EFFECTERS OF CYCLIC ADENOSINE 5'-MONOPHOSPHATE UP-REGULATING-OXYTOCINRECEPTORS IN RABBIT AMNION CELLS - ISOPROTERENOL, PARATHYROID HORMONE-RELATED PROTEIN, AND POTENTIATION BY CORTISOL
Yj. Jeng et al., EFFECTERS OF CYCLIC ADENOSINE 5'-MONOPHOSPHATE UP-REGULATING-OXYTOCINRECEPTORS IN RABBIT AMNION CELLS - ISOPROTERENOL, PARATHYROID HORMONE-RELATED PROTEIN, AND POTENTIATION BY CORTISOL, Biology of reproduction, 53(5), 1995, pp. 1051-1056
Forskolin (FSK; an activator of adenylyl cyclase) and cortisol synergi
stically increase the concentration of oxytocin receptors (OTRs) in ra
bbit amnion cells. The aims of this study were to characterize potenti
al physiological regulators of OTR concentrations acting through adeny
lyl cyclase and to clarify the mechanisms of potentiation by cAMP and
cortisol. Both isoproterenol (ISO) and parathyroid hormone-related pro
tein (PTHrP) elevated amnion cell cAMP levels and OTR concentrations.
The effects of ISO and PTHrP on OTR were potentiated by cortisol. Cort
isol had no effect on the ability of ISO or PTHrP to stimulate adenyly
l cyclase activity, and cAMP did not affect the number or affinity of
glucocorticoid receptors in whole cells or in cytosol. Adenylyl cyclas
e activation, however, caused conversion of mifepristone (RU486) from
a glucocorticoid antagonist to agonist. Thus, mifepristone elevated OT
R receptor concentrations in the presence of FSK. In contrast, a struc
turally related glucocorticoid antagonist, onapristone (ZK98 299), was
unaffected by cAMP. Because glucocorticoid receptors bound to mifepri
stone are capable of interacting with DNA, whereas onapristone-occupie
d receptors are not, we conclude that cAMP affects glucocorticoid rece
ptor-DNA interactions, accounting for the synergistic effects of cAMP
and cortisol on OTRs.