Induction of progesterone receptor by androgens in the mouse uterus

Abstract

The comparative abilities of 3 naturally occurring androgens to compete for [ 3H]estradiol-17β ([ 3H]E 2)-binding sites in uterine cytosol and to induce uterotrophic responses in immature female mice have been investigated. 5α-Androstane-3β,17β-diol (3β-diol), 5α-androstane-3α,17β-diol (3α-diol) and 5-androstene-3β,17β-diol (Δ5-diol) are all effective at diminishing cytoplasmic [ 3H]E 2 binding. Their relative effectiveness are in the order of 3β-diol > Δ5-diol = 3α-diol. When these steroids were injected intramuscularly (two 100–200 μg injections) into immature female mice (21 days old), they induced similar elevations of uterine dry weight, water content, cytosolic estrogen (ER) and progesterone (PR) receptor contents, and nuclear ER content as did estradiol-17β (E 2). 3β-Diol was the most effective steroid at inducing cytosolic and nuclear ER, and PR production in mouse uterus. Followed in effectiveness was Δ5-diol and 3α-diol. Unexpectedly, 3β-diol was found to be more potent than E 2 in stimulating uterine ER and PR increases. Nonetheless, the androgens are poorer stimulators of uterine dry weight increase and water retention than E 2 is. These results indicate that the androgens may interact with the ER system in the uterus to bring about the uterotrophic responses and 3β-diol is a more estrogenic steroid than Δ5-diol and 3α-diol in the mouse uterus.