Estrogen Uncouples Steroidogenesis from 3′,5′-Cyclic Adenosine Monophosphate Regulation in the Rabbit Corpus Luteum1

The hypothesis was investigated that estradiol, the luteotrophic hormone in the rabbit, uncouples luteal progesterone production from regulation by LH/cyclic AMP. Progesterone production by corpus luteum (CL) incubated with vehicle, 3-isobutyl-1-methyl-xanthine (IBMX), hCG, or hCG+IBMX was compared in pseudopregnant rabbits treated continuously with estradiol (estradiol-maintained), withdrawn from estradiol for 24-48 h (estradiol-withdrawn), or withdrawn and then replaced with estradiol for 6 or 24 h (estradiol-replaced). Progesterone production in estradiol-maintained rabbits was not altered by hCG and/or IBMX, but was stimulated significantly in estradiol-withdrawn rabbits.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 hCG was not attributable to impaired accumulation of cyclic AMP: basal and hCG-stimulated cyclic AMP concentrations were similar in luteal tissues of estradiol-maintained and estradiol-withdrawn rabbits. The loss of responsiveness to hCG was also not a consequence of maximal progesterone production: CL of estradiol-replaced (6 h) rabbits were also insensitive to hCG, and this occurred before progesterone production attained a maximal rate. We conclude that a striking feature of the luteotrophic action of estrogen is to uncouple the regulation of progesterone production from cyclic AMP.