Copyright: © 2026 by the authors. Licensee: Pirogov University.
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ORIGINAL RESEARCH

Postmenopausal change in MSCs sensitivity to testosterone, 17β-estradiol, and PTH are associated with impaired adipogenesis

Zinoveva AA , Bakhchinian E , Kamenkov SS , Shcherbakova LN , Bugerenko AE , Ogay DS , Voloshin NS , Chechekhina ES , Kulebyakin KYu
About authors

Lomonosov Moscow State University, Moscow, Russia

Correspondence should be addressed: Elizaveta S. Chechekhina
Lomonosovsky Prospect 27/1, Moscow, 119192, Russia; ur.usm.ym@seavonyov

About paper

Funding: the study was supported by the RSF grant 25-75-30005 “Regulation of Body’s Cell Renewal Processes, the Fundamentals for Long-term Maintenance of Functional Activity of Organs and Tissues, Human Health and Active Longevity”.

Author contribution: Zinoveva AA, Bakhchinian E — experiments on MSC differentiation, processing of the results; Kamenkov SS — MSC isolation and culturing, statistical data processing, manuscript writing; Shcherbakova LN — clinical phase management, biomaterial acquisition, interpretation of the results, manuscript editing; Bugerenko AE, Ogay DS — clinical phase management, biomaterial acquisition; Voloshin NS — adipogenic differentiation quantification; Chechekhina ES — study concept and design, MSC isolation and culturing, interpretation of the results, manuscript writing; Kulebyakin KYu — study concept and design, interpretation of the results, manuscript editing.

Compliance with ethical standards: the study was approved by the Ethics Committee of the Lomonosov Moscow State University (IRB00010587, protocol No. 4 dated 4 June 2018, protocol No. 9 dated 29 October 2018) was conducted in accordance with the principles of the Declaration of Helsinki. All the patients provided informed consent before biomaterial collection.

Received: 2026-03-09 Accepted: 2026-04-05 Published online: 2026-04-16
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The menopausal transition is accompanied by the decrease in estrogen levels and changes in the estrogen to androgen ratio, resulting in dysregulation of multipotent mesenchymal stem cell (MSCs) differentiation in the subcutaneous adipose tissue, reduction of their adipogenic potential, adipocyte hypertrophy, and metabolic disorder progression. Menopausal hormone therapy (MHT) is used to manage menopausal symptoms. However, the effects of exogenous hormones on MSCs are still poorly understood. The study aimed to assess adipogenic differentiation of the subcutaneous adipose tissue MSCs and their sensitivity to testosterone, 17β-estradiol, and parathyroid hormone (PTH) in postmenopause. A total of six patients with benign gynecological disorders were included in the study, among them two were of reproductive age, one was perimenopausal, and three were postmenopausal. The MSCs adipogenic differentiation was performed throughout 14 days with the addition of testosterone, 17β-estradiol, or PTH, 10 nM each, then the proportion of cells containing lipid droplets was assessed. The adipogenesis level in control samples was 26–30% in patients of childbearing age and 12–42% in postmenopausal ones, with the pronounced interindividual variability. Hormonal stimulation considerably suppressed MSCs adipogenesis in postmenopause: testosterone reduced adipogenesis to 46–56% of control levels, estradiol to 51–84%, PTH to 53–66%, while patients of childbearing age showed a less pronounced effect (65–85%). The obtained data demonstrate a shift in hormonal sensitivity of MSCs from subcutaneous adipose tissue in postmenopause and suggest that MHT may exert an additional inhibiting effect on adipogenesis through suppression of MSCs differentiation.

Keywords: testosterone, mesenchymal stem cells, 17β-estradiol, PTH, adipogenic potential, menopause, menopausal hormone therapy

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