ATTENUATED EFFECT OF GROWTH HORMONE(GH) IN ACIDOSIS- AND METHYLPREDNISONE(MP)-INDUCED GROWTH RETARDATION(GR) IN WEANLING RATS

Abstract

Acidosis and glucocorticoid excess retard linear growth. GH reverses MP-induced GR and stimulates urinary net acid excretion in mid-sized uremic rats. However, the efficacy of GH in reversing acidosis- and MP-induced GR in early postnatal life is unknown. We gave GH (0.5mg.s.c. 5d/wk × 2wk) to NH4Cl-treated(0.28M), MP-treated (6mg/kg/day), and control(H2O) weanling Sprague-Dawley rats (mean wt. 50gm) and to adult (A)(mean wt: 250gm) NH4CL-treated and control rats. Acidosis was confirmed by a mean venous pH of 7.26±.03 in NH4CL animals. Pair feeding (PF), matching food intake to NH4CL rats, was examined in a subset of weanling-and A-H2O rats. Compared with non-PF weanling H2O rats, who had change in length (d-It[cm]) of 5.68±0.07, linear growth was retarded (p<0.05) by NH4CL (d-lt 4.32±0.8), MP (d-lt 4.62±0.1), and PF (d-lt 4.63±0.05). PF markedly reduced weight gain (d-wt[gm]) in H2O rats (38±4 PF vs. 91±12 non-PF). In A rats, NH4CL diminished d-lt (2.64±0.25 vs. [A-H2O] 3.17±0.2) but PF did not. GH treatment did not accelerate growth in weanling NH4CL, MP, or H2O rats. In contrast, GH did increase d-lt in A-NH4CL rats (2.65±0.25 vs. 2.12±0.1; p<0.05). We conclude: 1) GH ameliorates acidosis-induced GR in A rats; 2) poor caloric intake accounts for much of acidosis-induced GR in weanling rats; 3) the efficacy of GH in reversing GR in acidosis- or MP-induced GR is limited in very young animals. These results suggest that rapid early linear growth in weanling rats is not primarily GH-dependent, and that neonatal GR due to acidosis or glucocorticoid excess results predominantly from mechanisms other than impaired GH secretion and action.