Russian Journal of PhysiologyRussian Journal of PhysiologyРоссийский физиологический журнал им. И.М. Сеченова0869-81392658-655XThe Russian Academy of Sciences68740110.31857/S0869813925060028TFRKTKEXPERIMENTAL ARTICLESЭКСПЕРИМЕНТАЛЬНЫЕ СТАТЬИResearch ArticleA Study of the Role of Membrane Progesterone Receptors During Pregnancy and Labor in RatsИзучение роли мембранных рецепторов прогестерона в процессе беременности и родов у крысVodopetovaM. A.ВодопетоваМ. А.
Russian Federation
schelkunova-t@mail.ruDmitrievaA. D.ДмитриеваА. Д.
Russian Federation
schelkunova-t@mail.ruLevinaI. S.ЛевинаИ. С.
Russian Federation
schelkunova-t@mail.ruMorozovI. A.МорозовИ. А.
Russian Federation
schelkunova-t@mail.ruRubtsovP. M.РубцовП. М.
Russian Federation
schelkunova-t@mail.ruSmirnovaO. V.СмирноваО. В.
Russian Federation
schelkunova-t@mail.ruShchelkunovaT. A.ЩелкуноваТ. А.
Russian Federation
schelkunova-t@mail.ruLomonosov Moscow State UniversityМосковский государственный университет им. М.В. ЛомоносоваZelinsky Institute of Organic Chemistry, Russian Academy of SciencesИнститут органической химии им. Н.Д. Зелинского РАНEngelhardt Institute of Molecular Biology, Russian Academy of SciencesИнститут молекулярной биологии им. В.А. Энгельгардта РАН15062025111684786413072025Copyright ©; 2025, Russian Academy of SciencesCopyright ©; 2025, Российская академия наук2025Russian Academy of SciencesРоссийская академия наукhttps://journals.eco-vector.com/0869-8139/article/view/687401

Progesterone plays a major role in preparing the female body for and maintaining pregnancy. Classical nuclear progesterone receptors (nPRs) have been found in the female reproductive organs, through interaction with which progesterone exerts multiple effects in these tissues. Recently, membrane progesterone receptors (mPRs) have also been found in the uterus, placenta, ovaries, and mammary glands of humans and animals. It is assumed that these receptors fulfil important functions in the maintenance of pregnancy, in the initiation of labour. However, their role in these processes has not been studied. Earlier in our work, we identified two compounds that have affinity for mPRs of different subtypes but do not interact with nPRs. Their actions have been demonstrated in various cells but have not been studied in vivo. In this work, the main aim was to study the action of one of these steroids (LS-01) in a classical test for pregnancy maintenance in ovariectomised female rats and for stimulation of the labour process to identify the role of mPRs. To analyse the main targets of mPRs selective ligand action in utero, we examined the expression of all five mPRs subtypes as well as nPRs and the membrane component of the progesterone receptor (PGRMC1) before, during and after pregnancy termination. From this study, we did not detect an effect of LS-01 on either pregnancy maintenance or labour induction in rats. However, the study of progesterone receptor expression profile and correlations of this profile with serum sex steroid concentrations suggests a different role of membrane receptor subtypes: progesterone acting through mPRγ and nPRs may promote pregnancy maintenance, while acting through mPRβ may promote labour initiation. To identify the functions of different subtypes of mPRs in reproduction and the fine regulation of this process, the search for ligands selective for each membrane receptor is necessary.

Прогестерон выполняет главную роль в процессе подготовки женского организма к беременности и в ее сохранении. В женских репродуктивных органах обнаружены классические ядерные рецепторы прогестерона (nPRs), за счет взаимодействия с которыми прогестерон оказывает многочисленные эффекты в этих тканях. В последнее время обнаружены также мембранные рецепторы (mPRs) прогестерона в матке, плаценте, яичниках, молочных железах человека и животных. Предполагается, что эти рецепторы выполняют важные функции в сохранении беременности, в инициации родов. Однако их роль в этих процессах не изучена. Ранее нами были выявлены два соединения, имеющие сродство к mPRs разных подтипов, но при этом не взаимодействующие с nPRs. Их действие было продемонстрировано в различных клетках, но не было изучено in vivo. В настоящей работе главной целью было изучение действия одного из этих стероидов (LS-01) в классическом тесте на сохранение беременности у овариэктомированных самок крыс и на стимуляцию родового процесса для выявления роли mPRs. Для анализа главных мишеней действия селективного лиганда mPRs в матке была изучена экспрессия всех пяти подтипов mPRs, а также nPRs и мембранного компонента рецептора прогестерона (PGRMC1) до, в процессе и после окончания беременности. В результате проведенного исследования мы не выявили действия LS-01 ни на сохранение беременности, ни на стимуляцию родов у крыс. Однако изучение профиля экспрессии рецепторов прогестерона и корреляций этого профиля с концентрациями половых стероидов в сыворотке крови позволяет сделать предположение о разной роли подтипов мембранных рецепторов: прогестерон, действуя через mPRγ и nPRs, может способствовать сохранению беременности, а действуя через mPRβ, способствовать инициации родов. Для выявления функций разных подтипов mPRs в репродукции и тонкой регуляции этого процесса необходим поиск лигандов, селективных для каждого мембранного рецептора.

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