ESTROGEN UNCOUPLES STEROIDOGENESIS FROM 3',5'-CYCLIC ADENOSINE-MONOPHOSPHATE REGULATION IN THE RABBIT CORPUS-LUTEUM

The hypothesis was investigated that estradiol, the luteotrophic hormo ne in the rabbit, uncouples luteal progesterone production from regula tion by LH/cyclic AMP, Progesterone production by corpus luteum (CL) i ncubated with vehicle, 3-isobutyl-1-methyl-xanthine (IBMX), hCG, or hC G + IBMX was compared in pseudopregnant rabbits treated continuously w ith estradiol (estradiol-maintained), withdrawn from estradiol for 24- 48 h (estradiol-withdrawn), or withdrawn and then replaced with estrad iol for 6 or 24 h (estradiol-replaced). Progesterone production in est radiol-maintained rabbits was not altered by hCG and/or IBMX, but was stimulated significantly in estradiol-withdrawn rabbits, This response was reversed (i,e,, abolished) in estradiol-replaced (24 h) rabbits, The loss of responsiveness to I ICG was not attributable to impaired a ccumulation of cyclic AMP: basal and hCG-stimulated cyclic AMP concent rations were similar in luteal tissues of estradiol-maintained and est radiol-withdrawn rabbits. The loss of responsiveness to hCG was also n ot a consequence of maximal progesterone production: CL of estradiol-r eplaced (6 h) rabbits were also insensitive to hCG, and this occurred before progesterone production attained a maximal rate. We conclude th at a striking feature of the luteotrophic action of estrogen is to unc ouple the regulation of progesterone production from cyclic AMP.