Growth hormone (GH) secretion, GH-dependent gene expression, and sexually dimorphic body growth in young rats with chronic renal failure.
Chronic renal disease results in growth failure in children. This study sought to determine the influences of early renal failure on body growth, growth hormone (GH) secretion, and GH-dependent hepatic gene expression. Neonatal animals were subjected to five-sixth nephrectomy (Nephr) and monitored during growth. Sham-operated male (Sham) and female (Fem) rats served as controls. Whereas Nephr of adult animals causes renal insufficiency, neonatal nephrectomy leads to frank renal failure. In male Nephr compared with Sham animals, GH half-life and GH pulse frequency increased by 1.55- and 1.33-fold, respectively, and GH secretory-burst size decreased by 80%. Approximate entropy analysis quantified more disorderly patterns of GH secretion in Nephr animals, which differed from Sham males, but not from Fem rats. Expression of liver P450 CYP2C11 mRNA, which is dependent upon the male GH pattern, became undetectable, whereas expression of liver P450 CYP2C12 mRNA, which is dependent upon the female GH pattern, increased multifold. Renal failure in young rats abrogates the male pattern of GH pulsatility, abolishes the sexual dimorphism of body weight gain, and induces a female pattern of hepatic gene expression. These data raise the possibility that disruption of pulsatile GH secretion contributes to the growth failure of renal disease.
Krieg
Richard J
RJ
Department of Anatomy and Neurobiology, Medical College of Virginia Campus, Virginia Commonwealth University, P.O. Box 980709, Richmond, VA 23298-0709, USA. krieg@vcu.edu
Veldhuis
Johannes D
JD
Thornhill
Barbara A
BA
Chevalier
Robert L
RL
Gil
Gregorio
G
D000818:Animals; D000831:Animals, Newborn; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D001806:Blood Urea Nitrogen; D001835:Body Weight; D003404:Creatinine / Q000097:blood; D000072467:Cytochrome P450 Family 2; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D006130:Growth Disorders / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D013006:Growth Hormone / Q000097:blood / Q000378:metabolism*; D007676:Kidney Failure, Chronic / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D009392:Nephrectomy; D011247:Pregnancy; D051381:Rats; D012727:Sex Characteristics; D039181:Steroid 16-alpha-Hydroxylase / Q000235:genetics*
D013006:Growth Hormone; D003404:Creatinine; D001189:Aryl Hydrocarbon Hydroxylases; C450279:CYP2C11 protein, rat; D000072467:Cytochrome P450 Family 2; D039181:Steroid 16-alpha-Hydroxylase