Actions and interactions of estradiol and retinoic acid in mouse anterior prostate gland.
Experiments were designed to define the ability of retinoic acid to block the estrogen-induced metaplasia in the mouse anterior prostate gland (coagulating gland), and to elucidate some of the biochemical correlates of the actions and interactions of these two compounds. In castrated mice, the estrogen-induced metaplasia of epithelial cells consisted of multi-layered, nonpolarized cells, which accumulated to fill the lumen of the acini. Retinoic acid had no discernable effect on epithelial morphology of castrates, but significantly reduced the estrogen-induced metaplasia. Likewise, the estrogen-induced increases in the prostatic wet weight, ratio of ribonucleic to deoxy ribonucleic acids (RNA/DNA) and glycosyltransferases, as well as the decreases in 21,000 and 28,000 Mr soluble proteins were prevented by retinoic acid; the retinoid had no effect on these various parameters when administered alone to castrates. In contrast, the cyclic 3',5'-adenosine monophosphate (cAMP)-dependent phosphorylations at 16,000, 18,000, and 25,000 Mr and the activities of the type II cAMP-dependent kinase were uniformly reduced by both estradiol and retinoic acid. Tests of the action of the anti-estrogen LY-156758 on estrogen and retinoid effects showed that for those parameters on which retinoic acid was anti-estrogenic, LY-156758 was also anti-estrogenic. However, the qualitatively similar effects of retinoic acid and estradiol, which were confined to selected aspects of protein phosphorylation, were not antagonized by LY-156758. It is concluded that in the mouse anterior prostate, retinoic acid has both anti-estrogenic and estrogenic actions, and the latter may occur independently of the estrogen receptor.
D000818:Animals; D002369:Castration; D004347:Drug Interactions; D004789:Enzyme Activation / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D005964:Glucosyltransferases / Q000032:analysis; D008297:Male; D008679:Metaplasia / Q000517:prevention & control; D051379:Mice; D009696:Nucleic Acids / Q000032:analysis; D009929:Organ Size / Q000187:drug effects; D010750:Phosphoproteins / Q000032:analysis; D010766:Phosphorylation; D010880:Piperidines / Q000494:pharmacology; D011467:Prostate / Q000032:analysis / Q000187:drug effects*; D011494:Protein Kinases / Q000032:analysis; D020849:Raloxifene Hydrochloride; D014212:Tretinoin / Q000494:pharmacology*
D009696:Nucleic Acids; D010750:Phosphoproteins; D010880:Piperidines; D020849:Raloxifene Hydrochloride; D004958:Estradiol; D014212:Tretinoin; D005964:Glucosyltransferases; D011494:Protein Kinases