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

Autor: Daniella Bermutez, Gabriel G. Haddad, Gargi Patel, Francisco C. Villafuerte, Priti Azad
Rok vydání: 2021
Předmět:
Male
Vascular Endothelial Growth Factor A
0301 basic medicine
Erythrocytes
Clinical Biochemistry
Altitude Sickness
Biochemistry
Myeloproliferative disease
0302 clinical medicine
GATA1 Transcription Factor
Cells
Cultured
health care economics and organizations
Testosterone
education.field_of_study
Chemistry
Haematopoietic stem cells
Menopause
Chronic mountain sickness
030220 oncology & carcinogenesis
Molecular Medicine
Erythropoiesis
Female
medicine.symptom
Biotechnology
medicine.medical_specialty
medicine.drug_class
purl.org/pe-repo/ocde/ford#1.06.03 [https]
Population
Polycythemia
Article
03 medical and health sciences
health services administration
Internal medicine
Genetics
medicine
Humans
RNA
Messenger
education
Molecular Biology
business.industry
Estrogens
Monge's disease
Hypoxia (medical)
Hypoxia-Inducible Factor 1
alpha Subunit
medicine.disease
Estrogen
Erythrocytosis
Erythropoietin receptor
Monge’s Disease
030104 developmental biology
Endocrinology
business
Zdroj: Experimental & Molecular Medicine
ISSN: 2092-6413
1226-3613
DOI: 10.1038/s12276-020-00550-2
Popis: 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
Chronic mountain sickness: Female hormone provides protection The hormone estrogen protects against chronic mountain sickness (CMS) in pre-menopausal women and may prove valuable in treating the condition. People who live for years in high altitude mountain regions are susceptible to CMS because of prolonged oxygen deprivation. One factor in CMS is an over-production of red blood cells, thickening the blood and increasing the risk of strokes and cardiovascular diseases. Men are more likely to suffer CMS than women, although cases spike in females after menopause. Gabriel Haddad at the University of California in San Diego, USA, and co-workers used a cell culture model of CMS to demonstrate that estrogen provides protection against the disease. Estrogen significantly alters the expression and activity of red blood cell-related genes to regulate red blood cell levels by controlling cell death mechanisms.
Databáze: OpenAIRE
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