Binding of testosterone to uterine components of the immature rat.

The mechanism of the uterotrophic and antiuterotrophic action of testosterone in the rat is unknown. Since testosterone does not compete with estradiol-170 for receptor sites, the possible direct interaction of testosterone with uterine components in the rat was investigated. Following the administration of [aH]testosterone to immature female rats, the hormone is selectively taken up by uterine nuclei and is retained for 15 to 30 min. Thereafter, the hormone is gradually released and is virtually eliminated from the uterine nuclei over a period of 2 hours. Very low levels of radioactivity are accumulated in nuclei of diaphragm and other tissues. The simultaneous administration of nonlabeled testosterone reduces the nuclear uptake of [“H]testosterone in the uterus by about 80% while it has no effect on the uptake of the labeled hormone by diaphragm nuclei. In the cytosol as well as the nuclear extract of the uterus, [aH]testosterone is bound to macromolecules which are excluded from Sephadex G-SO. The nuclear [aH]testosterone macromolecule complex is also excluded from Sephadex G-200. No association of [aH]testosterone to macromolecules in cytosol or nuclei of diaphragm was observed. Uptake and binding of [3H]testosterone to nuclear components were also demonstrated in vitro following incubation of uteri at 37” in Eagle’s Hela culture medium. Binding to nuclear components is highly specific for testosterone and the nuclear binding sites are saturated with low concentrations of the hormone. SLu-Dihydrotestosterone is much less effective than testosterone in competing with [3H]testosterone for the nuclear binding sites. Estradiol-170 reduces the nuclear accumulation of (aH]testosterone by only 20 to 30% while progesterone, cortisol, and cyproterone acetate at the concentrations used have no effect. Studies using cell-free systems indicate that binding of testosterone to cytoplasmic components is a prerequisite step for the transfer of the hormone to the nucleus. In vitro and in vivo studies show that the immature rat uterus lacks the capacity to convert testosterone to 5ac-dihydrotestosterone or estrogens, to any significant extent.