Regulatory factors of glucocorticoid binding in early and term rat placenta.
We have measured by an exchange procedure the binding of [3H]dexamethasone in cytosol of early (10-13 days) and late (19-22 days) placentas from pregnant rats. Binding was 3-fold higher in late placentas both in the presence of Na2MoO4. We then studied some possible regulatory factors in order to explain differences in binding at both gestational ages. The activity of enzymes compromising the phosphorylation (acid and alkaline phosphatases) or stability (protease) of the receptor were normal or lower in early as opposed to late placenta, discarding these enzymes as leading regulatory factors. Cyclic nucleotides were also studied, in view that they regulate steroid binding in uterus and placenta. Both basal and epinephrine-stimulated production of cAMP were higher in early placenta. cAMP (but not cGMP) inhibited [3H]dexamethasone binding by reducing the number of sites without changing the Kd. Moreover, addition of epinephrine in concentrations that maximally stimulated cAMP, inhibited subsequent binding of [3H]dexamethasone in cytosol. We suggest that cAMP may be a modulator of glucocorticoid binding at the early stages of placental development. The significance of this mechanism may be understood in terms of the opposing effects of cAMP and glucocorticoids on placental progesterone production.
D000818:Animals; D000242:Cyclic AMP / Q000494:pharmacology; D003907:Dexamethasone / Q000378:metabolism; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D007700:Kinetics; D008982:Molybdenum / Q000494:pharmacology; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011374:Progesterone / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D011965:Receptors, Glucocorticoid / Q000378:metabolism*
D011965:Receptors, Glucocorticoid; D011374:Progesterone; D003907:Dexamethasone; D008982:Molybdenum; C024687:sodium molybdate(VI); D000242:Cyclic AMP; D004837:Epinephrine