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-pituitary function in men adapted to high altitude living using exogenous administration of synthetic hypothalamic hormones.


METHODS
Growth hormone releasing hormone (Geref 1-29) 1 microgram/kg, TRH 500 micrograms, GHRH 100 micrograms and ovine corticotrophin releasing hormone (oCRH) 1 microgram/kg were simultaneously administered intravenously to two groups of men: 12 born and raised in the city of Pasto, Colombia, South America, located at an altitude of 2600 m in the southern Colombian Andes (HA group) and 10 men living at sea level (SL) in Tampa, Florida.


METHODS
The following hormones were measured: GH, IGF-I, TSH, T4, free T4, free T3, PRL, ACTH, beta-endorphin and cortisol. IGF binding protein-3 (IGFBP-3) and cortisol binding globulin (CBG) were also measured.


RESULTS
GH response to GHRH in HA men was exaggerated compared to SL men, and IGF-I concentration was also significantly increased in the presence of normal levels of IGFBP-3. No differences in TSH or PRL responses were found following TRH. HA men had lower basal total T4 levels, but higher free T4 and free T3 concentrations. The basal ACTH concentrations in the HA men were significantly lower than SL, although the response to oCRH was still present. beta-Endorphin basal levels were similar at HA and SL but the response to oCRH at HA was blunted. At HA, basal cortisol 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 response to the administration of GHRH in HA men and also of a significant increase in IGF-I concentration in the same subjects in the presence of normal levels of IGFBP-3. An altered hypothalamic-pituitary response was found in HA men after administration of oCRH characterized by a significantly lower basal ACTH concentration at HA, although the response to oCRH was present but the beta-endorphin response to oCRH was blunted. At HA, basal cortisol levels, as well as CBG, were elevated and 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 HA men comparing their response to age/sex matched SL men.
Ramirez
G
G
Department of Internal Medicine, James A Haley VA Hospital, Tampa, Florida 33612, USA.
Herrera
R
R
Pineda
D
D
Bittle
P A
PA
Rabb
H A
HA
Bercu
B B
BB
D000222:Adaptation, Physiological; D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000328:Adult; D000531:Altitude; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D013006:Growth Hormone / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology; D006728:Hormones / Q000494:pharmacology; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D012636:Secretory Rate; D017337:Sermorelin / Q000494:pharmacology; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology; D013974:Thyroxine / Q000378:metabolism; D014284:Triiodothyronine / Q000378:metabolism
D006728:Hormones; D014284:Triiodothyronine; D013973:Thyrotropin-Releasing Hormone; D007334:Insulin-Like Growth Factor I; D017337:Sermorelin; D000324:Adrenocorticotropic Hormone; D013006:Growth Hormone; D003346:Corticotropin-Releasing Hormone; D013007:Growth Hormone-Releasing Hormone; D013974:Thyroxine; D006854:Hydrocortisone