Field experiences in comprehensive health planning.

Gordon, Carol; Chabot, André

doi:10.2105/ajph.62.7.973

Cited by 1 publication

(1 citation statement)

References 4 publications

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“…It is interesting to note that maca root, which is a natural herb indigenous to the Peruvian region, is routinely consumed by high-altitude individuals as a potential therapy to lower hematocrit, but the mechanistic basis for its action is unclear 78 . It is possible that maca root interacts with sex hormones, which results in changes in hematocrit.…”

Section: Discussionmentioning

confidence: 99%

Protective role of estrogen against excessive erythrocytosis in Monge’s disease

et al. 2021

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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 < 0.01) and its target genes (Alas2, BclxL, and Epor, p < 0.001). These changes result in a significant increase in apoptosis of erythroid cells. We also demonstrate that estrogen regulates erythropoiesis in CMS patients through estrogen beta signaling and that its inhibition can diminish the effects of estrogen by significantly increasing HIF1, VEGF, and GATA1 mRNA levels. Taken altogether, our results indicate that estrogen has a major impact on the regulation of erythropoiesis, particularly under chronic hypoxic conditions, and has the potential to treat blood diseases, such as high altitude severe erythrocytosis.

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Section: Discussionmentioning

confidence: 99%