Diurnal Variation in the Responsiveness of Human Subjects to Human Growth Hormone

Abstract

A B S T R A C T 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)"'4 per day; B, 0.0532 U/kg BW"/' per day; C, 0.168 U/kg BW"'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. ACTHdeficient 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.

Responsiveness of Growth Hormone-Deficient Children to Human Growth Hormone EFFECT OF REPLACEMENT THERAPY FOR ONE YEAR

“…Further experiments at various times during the year will be neces- 2 During the control period of exps. 1 and 3, the elemental balances were zero or slightly positive (Fig.…”

Pharmacological Aspects of Growth Hormone Replacement Therapy: Route, Frequency and Timing of Administration

“…Two independent studies [37,39] present evidence that the timing of GH administration is of significance. In both studies, evening injections were superior in terms of nitrogen retention [37] and metabolic homeo stasis [39], respectively.…”

“…3). Although such a relationship does not imply causality, it is likely that the pattern of high levels of lipid intermediates and low levels of gluconeogenic precursors normally observed during night and in other conditions of short-term fasting [40] reflects increased lipid oxidation and impeded gluconeogenesis, and there fore also a sparing of protein [40], Since this pattern is only seen in GH-treated patients following evening in jections, this could explain the observation by Rudman et al [37] of increased nitrogen retention after evening GH administration.…”

“…Whether this inherent secre tory pattern is important for the growth-promoting ef- Data are derived from Rudman et al [37], The GH dose was 0.064 U /kg-day'1, i.e. = 3 IU/day.…”

“…Rud man et al [37] evaluated the effects of time of GH administration on the metabolic response in a 7-day metabolic balance study in 7 GH-deficient children and 3 adults with muscular dystrophies. With a daily replace ment dose of 0.064 U/kg-day-1, a significantly higher increase in elemental balance of nitrogen was obtained when GH was administered in the evening (table 1).…”