title: Higher androgen bioactivity is associated with excessive erythrocytosis and chronic mountain sickness in Andean Highlanders: a review.
abstract: Populations living at high altitudes (HA), particularly in the Peruvian Central Andes, are characterised by presenting subjects with erythrocytosis and others with excessive erythrocytosis (EE)(Hb>21 g dl(-1) ). EE is associated with chronic mountain sickness (CMS), or lack of adaptation to HA. Testosterone is an erythropoietic hormone and it may play a role on EE at HA. The objective of the present review was to summarise findings on role of serum T levels on adaptation at HA and genes acting on this process. Men at HA without EE have higher androstenedione levels and low ratio androstenedione/testosterone than men with EE, suggesting low activity of 17beta-hydroxysteroid dehydrogenase (17beta-HSD), and this could be a mechanism of adaptation to HA. Higher conversion of dehydroepiandrosterone to testosterone in men with EE suggests nigher 17beta-HSD activity. Men with CMS at Peruvian Central Andes have two genes SENP1, and ANP32D with higher transcriptional response to hypoxia relative to those without. SUMO-specific protease 1 (SENP1) is an erythropoiesis regulator, which is essential for the stability and activity of hypoxia-inducible factor 1 (HIF-1α) under hypoxia. SENP1 reverses the hormone-augmented SUMOylation of androgen receptor (AR) increasing the transcription activity of AR.In conclusion, increased androgen activity is related with CMS.
authors.affiliation: Laboratory of Endocrinology and Reproduction, High Altitude Research Institute and Department of Biological and Physiological Sciences, Faculty of Sciences and Philosophy, Universidad Peruana Cayetano Heredia, Lima, Peru.
authors.forename: G F
authors.initials: GF
authors.lastname: Gonzales
authors.affiliation: Laboratory of Endocrinology and Reproduction, High Altitude Research Institute and Department of Biological and Physiological Sciences, Faculty of Sciences and Philosophy, Universidad Peruana Cayetano Heredia, Lima, Peru.
authors.forename: D
authors.initials: D
authors.lastname: Chaupis
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics; D000532:Altitude Sickness / Q000097:blood* / Q000235:genetics / Q000503:physiopathology; D000728:Androgens / Q000097:blood* / Q000235:genetics; D002908:Chronic Disease; D006801:Humans; D008297:Male; D011086:Polycythemia / Q000097:blood*; D011944:Receptors, Androgen / Q000378:metabolism; D013020:South America
chemical_list: D000728:Androgens; D011944:Receptors, Androgen
keywords: Androgen receptor; SNEP1; chronic mountain sickness; como; haemoglobin; testosterone levels