Effects of topically applied antiandrogenic compounds on sebaceous glands of hamster ears and flank organs
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 /sup 3/H-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.
- Research Organization:
- Research Laboratories of Schering AG, West Berlin (Germany, F.R.)
- OSTI ID:
- 6076077
- Journal Information:
- J. Invest. Dermatol.; (United States), Vol. 92:5
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
ANTIANDROGENS
BIOCHEMICAL REACTION KINETICS
GLANDS
MORPHOLOGY
SKIN
TESTOSTERONE
METABOLISM
ENZYME INHIBITORS
HAMSTERS
RECEPTORS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ANDROGENS
ANDROSTANES
ANIMALS
BODY
DRUGS
HORMONE ANTAGONISTS
HORMONES
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
KETONES
KINETICS
LABELLED COMPOUNDS
MAMMALS
MEMBRANE PROTEINS
ORGANIC COMPOUNDS
ORGANS
PROTEINS
REACTION KINETICS
RODENTS
STEROID HORMONES
STEROIDS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques