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1 Divisions of Endocrinology and Metabolism and 3 Gastroenterology, University of Michigan Medical Center, and 2 Department of Veterans Affairs Medical Center, Ann Arbor, Michigan 48109; and 4 Department of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599
The importance of gender-specific
growth hormone (GH) secretion pattern in the regulation of growth and
metabolism has been demonstrated clearly in rodents. We recently showed
that GH secretion in humans is also sexually dimorphic. Whether GH
secretion pattern regulates the metabolic effects of GH in humans is
largely unknown. To address this question, we administered the same
daily intravenous dose of GH (0.5 mg · m
2 · day1)
for 8 days in different patterns to nine GH-deficient adults. Each
subject was studied on four occasions: protocol 1 (no
treatment), protocol 2 (80% daily dose at 0100 and 10%
daily dose at 0900 and 1700), protocol 3 (8 equal boluses
every 3 h), and protocol 4 (continuous GH infusion).
The effects of GH pattern on serum IGF-I, IGF-binding protein
(IGFBP)-3, osteocalcin, and urine deoxypyridinoline were measured.
Hepatic CYP1A2 and CYP3A4 activities were assessed by the caffeine and
erythromycin breath tests, respectively. Protocols 3 and
4 were the most effective in increasing serum IGF-I and IGFBP-3, whereas protocols administering pulsatile GH had the greatest
effects on markers of bone formation and resorption. All GH treatments
decreased CYP1A2 activity, and the effect was greatest for pulsatile
GH. Pulsatile GH decreased, whereas continuous GH infusion increased,
CYP3A4 activity. These data demonstrate that GH pulse pattern is an
independent parameter of GH action in humans. Gender differences in
drug metabolism and, potentially, gender differences in growth rate may
be explained by sex-specific GH secretion patterns.
sex characteristics; insulin-like growth factor I; bone; cytochrome P-450
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