Endocrine responses to acute and chronic high-altitude exposure (4,300 meters): modulating effects of caloric restriction

Abstract

High-altitude anorexia leads to a hormonal response pattern modulated by both hypoxia and caloric restriction (CR). The purpose of this study was to compare altitude-induced neuroendocrine changes with or without energy imbalance and to explore how energy sufficiency alters the endocrine acclimatization process. Twenty-six normal-weight, young men were studied for 3 wk. One group [hypocaloric group (HYPO), n = 9] stayed at sea level and consumed 40% fewer calories than required to maintain body weight. Two other groups were deployed to 4,300 meters (Pikes Peak, CO), where one group (ADQ, n = 7) was adequately fed to maintain body weight and the other [deficient group (DEF), n = 10] had calories restricted as above. HYPO experienced a typical CR-induced reduction in many hormones such as insulin, testosterone, and leptin. At altitude, fasting glucose, insulin, and epinephrine exhibited a muted rise in DEF compared with ADQ. Free thyroxine, thyroid-stimulating hormone, and norepinephrine showed similar patterns between the two altitude groups. Morning cortisol initially rose higher in DEF than ADQ at 4,300 meters, but the difference disappeared by day 5. Testosterone increased in both altitude groups acutely but declined over time in DEF only. Adiponectin and leptin did not change significantly from sea level baseline values in either altitude group regardless of energy intake. These data suggest that hypoxia tends to increase blood hormone concentrations, but anorexia suppresses elements of the endocrine response. Such suppression results in the preservation of energy stores but may sacrifice the facilitation of oxygen delivery and the use of oxygen-efficient fuels.

Endocrine and metabolic responses to extreme altitude and physical exercise in climbers

“…Everest climbing (14) reported an increase in total T 4 and T 3 concentration associated with an increase in TSH levels. On the other hand, significant elevation of free T 4 levels after 3 weeks at 4300 m without any change in TSH levels have been reported (20). Our present findings recorded after a 2-month stay at HA confirm the lack of change in TSH levels as well as the increase in fT 4 levels, while they show significant reduction of fT 3 levels that were below the lowest limit of the normal range.…”

“…More recently, the emerging role of leptin and ghrelin in the regulation of energy balance prompted an evaluation of leptin response to HA (17)(18)(19)(20). Subjects exposed to HA lose significant amounts of body mass from fat mass as well as fat-free mass, particularly if involved in physical performance such as climbing (10,11).…”

“…In this context, significant variations in leptin and ghrelin secretion were expected but the data available so far are discrepant. Leptin levels have been reported as either increased (17,19), decreased (18), or unchanged (20), while a trend towards decreased ghrelin levels has been reported at HA (19).…”

Serum testosterone levels and excessive erythrocytosis during the process of adaptation to high altitudes

“…Similarly, serum testosterone levels increase in men and male rats exposed to acute hypoxia. 15,[90][91][92] Because testosterone is a hypoventilatory hormone, we have suggested that an increase in serum testosterone is related to a negative feedback mechanism of hyperventilation to avoid an exaggerated response of the organism that could result in respiratory alkalosis and symptoms. 15 An increase in serum testosterone may also enhance erythropoiesis, supporting acclimatisation.…”

Adaptation of ghrelin and the GH/IGF axis to high altitude

“…Published data have been somewhat inconsistent reporting an increase (12,37), a decrease (38), or no change (13,39) in leptin after ascent to HA. However, hypoxia has been shown to clearly increase leptin gene expression in adipocyte studies (40).…”