Effect of growth hormone therapy in mitigating hypoxia-induced and food restriction-induced growth retardation in the newborn rat.
OBJECTIVE
Hypoxia may alter the neuroendocrine control of catabolic and anabolic states early in postnatal life by modulating the growth hormone-insulin-like growth factor-I (GH-IGF-I) system. We wondered: a) to what extent hypoxia effects on the GH-IGF-I axis differed from those of food deprivation alone; and b) whether administration of exogenous GH mitigates alterations of the GH-IGF-I axis caused by hypoxia or food restriction.


METHODS
Prospective laboratory investigation using nursing dams and suckling pups. Experimental groups included: a) room air control subjects; b) hypoxia-exposed subjects (FIO2, 0.12); or c) room air breathing subjects whose dam food intake was matched to that of hypoxic dams. Half of the pups in each group were administered rat GH (100 microg subcutaneously each day), and the remaining received vehicle alone. The intervention lasted 18 days.


METHODS
Research laboratory in a university medical center.


METHODS
Twelve litters of 1-day-old Sprague-Dawley rat pups and nursing dams.


METHODS
Hypoxia exposure, food restriction, GH administration.


RESULTS
By the end of the study, body weights of the hypoxic and pair-fed pups were significantly lower than the weights of control animals (p < .001 for both groups), and weight gain correlated significantly with total dam food consumption (r2 = .85, p < .0001). GH administration increased weight gain only in hypoxic animals (p < .001) but it increased tail lengths significantly in both hypoxic and control pups (p < .001). Serum IGF-I levels in both hypoxic and pair-fed pups were significantly lower than in control animals. Serum IGF-binding protein-3 (IGFBP-3) was significantly lower in the hypoxic compared with the control animals. GH administration resulted in significant increases in serum levels of IGFBP-3 in both the control (p < .05) and the hypoxic (p < .01) pups compared with their vehicle-treated litter mates.


CONCLUSIONS
Exogenous GH attenuates growth impairment associated with hypoxia but not with food restriction, and these effects may be mediated in part by IGFBP-3.
Moromisato
D Y
DY
Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA, USA.
Moromisato
M Y
MY
Brasel
J A
JA
Cooper
D M
DM
D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development*; D001835:Body Weight; D004195:Disease Models, Animal; D005183:Failure to Thrive / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D005260:Female; D005508:Food Deprivation; D013006:Growth Hormone / Q000008:administration & dosage / Q000627:therapeutic use*; D000860:Hypoxia / Q000150:complications*; D007279:Injections, Subcutaneous; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D018811:Maternal Exposure / Q000009:adverse effects*; D011446:Prospective Studies; D051381:Rats; D017207:Rats, Sprague-Dawley / Q000254:growth & development; D016896:Treatment Outcome
D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone