title: Receptor-mediated gonadotropin action in the ovary. Demonstration of acute dependence of rat luteal cells on exogenously supplied steroid precursor (sterols) for gonadotropin-induced steroidogenesis.
abstract: Incubation of luteal cells with human, horse and rat sera, but not bovine sera resulted in enhanced basal and hCG-stimulated progesterone accumulation. The stimulatory effect of human or rat sera on basal, hCG- or 8 Br-cyclic AMP-induced progesterone synthesis in luteal cells was evident within 15-30 min after incubation, reaching a maximum after 3-4 h. The stimulatory effects of hCG and/or sera were blocked by inhibitors of RNA and protein synthesis. Similarly, lysosomotropic agents, chloroquine (100 microM) and ammonium chloride (10 mM), partly blocked the steroidogenic response of luteal cells to hCG and/or human or rat sera. Incubation of cells in the presence of 2-deoxyglucose, sodium azide and phenylmethylsulfonyl fluoride resulted in partial inhibition of progesterone secretion in response to hCG or sera. Fractionation of human or rat sera into various lipoprotein fractions demonstrated that LDL and HDL most effectively supported and potentiated the steroidogenic response to hCG. Lipoprotein-deficient serum, however, did not alter gonadotropin-induced steroid production. Incubation of luteal cells with increasing concentrations of h-LDL and h-HDL enhanced both basal and hCG-mediated steroidogenesis in a dose-related manner, although very high concentrations of these lipoproteins were inhibitory. Further, [3H]cholesterol from [3H]cholesteryl linoleate-LDL was incorporated into luteal cell progesterone and the extent of this incorporation was enhanced by hCG. Addition of excess unlabeled h-LDL, h-HDL, as well as r-HDL, drastically reduced the incorporation of radioactive label into progesterone. These studies suggest that (a) serum potentiation of steroidogenesis was due to presence of lipoproteins, mainly LDL and HDL, and (b) the lipoprotein-bound cholesterol is delivered into the luteal cells and utilized for steroidogenesis.
mesh_terms: D000818:Animals; D001769:Blood; D002417:Cattle; D002784:Cholesterol / Q000378:metabolism; D006063:Chorionic Gonadotropin / Q000378:metabolism* / Q000494:pharmacology; D003338:Corpus Luteum / Q000187:drug effects / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D006736:Horses; D006801:Humans; D007700:Kinetics; D011374:Progesterone / Q000096:biosynthesis; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011974:Receptors, LH; D013045:Species Specificity; D013256:Steroids / Q000096:biosynthesis*
chemical_list: D006063:Chorionic Gonadotropin; D011956:Receptors, Cell Surface; D011974:Receptors, LH; D013256:Steroids; D011374:Progesterone; D002784:Cholesterol; D000242:Cyclic AMP