Predominance of type I 5alpha-reductase in apocrine sweat glands of patients with excessive or abnormal odour derived from apocrine sweat (osmidrosis).
High levels of 5alpha-reductase activity have been detected in human apocrine glands, and the concentration of dihydrotestosterone has been found to be higher than that of testosterone in the nuclear fraction of the skin of patients who suffer from excessive or abnormal odour derived from apocrine sweat (osmidrosis). Although these results suggest that 5alpha-reductase may play a central role in the action of androgens in the apocrine gland, the isozyme responsible is not known. We therefore assayed 5alpha-reductase type I and type II activity and mRNA expression in isolated apocrine glands from four patients with osmidrosis. When we incubated gland homogenates with [3H]testosterone, we found that the biochemical properties of the apocrine gland enzyme were consistent with those of type I 5alpha-reductase: at substrate concentrations of both 50 nmol/L and 1 micromol/L, the optimum pH was in the range 6.0-7.5, and the apparent Km was 21.1 micromol/L. The apocrine gland enzyme was inhibited by MK386, a specific inhibitor of type I 5alpha-reductase, in a dose-dependent manner, but it was hardly affected by finasteride, a specific inhibitor of type II isozyme, in that a nanomolar concentration of finasteride produced only a slight inhibition. Reverse transcriptase-polymerase chain reaction showed that the apocrine gland expressed type I 5alpha-reductase mRNA exclusively, except for a faint band of type II isozyme in a few preparations. These data indicate that the type I isozyme is the predominant form of 5alpha-reductase in the apocrine gland and may play a central role in the anabolic activity of androgens, as reported for the sebaceous gland. In addition, a small amount of type II isozyme may be expressed by mesenchymal cells that surround the apocrine glands and also contribute to their development.
Sato
T
T
Department of Dermatology, Oita Medical University, 1-1, Idaiga-oka, Hazama-machi, Oita-gun, Oita 879-55, Japan.
Sonoda
T
T
Itami
S
S
Takayasu
S
S
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D058891:5-alpha Reductase Inhibitors; D000293:Adolescent; D001050:Apocrine Glands / Q000201:enzymology*; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D005260:Female; D015870:Gene Expression; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D009812:Odorants; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013543:Sweat Gland Diseases / Q000201:enzymology*; D013739:Testosterone / Q000494:pharmacology
D058891:5-alpha Reductase Inhibitors; D007527:Isoenzymes; D012333:RNA, Messenger; D013739:Testosterone; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase