Regulation of the androgen receptor in human genital skin fibroblasts, with a review of sex steroid receptor regulation by homologous and heterologous steroids

Abstract

When normal human genital skin fibroblasts are cultured for 3 days with 2–3 nM methyltrienolone (R1881, a synthetic nonmetabolizable androgen), they augment their specific androgen-receptor activity (two- to four-fold) with a time pattern that is always most rapid in the first 24 h, usually peaks by 48 h, and often declines, sometimes substantially, in the third 24-h interval. The time pattern is highly reproducible within experiments on confluent monolayers and is not influenced by the presence or absence of 10% fetal calf serum in the medium, the temperature (37 vs. 40 °C) at which the incubation is conducted, or the basal activity (up to 40 fmol/mg protein) that is saturated by incubation for 30–45 min at 37 °C. It does appear to be influenced by an unusually rapid increase in the first 24 h and by nonconfluent density of the monolayers, but these factors do not explain the considerable interexperimental variation, within and among cell lines, under nominally identical conditions. The time pattern is interpreted to represent an initial phase of "up-regulation" that is followed by one of compensatory adjustment, despite a constant level of unmetabolized ligand. A review of sex steroid receptor regulation by homologous and heterologous sex steroids reveals numerous examples of apparently homologous regulatory behavior.