Disturbances of growth hormone-insulin-like growth factor axis and response to growth hormone in acidosis.
Severe chronic metabolic acidosis (CMA) in rats is associated with poor food intake and downregulation of growth hormone (GH), insulin-like growth factors (IGFs), and liver receptors; the administration of recombinant GH (rGH) fails to improve the growth failure. In mice with carbonic anhydrase II deficiency (CAD), a model of moderate CMA with food intake close to normal, we studied serum levels of GH, IGFs, and IGF-binding proteins, and the growth response to rGH. CAD was associated with low serum levels of GH in males. Randomized administration of rGH from approximately 5 to approximately 12 wk to CAD mice improved food efficiency and increased serum IGF-I levels, final length, and weight compared with placebo without affecting blood pH. Although administration of rGH also increased linear growth in healthy animals, the effect was less than that in CAD mice and was only observed when started before 6 wk of life. Thus growth failure in CAD mice is associated with a decrease in GH secretion in males but not in females. Long-term administration of rGH increases linear growth in CAD mice despite persistent CMA.
Department of Pediatrics, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York 10461, USA.
K
K
Jandziszak
C
C
Suarez
E
E
Wasserman
R
R
Clark
B
B
Baker
F
F
Liu
R
R
Hintz
P
P
Saenger
L P
LP
Brion
D000138:Acidosis / Q000503:physiopathology*; D000818:Animals; D002256:Carbonic Anhydrases / Q000172:deficiency*; D002940:Circadian Rhythm; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D002149:Energy Intake; D005260:Female; D006128:Growth / Q000502:physiology; D013006:Growth Hormone / Q000097:blood* / Q000494:pharmacology*; D006579:Heterozygote; D006706:Homeostasis; D006720:Homozygote; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000097:blood; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000097:blood; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D012727:Sex Characteristics
D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D018974:Insulin-Like Growth Factor Binding Protein 4; D018969:Insulin-Like Growth Factor Binding Proteins; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D013006:Growth Hormone; D002256:Carbonic Anhydrases