A Study of the Role of Membrane Progesterone Receptors during Pregnancy and Labor in Rats

Progesterone plays a key role in preparing the female body for pregnancy and maintaining it. Classical nuclear progesterone receptors (nPRs) have been identified in female reproductive organs, through which progesterone exerts numerous effects in these tissues. Recently, membrane progesterone receptors (mPRs) have also been discovered in the uterus, placenta, ovaries, and mammary glands of humans and animals. These receptors are hypothesized to play important roles in maintaining pregnancy and initiating labor, though their specific functions in these processes remain unclear. Earlier in our work, two compounds with affinity for different subtypes of mPRs but no interaction with nPRs were identified. Their effects were demonstrated in various cell types but were not studied in vivo. The primary goal of this study was to investigate the effects of one of these steroids (LS-01) on pregnancy maintenance in ovariectomized female rats using a classical Corner & Allen’s test, as well as on labor stimulation, to elucidate the role of mPRs. To analyze the main targets of the selective mPR ligand in the uterus, the expression of all five mPR subtypes, as well as nPRs and the progesterone receptor membrane component 1 (PGRMC1), was examined before, during, and after pregnancy. The results of this study revealed no effect of LS-01 on either pregnancy maintenance or labor stimulation in rats. However, the expression profile of progesterone receptors and its correlations with serum sex steroid concentrations suggests distinct roles for different mPR subtypes: progesterone, acting through mPRγ and nPRs, may promote pregnancy maintenance, while acting through mPRβ, it may facilitate labor initiation. To clarify the functions of different mPR subtypes in reproduction and its fine regulation, the search for ligands selective for each membrane receptor is advisable.