Diurnal variation in the responsiveness of human subjects to human growth hormone.

The objective of this study was to compare the responsiveness of human subjects to the anabolic effects of human growth hormone (HGH) administered at 8 a.m. or at 11 p.m. Three doses of HGH were used: A, 0.0168 U/kg body weight (BW)(3/4) per day; B, 0.0532 U/kg BW(3/4) per day; C, 0.168 U/kg BW(3/4) per day. The effect of each dose on daily balances of N, P, Na, and K and on BW was measured. The subjects were of two groups: (a) seven GH-deficient children, of whom three were deficient in ACTH; and (b) three patients with limb-girdle dystrophy. ACTH-deficient patients in group (a) received exogenous cortisol at 7 a.m. In all 10 subjects, the anabolic effects of dose C, and sometimes of B and A, administered at 11 p.m. were significantly (P < 0.05) greater than when administered at 8 a.m. In these experiments plasma cortisol concentration averaged 3 times greater at 8 a.m. than at 11 p.m. In the next experiments, exogenous cortisol was administered to the three ACTH-deficient patients at 10 p.m. and the responsiveness to HGH injected at 11 p.m. vs. 8 a.m. was again compared. Under these conditions, when plasma cortisol concentration averaged 3 times greater at 11 p.m. than at 8 a.m., HGH injected at 8 a.m. caused significantly greater anabolic responses than HGH injected at 11 p.m. These findings indicate that the magnitude of the anabolic response to exogenous HGH is inversely related to the plasma cortisol concentration at the time of HGH injection.