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Articles in PresS, published online ahead of print July 16, 2002
Am J Physiol Endocrinol Metab, 10.1152/ajpendo.00513.2001
Submitted on November 13, 2001
Accepted on July 5, 2002
1 Division of Endocrinology and Metabolism, University of Michigan Medical Center, Ann Arbor, MI, USA; Department of Veterans Affairs Medical Center, University of Michigan Medical Center, Ann Arbor, MI, USA
2 Division of Gastroenterology, University of Michigan Medical Center, Ann Arbor, MI, USA
3 Division of Gastroenterology, University of Michigan Medical Center, Ann Arbor, MI, USA; Department of Veterans Affairs Medical Cetner, University of Michigan Medical Center, Ann Arbor, MI, USA
4 Department of Veterans Affairs Medical Center, University of Michigan Medical Center, Ann Arbor, MI, USA
5 Department of Medicine, University of North Carolina, Chapel Hill, NC, USA
* To whom correspondence should be addressed. E-mail: cjaffe{at}umich.edu.
The importance of gender-specific GH secretion pattern in the regulation of growth and metabolism has been clearly demonstrated 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. In order to address this question we administered the same daily intravenous dose of GH (0.5 mg/m2/d) for 8 days in different patterns to 9 GH-deficient adults. Each subject was studied on four occasions: Protocol 1 (no treatment); Protocol 2 (80% of daily dose at 0100 h and 10% daily dose at 0900 and 1700 h); Protocol 3 (8 equal boluses every 3 h); Protocol 4 (continuous GH infusion). The effects of GH pattern on serum IGF-I, 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.
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