one (4-MA), both described as specific 4-steroid-5 alpha-reductase inhibitors, and with progesterone (PRO), which is an androgen receptor antagonist with 5 alpha-reductase inhibiting properties. Regrowth of sebaceous glands after castration and substitution with testosterone propionate or dihydrotestosterone could be inhibited by topical PM and PRO. This occurred irrespective of the influence on testosterone metabolism and irrespective of the mode of substitution. 4-MA, on the other hand, while exhibiting strong 5 alpha-reductase inhibition in vitro, was ineffective in reducing sebaceous gland sizes in vivo. The compound 17 beta-C was ineffective in every respect. In no case were systemic antiandrogenic effects on prostates and seminal vesicles observed. Our results support the view that the DHT formation rate has no regulatory function for growth of sebaceous glands in hamsters and that PM and PRO counteract the androgenic stimulus by their competitive antagonistic binding to the androgen receptor, but not by their influence on testosterone metabolism.