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KMID : 0620920210530010125
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Experimental & Molecular Medicine
2021 Volume.53 No. 1 p.125 ~ p.135
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Protective role of estrogen against excessive erythrocytosis in Monge’s disease
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Azad Priti
Villafuerte Francisco C.
Bermudez Daniela
Patel Gargi
Haddad Gabriel G.
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Abstract
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Monge’s disease (chronic mountain sickness (CMS)) is a maladaptive condition caused by chronic (years) exposure to high-altitude hypoxia. One of the defining features of CMS is excessive erythrocytosis with extremely high hematocrit levels. In the Andean population, CMS prevalence is vastly different between males and females, being rare in females. Furthermore, there is a sharp increase in CMS incidence in females after menopause. In this study, we assessed the role of sex hormones (testosterone, progesterone, and estrogen) in CMS and non-CMS cells using a well-characterized in vitro erythroid platform. While we found that there was a mild (nonsignificant) increase in RBC production with testosterone, we observed that estrogen, in physiologic concentrations, reduced sharply CD235a+ cells (glycophorin A; a marker of RBC), from 56% in the untreated CMS cells to 10% in the treated CMS cells, in a stage-specific and dose-responsive manner. At the molecular level, we determined that estrogen has a direct effect on GATA1, remarkably decreasing the messenger RNA (mRNA) and protein levels of GATA1 (p?
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KEYWORD
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Haematopoietic stem cells, Myeloproliferative disease
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