Progestin signaling through mPRa in Atlantic croaker granulosa/theca cell cocultures and its involvement in progestin inhibition of apoptosis.

Endocrinology

PubMedID: 20962051

Dressing GE, Pang Y, Dong J, Thomas P. Progestin signaling through mPRa in Atlantic croaker granulosa/theca cell cocultures and its involvement in progestin inhibition of apoptosis. Endocrinology. 2010;151(12):5916-26.
Although there is substantial evidence that membrane progestin receptors (mPRs) perform a critical physiological role in meiotic maturation of fish oocytes, it is unknown whether they are also intermediaries in progestin signaling in the surrounding follicular cells. Here, we show that mPRa protein is located on the plasma membranes of both granulosa and theca cells (G/T cells) isolated from Atlantic croaker ovaries and is associated with the presence of a single high affinity, limited capacity, pertussis toxin-sensitive, specific progestin [17,20ß,21-trihydroxy-4-pregnen-3-one (20ß-S)] membrane binding site with the characteristics of mPRa. Treatment of G/T cells with 20ß-S caused rapid G protein activation and a transient, pertussis toxin-sensitive, decrease in cAMP levels, whereas the selective nuclear progesterone receptor agonist, R5020, did not cause G protein activation, consistent with previous reports on mPRa signaling. 20ß-S treatment decreased serum starvation-induced cell death in both G/T cells and in seatrout mPRa-transfected MDA-MB-231 cells, whereas R5020 was ineffective. Moreover, a selective mPRa agonist, 10-ethenyl-19-norprogesterone, mimicked the protective action of 20ß-S against cell death, which was lost upon knockdown of mPRa protein but not after progesterone receptor knockdown, further demonstrating an involvement of mPRa. Signaling molecules involved in inhibition of apoptosis, Erk and serine-threonine kinase, were activated in G/T cells by 20ß-S, which suggests a potential mechanism for mPRa inhibition of apoptosis. This is the first study to demonstrate endogenous mPR signaling in the ovarian follicle and to suggest a novel physiological role for mPRa in mediating the antiapoptotic actions of progestins in ovarian follicle cells.