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Molecular Mechanisms of Androstenediol in the Regulation of the Proliferative Process of Human Endometrial Cells

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Abstract

Proliferation in endometria of women with polycystic ovarian syndrome (PCOS) is increased, similar to the biosynthesis of androstenediol (estrogenic metabolite). As previously shown, in human endometrial cells, androstenediol increases CYCLIN Dl levels and KI67 and decreases P27 content. The objective of the present investigation was to determine the mechanisms by which androstenediol promotes endometrial cell-cycle progression. Estrogen receptor a (ERa) activation and changes in CYCLIN Dl and P27 levels were evaluated by Western blot in T-HESCand St-TIb endometrial cell lines, using receptor antagonists; activation of PI3K-protein kinase B (AKT) and mitogen-activated protein kinases-extracellular signal-regulated kinases (MAPK-ERK)l/2 pathways was evaluated using PI3K, MAPK/ERK kinase (MEK)l/2, and RNA-polymerase II inhibitors. The data showed that androstenediol treatment significantly increases CYCLIN Dl and decreases P27 levels through ERa activation (P <.05). In addition, an increase in AKT/ERKI/2 phosphorylations was determined (P <.05). In the presence of RNA-polymerase II inhibitor, phosphorylation of AKT/ERKI/2 decreased (P <.05), meaning that endometrial cells need transcriptional activity to activate the kinases involved. It was also observed that PI3K action is required for P27 and CYCLIN Dl changes. Therefore, the action of androstenediol in endometria depends on PI3K-AKT and MAPK-ERKI/2 pathways activation, together with cell transcriptional machinery. This could be of clinical significance, as in pathologies such as PCOS, increased endometrial levels of androstenediol together with a high prevalence of endometrial hyperplasia and adenocarcinoma have been reported.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, School of Medicine, University of Chile Clinical Hospital, Santos Dumont # 999, Santiago, 8380456, Chile

    Francisca Plaza-Parrochia PhD, Lorena Oróstica PhD, Paula Garc;ia BSc, Carolina Vera PhD, Carmen Romero PhD, Luis Valladares PhD & Margarita Vega PhD

  2. Institute of Nutrition and Food Technology, University of Chile, Macul, Chile

    Margarita Vega PhD

Authors
  1. Francisca Plaza-Parrochia PhD
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  2. Lorena Oróstica PhD
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  3. Paula Garc;ia BSc
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  4. Carolina Vera PhD
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  5. Carmen Romero PhD
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  6. Luis Valladares PhD
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  7. Margarita Vega PhD
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Correspondence to Margarita Vega PhD.

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Plaza-Parrochia, F., Oróstica, L., Garc;ia, P. et al. Molecular Mechanisms of Androstenediol in the Regulation of the Proliferative Process of Human Endometrial Cells. Reprod. Sci. 24, 1079–1087 (2017). https://doi.org/10.1177/1933719116678689

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