Estrogen uncouples steroidogenesis from 3',5'-cyclic adenosine monophosphate regulation in the rabbit corpus luteum.
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hCG, or hCG+IBMX was compared in pseudopregnant rabbits treated continuously with estradiol (estradiol-maintained), withdrawn from estradiol for 24-48 h (estradiol-withdrawn), or withdrawn and then replaced with estradiol for 6 or 24 h (estradiol-replaced).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in estradiol-maintained rabbits was not altered by hCG and/or IBMX, but was stimulated significantly in estradiol-withdrawn rabbits.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basal and hCG-stimulated cyclic AMP concentrations were similar in luteal tissues of estradiol-maintained and estradiol-withdrawn rabbits.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.
Townson
D H
DH
Department of Physiology, University of Michigan Medical School, Ann Arbor 48109-0622, USA.
Keyes
P L
PL
Kostyo
J L
JL
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D003338:Corpus Luteum / Q000187:drug effects / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011374:Progesterone / Q000096:biosynthesis; D011506:Proteins / Q000378:metabolism; D011555:Pseudopregnancy / Q000378:metabolism; D011817:Rabbits; D013256:Steroids / Q000096:biosynthesis*
D006063:Chorionic Gonadotropin; D010726:Phosphodiesterase Inhibitors; D011506:Proteins; D013256:Steroids; D011374:Progesterone; D004958:Estradiol; D000242:Cyclic AMP; D015056:1-Methyl-3-isobutylxanthine