Multiplicity of Progesterone's Actions and Receptors in the Mammalian Ovary1

Abstract

This minireview summarizes the role that progesterone (P4) plays in regulating granulosa and luteal cell function. These actions include the stimulation of P4 synthesis and the inhibition of estrogen synthesis, mitosis, and apoptosis. P4 also plays a key role in the ovulatory process. Although P4's actions are well documented, the mechanism or mechanisms that mediate all of these actions have not been defined. In addition to P4-induced gene transcription that is mediated by the nuclear P4 receptors (PGR-A and PGR-B), three other receptor/signal transduction pathways could account for P4's intraovarian actions. These pathways could be mediated by 1) the PGR localizing at or near the plasma membrane and activating SRC family kinases, 2) a membrane progestin receptor that responds to P4 by lowering intracellular cAMP and increasing MAPK 3/1 activity, and 3) a membrane receptor complex composed of serpine 1 mRNA binding protein (also known as PAIRBP1 or RDA288) and progesterone receptor membrane component 1. Ligand activation of this complex likely leads to an increase in protein kinase G activity, the maintenance of low basal intracellular free calcium, and the inhibition of granulosa and luteal cell mitosis and apoptosis. Given the complexity of P4's actions within the ovary, it is likely that all of these receptor/signal transduction pathways influence some aspect of ovarian function with the specific P4 response dependent on 1) the expression pattern of these putative P4 receptors, 2) the P4 binding affinity of each receptor system, and 3) the amount of available P4.