THE EFFECTS OF HIGH-ALTITUDE ON HYPOTHALAMIC-PITUITARY SECRETORY DYNAMICS IN MEN

OBJECTIVE Individuals adapted to high altitude (HA) have abnormalities in endocrine function and specifically In the pituitary-thyroid axis and aldosterone regulation. In this study we assessed hypothalamic-pit uitary function in men adapted to high altitude living using exogenous administration of synthetic hypothalamic hormones. DESIGN Growth horm one releasing hormone (Geref 1-29) 1 mu g/kg, TRH 500 mu g, GHRH 100 m u g and ovine corticotrophin releasing hormone (oCRH) 1 mu g/kg were s imultaneously administered intravenously to two groups of men: 12 born and raised in the city of Paste, Colombia, South America, located at an altitude of 2600 m in the southern Colombian Andes (HA group) and 1 0 men living at sea level (SL) in Tampa, Florida. MEASUREMENTS The fol lowing hormones were measured: GH, IGF-I, TSH, T4, free T4, free T3, P RL, ACTH, beta-endorphin and cortisol. IGF binding protein-3 (IGFBP-3) and cortisol binding globulin (CBG) were also measured. RESULTS GH re sponse to GHRH in HA men was exaggerated compared to SL men, and IGF-I concentration was also significantly increased in the presence of nor mal levers of IGFBP-3. No differences in TSH or PRL responses were fou nd following TRH. HA men had lower basal total T4 levels, but higher f ree T4 and free T3 concentrations. The basal ACTH concentrations in th e HA men were significantly lower than SL, although the response to oC RH was still present. beta-Endorphin basal levels were similar at HA a nd SL but the response to oCRH at HA was blunted. At HA, basal cortiso l levels as well as CBG were elevated compared to SL and, In contrast to SL, did not increase significantly after endogenous ACTH secretion. CONCLUSIONS This study is the first description of exaggerated GH res ponse to the administration of GHRH in HA men and also of a significan t increase in IGF-I concentration in the same subjects in the presence of normal levels of IGFBP-3. An altered hypothalamic-pituitary respon se was found in HA men after administration of oCRH characterized by a significantly lower basal ACTH concentration at HA, although the resp onse to oCRH was present but the beta-endorphin response to oCRH was b lunted. At HA, basal cortisol levels, as well as CBG, were elevated an d the cortisol levels did not significantly increase after endogenous ACTH secretion. We have characterized the differences in hypothalamic- pituitary dynamics after the administration of TRH, GnRH and oCRH in H A men comparing their response to age/sex sex matched SL men.