Activation of Gq/11 in the Mouse Corpus Luteum Is Required for Parturition

Mice with a deletion of G alpha(q/11) in granulosa cells were previously shown to be subfertile. They also have a reduced ovulatory response due to a deficiency in the ability of the activated LH receptor to fully induce the granulosa cell progesterone receptor. Because this conditional deletion of G alpha(q/11) will interfere with the actions of any G protein-coupled receptor that activates G alpha(q/11) in granulosa or luteal cells, we sought to determine whether the actions of other hormones that contribute to fertility were also impaired. We focused our attention on prostaglandin F2 (PGF2), because this hormone is known to activate phospholipase C (a prominent G alpha(q/11) effector) in luteal cells and because the action of PGF2 alpha on luteal cells is the first step in the murine parturition pathway. Our data show that the conditional deletion of G alpha(q/11) from granulosa cells prevents the ability of PGF2 alpha to induce Akr1c18 in luteal cells. Akr1c18 codes for 20 alpha-hydroxysteroid dehydrogenase, an enzyme that inactivates progesterone. The PGF2 alpha-mediated induction of this enzyme towards the end of pregnancy increases the inactivation of progesterone and precipitates parturition in mice. Thus, the conditional deletion of G alpha(q/11) from granulosa/luteal cells prevents the progesterone withdrawal that occurs at the end of pregnancy and impairs parturition. This novel molecular defect contributes to the subfertile phenotype of the mice with a deletion of G alpha(q/11) from granulosa cells.