Differential effects of ventilatory stimulation by sex hormones and almitrine on hypoxic erythrocytosis

Favier, R.; Spielvogel, Hilde; Caceres, Esperanza; Rodríguez, Armando; Semporé, B.; Pequignot, J. M.; Péquignot, Jean-Marc

doi:10.1007/s004240050368

Cited by 17 publications

(21 citation statements)

References 26 publications

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“…This suggests that another hormone or factor was associated with EE at HAs. Testosterone decreases ventilation [12] and increases erythropoiesis [13], and both effects may be associated with EE. In fact, TT, cFT, and BAT were higher in the group with EE at HA than in the group without EE and with men at LA.…”

Section: Discussionmentioning

confidence: 97%

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High serum zinc and serum testosterone levels were associated with excessive erythrocytosis in men at high altitudes

et al. 2011

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Chronic mountain sickness (CMS), a lack of adaptation to altitude characterized by excessive erythrocytosis (EE), is a health problem associated with life at high altitude. The erythropoietic process is regulated by both erythropoietin and testosterone. Zinc (Zn) is known to be related with testosterone and hemoglobin levels; meanwhile, nitric oxide was also associated with adaptation to high altitude. The aim of this study was to determine the relationship of hemoglobin and CMS score with serum levels of zinc, total testosterone (TT), calculated free testosterone (cFT), bioavailable testosterone (BAT), hemoglobin, and nitric oxide in men at high altitude with or without EE. Men residing in Lima (150 m) and Cerro de Pasco (4,340 m), Peru, were divided into three groups: (1) low altitude, (2) high altitude without EE (hemoglobin < 21 g/dl), and (3) high altitude with EE (hemoglobin ≥ 21 g/dl). Adjusted multivariable regression models showed that serum testosterone (total or free) and Zn levels were independently correlated with increased hemoglobin levels. Similarly, hemoglobin was positively related with signs/symptoms of CMS; however, both increased the serum Zn and the nitric oxide levels correlated with reduced risk for signs/symptoms of CMS. In conclusion, higher serum testosterone levels and Zn levels were associated with EE, and low scores of signs/symptoms of CMS were associated with higher Zn and nitric oxide levels.

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Section: Discussionmentioning

confidence: 97%

“…Both higher erythropoiesis and hypoventilation are related with testosterone actions [12,13]. Therefore, it is suggested that testosterone may be involved in HA adaptation acting on both processes associated with CMS [14].…”

Section: Introductionmentioning

confidence: 96%

High serum zinc and serum testosterone levels were associated with excessive erythrocytosis in men at high altitudes

et al. 2011

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“…It has been observed that alveolar ventilation and hypoxic ventilatory responses are greater in females than in males and such differences have been attributed to ovarian hormones (2). It has also been speculated that physiological levels of female hormones act peripherally to raise carotid body chemosensitivity (60), although the combined administration of estrogen and progestin is a more effective stimulus for increased ventilation (15,59). To evaluate whether E2-␤ administration stimulated ventilatory responses in our experiments, arterial PO 2 , PCO 2 , and pH were measured in vehicle-and estrogen-treated animals at the end of each experiment (see Table 1).…”

Section: Discussionmentioning

confidence: 99%

17β-Estradiol decreases hypoxic induction of erythropoietin gene expression

Mukundan

Resta

Kanagy

2002

American Journal of Physiology-Regulatory, Integrative and Comp

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Mukundan, Harshini, Thomas C. Resta, and Nancy L. Kanagy. 17␤-Estradiol decreases hypoxic induction of erythropoietin gene expression. Am J Physiol Regulatory Integrative Comp Physiol 283: R496-R504, 2002. First published April 4, 2002 10.1152/ajpregu.00573.2001.-Exposure to chronic hypoxia induces erythropoietin (EPO) production to facilitate oxygen delivery to hypoxic tissues. Previous studies from our laboratory found that ovariectomy (OVX) exacerbates the polycythemic response to hypoxia and treatment with 17␤-estradiol (E2-␤) inhibits this effect. We hypothesized that E2-␤ decreases EPO gene expression during hypoxia. Because E2-␤ can induce nitric oxide (NO) production and NO can attenuate EPO synthesis, we further hypothesized that E2-␤ inhibition of EPO gene expression is mediated by NO. These hypotheses were tested in OVX catheterized rats treated with E2-␤ (20 g/day) or vehicle for 14 days and exposed to 8 or 12 h of hypoxia (12% O 2) or normoxia. We found that E2-␤ treatment significantly decreased EPO synthesis and gene expression during hypoxia. E2-␤ treatment did not induce endothelial NO synthase (eNOS) expression in the kidney but potentiated hypoxiainduced increases in plasma nitrates. We conclude that E2-␤ decreases hypoxic induction of EPO. However, this effect does not appear to be related to changes in renal eNOS expression. nitric oxide; polycythemia; hypoxia CHRONIC EXPOSURE TO HYPOXIA can cause a number of pathophysiological conditions including pulmonary hypertension and chronic mountain sickness. Hypoxic induction of erythropoiesis leads to polycythemia, which may contribute to the development of these diseases. Erythropoiesis is mediated by the small glycoprotein hormone erythropoietin (EPO; Refs. 3, 12). In adults, EPO is primarily synthesized in the kidney and stimulates red blood cell synthesis in bone marrow. During hypoxia, elevated red blood cell numbers help to compensate for compromised oxygen delivery to tissues.The physiological and biochemical properties of EPO have been extensively studied, but there are few studies to investigate gender differences in regulation of the hormone. It has been demonstrated that 17␤-estradiol (E2-␤) can influence the expression of hypoxiainducible genes such as vascular endothelial growth factor and endothelin-1 (ET-1) (4, 11, 58). However, estrogen regulation of EPO gene expression is not well understood. In some tissues such as the uterus and ovaries, E2-␤ has been shown to induce EPO production (34, 67). However, this regulation seems to be independent of pathways involved in hypoxic stimulation of EPO synthesis. In contrast, several investigators have shown that women living at high altitude have a lower hematocrit compared with men at the same altitude. Peschle et al. (40) observed that administration of estrogen benzoate (10 g/day) to ovariectomized (OVX) rats attenuated increases in plasma iron following hypoxia. Studies from our laboratory (46) have also shown that OVX augments hypoxia-induced increases in hematocrit in rats (0.5 atm, ...

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“…La testosterona no solo tiene un efecto estimulador de la eritropoyesis sino también inhibe la ventilación (28) , mientras que el estradiol inhibe la eritropoyesis y estimula la ventilación (29,30) . En ese sentido, un incremento en los niveles de estrógenos circulantes se asocia con mayores valores de saturación arterial de oxígeno (31) .…”

Section: Hormonas Y Adaptación a La Alturaunclassified

Hemoglobina y testosterona: importancia en la aclimatación y adaptación a la altura

Gonzales

2011

Rev Peru Med Exp Salud Publica

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RESUMENLos diferentes tipos de mecanismos que emplea el organismo cuando se enfrenta a una situación de hipoxia incluyen la acomodación, la aclimatación y la adaptación. La acomodación es la respuesta inicial a la exposición aguda a la hipoxia de altura y se caracteriza por aumento de la ventilación y de la frecuencia cardiaca. La aclimatación se presenta en los individuos que están temporalmente expuestos a la altura y, que en cierto grado, les permite tolerar la altura. En esta fase hay un incremento en la eritropoyesis, se incrementa la concentración de hemoglobina y mejora la capacidad de transporte de oxígeno. La adaptación es el proceso de aclimatación natural donde entra en juego las variaciones genéticas y la aclimatación que les permiten a los individuos vivir sin dificultad en la altura. La testosterona es una hormona que regula la eritropoyesis y la ventilación, podría estar asociada con los procesos de aclimatación y adaptación a la altura. La eritrocitosis excesiva que conduce al mal de montaña crónico es causada por una baja saturación arterial de oxígeno, una ineficiencia ventilatoria y reducida respuesta ventilatoria a la hipoxia. La testosterona se incrementa en la exposición aguda en la altura y en los nativos de altura con eritrocitosis excesiva. Los resultados de las investigaciones actuales permitirían concluir que el incremento de la testosterona y de la hemoglobina son buenas para la aclimatación adquirida pues mejoran el transporte de oxígeno pero no para la adaptación a la altura, dado que valores altos de testosterona en suero se asocian con eritrocitosis excesiva.Palabras clave: Testosterona, Eritropoyesis, Altitud, Aclimatación, Adaptación Fisiológica (fuente: DeCS BIREME). HEMOGLOBIN AND TESTOSTERONE: IMPORTANCE ON HIGH ALTITUDE ACCLIMATIZATION AND ADAPTATION ABSTRACTThe different types of response mechanisms that the organism uses when exposed to hypoxia include accommodation, acclimatization and adaptation. Accommodation is the initial response to acute exposure to high altitude hypoxia and is characterized by an increase in ventilation and heart rate. Acclimatization is observed in individuals temporarily exposed to high altitude, and to some extent, it enables them to tolerate the high altitudes. In this phase, erythropoiesis is increased, resulting in higher hemoglobin and hematocrit levels to improve oxygen delivery capacity. Adaptation is the process of natural acclimatization where genetical variations and acclimatization play a role in allowing subjects to live without any difficulties at high altitudes. Testosterone is a hormone that regulates erythropoiesis and ventilation and could be associated to the processes of acclimatization and adaptation to high altitude. Excessive erythrocytosis, which leads to chronic mountain sickness, is caused by low arterial oxygen saturation, ventilatory inefficiency and reduced ventilatory response to hypoxia. Testosterone increases during acute exposure to high altitude and also in natives at high altitude with excessive erythrocytosis. R...

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Differential effects of ventilatory stimulation by sex hormones and almitrine on hypoxic erythrocytosis

Cited by 17 publications

References 26 publications

High serum zinc and serum testosterone levels were associated with excessive erythrocytosis in men at high altitudes

High serum zinc and serum testosterone levels were associated with excessive erythrocytosis in men at high altitudes

17β-Estradiol decreases hypoxic induction of erythropoietin gene expression

Hemoglobina y testosterona: importancia en la aclimatación y adaptación a la altura

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