Characterization of binding components for progesterone and 5alpha-pregnane-3,20-dione in the hamster uterus.
In the hamster uterus, a specific progesterone (pregn-4-ene-3,20-dione) receptor has been identified in the cytosol fraction. In the present study, we examined hamster uterine cytosol for the possible existence of specific macromolecules that bind the progesterone metabolite, 5alpha-pregnane-3,20-dione. When cytosol was analyzed by density-gradient centrifugation with sucrose-glycerol gradients and by Scatchard plot analysis of [(3)H]5alpha-pregnane-3,20-dione binding data, there was no evidence of specific binding components for this metabolite. In vivo treatment of proestrous hamsters with unlabeled progesterone, 5alpha-pregnane-3,20-dione, or cortisol for 1 hr revealed that only progesterone caused the depletion of progesterone-receptor sites from the uterine cytosol fraction. Incubation of uterine strips which had been preloaded with two different concentrations of [(3)H]-progesterone demonstrated that progesterone was metabolized to 5alpha-pregnane-3,20-dione and to a greater extent to 3alpha-hydroxy-5alpha-pregnan-20-one. The accumulation of 5alpha-pregnane-3,20-dione during progesterone metabolism appeared to be related to the availability of nonspecifically bound hormone. These studies (i) strongly suggest there is no specific receptor system for 5alpha-pregnane-3,20-dione in the uterine cytosol fraction, (ii) confirm the existence of a specific progesterone receptor in uterine cytosol, and (iii) provide evidence that progesterone itself mediates the uterine progestational response via interaction with a specific receptor system.
D000818:Animals; D002458:Cell Fractionation; D002499:Centrifugation, Density Gradient; D006224:Cricetinae; D003600:Cytosol / Q000378:metabolism; D005260:Female; D006854:Hydrocortisone / Q000378:metabolism; D011277:Pregnanediones / Q000378:metabolism*; D011374:Progesterone / Q000378:metabolism*; D011956:Receptors, Cell Surface; D014316:Tritium; D014599:Uterus / Q000378:metabolism* / Q000648:ultrastructure
D011277:Pregnanediones; D011956:Receptors, Cell Surface; D014316:Tritium; D011374:Progesterone; D006854:Hydrocortisone