Effects of estradiol, progesterone or cAMP on expression of PGRMC1 and progesterone receptor in a xenograft model of human endometrium and in endometrial cell culture

Marie Van Wynendaele, Charlotte Thieffry, Lucie Samain, Christophe E Pierreux, Donatienne Tyteca, Étienne Marbaix, Etienne Marbaix, Patrick Henriet
Steroids · 2023 · vol. 198 , pp. 109284 · doi:10.1016/j.steroids.2023.109284 · PMID:37487815 · W4385076488
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Estradiol and progesterone differentially regulated progesterone receptor and PGRMC1 expression in a human endometrium xenograft model, with estradiol increasing PGR and progesterone decreasing it, while effects on PGRMC1 were not significant.

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This study examined how estradiol, progesterone, and cAMP affect expression of the progesterone receptor genes PGRMC1 and PGR in human endometrium, using a human endometrium xenograft model that mimics cycle phases and primary endometrial stromal cell culture. The authors found a direct correlation between PGRMC1 and PGR expression during proliferative and secretory phases of cycling endometrium, but not during the menstrual phase. In the xenograft model, estradiol increased PGR expression and progesterone decreased it, while estradiol/progesterone did not significantly change PGRMC1 expression; in primary stromal cell culture, steroid effects on PGRMC1 were absent and PGR showed only a small estradiol-driven increase. The paper concludes that its experiments do not provide a major advance in understanding mechanisms of cyclic PGRMC1 variation, particularly with respect to ovarian steroid regulation. This paper is centrally about endometriosis in the context of progesterone-response dysregulation and suspected roles of PGRMC1 in endometrial disease, including endometriosis, though it is not a direct study of endometriosis lesions.

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Effects of estradiol, progesterone or cAMP on expression of PGRMC1 and progesterone receptor in a xenograft model of human endometrium and in endometrial cell culture (2023) Steroids — Vol. 198, p. 109284 [1-11] (2023) (2023) Steroids — Vol. 198, p. 109284 [1-11] (2023) Open Access - Adobe PDF - 2.02 MB - Authors - author Van Wynendaele, Marie UCLouvain - author Thieffry, Charlotte UCLouvain - author Samain, Lucie UCLouvain - author Pierreux, Christophe UCLouvain - author Tyteca, Donatienne UCLouvain - author Marbaix, Etienne UCLouvain - author - Abstract - Estradiol and progesterone are key regulators of the menstrual cycle. In the human endometrium, progesterone induces morphological changes required for blastocyst implantation. Dysregulated response to progesterone can lead to endometrial pathologies including uterine bleeding and endometriosis. Besides the canonical nuclear progesterone receptor (encoded by the PGR gene), alternative response pathways include Progesterone Receptor Membrane Component 1 (PGRMC1), suspected to be involved in pathogenesis of endometrial diseases. We previously reported the spatiotemporal profile of PGRMC1 expression in the human endometrium along the menstrual cycle, highlighting progressive increase and decrease during the proliferative and secretory phases, respectively. Here we directly addressed its regulation by estradiol and progesterone, with systematic comparison with regulation of PGR expression. We found a direct correlation between expression of both genes during the proliferative and secretory phases in the cycling endometrium, but not during the menstrual phase. In a xenograft model mimicking the cycle phases, estradiol significantly increased and progesterone significantly decreased PGR expression but changes were not significant for PGRMC1. Finally, we did not find any significant effect of the ovarian steroids on expression of PGR or PGRMC1 in primary culture of endometrial stromal cells, except for a small increase in PGR expression by estradiol. Altogether, our experiments do not allow a major advance in our understanding of the mechanisms of cyclic variation of PGRMC1 expression, in particular regarding potential regulation by the ovarian steroids. - Affiliations - APA - Chicago - FWB Van Wynendaele, M., Thieffry, C., Samain, L., Pierreux, C., Tyteca, D., Marbaix, E., & Henriet, P. (2023). Effects of estradiol, progesterone or cAMP on expression of PGRMC1 and progesterone receptor in a xenograft model of human endometrium and in endometrial cell culture. Steroids, 198, 109284 [1-11]. https://doi.org/10.1016/j.steroids.2023.109284 (Original work published 2023)

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MeSH descriptors

Progesterone Progesterone Progesterone Progesterone Progesterone Progesterone Receptors, Progesterone Receptors, Progesterone Receptors, Progesterone Receptors, Progesterone Receptors, Progesterone Receptors, Progesterone Cell Culture Techniques Cell Culture Techniques Cell Culture Techniques Cell Culture Techniques Endometrium Endometrium Endometrium Endometrium

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