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This version published online on August 25, 2005
Endocrinology, doi:10.1210/en.2005-0759
A more recent version of this article appeared on December 1, 2005
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Submitted on June 22, 2005
Accepted on August 19, 2005

Expression and Regulation of Progestin Membrane Receptors in the Rat Corpus Luteum

Zailong Cai and Carlos Stocco*

Department of Obstetrics, Gynecology and Reproductive Science, Yale School of Medicine, New Haven, CT 06520

* To whom correspondence should be addressed. E-mail: carlos.stocco{at}yale.edu.

Despite evidence strongly supporting progesterone's autocrine actions in the rat corpus luteum (CL), classical progesterone receptors (PR) have not been detected in this gland. Alternatively, in several other systems, progestins have been reported to activate non-genomic pathways via putative progestin membrane receptors (PMRs). The aim of this investigation was to determine whether rat CL membranes bind progestins and contain PMR homologs, and whether these proteins are expressed during CL development in a manner that parallels luteal function. We found that luteal cell membranes specifically bind progesterone. Low levels of progesterone and 20{alpha}-dihydroprogesterone decreased binding of 3H-progesterone, whereas androstendione, 17{alpha}-hydroxyprogesterone, and pregnenolone were less potent. Other steroids, including corticosterone, mifepristone, and estradiol, were ineffective. We found that the rat CL expresses five genes previously postulated to encode for putative PMRs: PMR{alpha}, PMR{beta}, PMR{gamma}, PR membrane component 1 (PRMC1), and Rda288. Pmr{alpha}, Pmr{gamma}, and Prmc1 transcripts rose steadily during pregnancy whereas Pmr{beta} and Rda288 remained constant. Just before parturition, concomitant with falling progesterone levels, Pmr{alpha}, Pmr{beta}, and Prmc1 decreased. Luteal PMR{alpha} and PRMC1 protein levels were lower in samples taken at the end of pregnancy compared with mid-pregnancy samples. Ergocriptine, which inhibits the secretion of prolactin, the primary luteotrophic hormone in the rat CL, reduced Pmr{alpha}, Pmr{beta}, and Prmc1 expression significantly. Ergocriptine effects were prevented by co-administration of prolactin. These findings provide evidence for the expression and regulation of putative membrane-bound progestin binding proteins in the rat CL, a tissue that does not express detectable levels of nuclear progesterone receptors.
Key words: Corpus Luteum • Progesterone • Rat




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