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Abstract <p>Progesterone plays a key role in preparing the female bodyfor pregnancy and maintaining it. Classical nuclear progesteronereceptors (nPRs) have been identified in female reproductive organs,through which progesterone exerts numerous effects in these tissues.Recently, membrane progesterone receptors (mPRs) have also beendiscovered in the uterus, placenta, ovaries, and mammary glandsof humans and animals. These receptors are hypothesized to playimportant roles in maintaining pregnancy and initiating labor, thoughtheir specific functions in these processes remain unclear. Earlierin our work, two compounds with affinity for different subtypesof mPRs but no interaction with nPRs were identified. Their effectswere demonstrated in various cell types but were not studied invivo. The primary goal of this study was to investigate the effectsof one of these steroids (LS-01) on pregnancy maintenance in ovariectomizedfemale rats using a classical Corner &amp; Allen’s test, as wellas on labor stimulation, to elucidate the role of mPRs. To analyzethe main targets of the selective mPR ligand in the uterus, theexpression of all five mPR subtypes, as well as nPRs and the progesteronereceptor membrane component 1 (PGRMC1), was examined before, during,and after pregnancy. The results of this study revealed no effectof LS-01 on either pregnancy maintenance or labor stimulation inrats. However, the expression profile of progesterone receptorsand its correlations with serum sex steroid concentrations suggestsdistinct roles for different mPR subtypes: progesterone, actingthrough mPRγ and nPRs, may promote pregnancy maintenance, whileacting through mPRβ, it may facilitate labor initiation. To clarifythe functions of different mPR subtypes in reproduction and itsfine regulation, the search for ligands selective for each membranereceptor is advisable.</p>

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

  • 期刊论文

  • 发表日期：

    2025年3月1日

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  • M. A. Vodopetova,
  • A. D. Dmitrieva,
  • I. S. Levina,
  • I. A. Morozov,
  • P. M. Rubtsov,
  • O. V. Smirnova,
  • T. A. Shchelkunova

摘要

Abstract

Progesterone plays a key role in preparing the female bodyfor pregnancy and maintaining it. Classical nuclear progesteronereceptors (nPRs) have been identified in female reproductive organs,through which progesterone exerts numerous effects in these tissues.Recently, membrane progesterone receptors (mPRs) have also beendiscovered in the uterus, placenta, ovaries, and mammary glandsof humans and animals. These receptors are hypothesized to playimportant roles in maintaining pregnancy and initiating labor, thoughtheir specific functions in these processes remain unclear. Earlierin our work, two compounds with affinity for different subtypesof mPRs but no interaction with nPRs were identified. Their effectswere demonstrated in various cell types but were not studied invivo. The primary goal of this study was to investigate the effectsof one of these steroids (LS-01) on pregnancy maintenance in ovariectomizedfemale rats using a classical Corner & Allen’s test, as wellas on labor stimulation, to elucidate the role of mPRs. To analyzethe main targets of the selective mPR ligand in the uterus, theexpression of all five mPR subtypes, as well as nPRs and the progesteronereceptor membrane component 1 (PGRMC1), was examined before, during,and after pregnancy. The results of this study revealed no effectof LS-01 on either pregnancy maintenance or labor stimulation inrats. However, the expression profile of progesterone receptorsand its correlations with serum sex steroid concentrations suggestsdistinct roles for different mPR subtypes: progesterone, actingthrough mPRγ and nPRs, may promote pregnancy maintenance, whileacting through mPRβ, it may facilitate labor initiation. To clarifythe functions of different mPR subtypes in reproduction and itsfine regulation, the search for ligands selective for each membranereceptor is advisable.