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1 Department of Internal Medicine, Division of Endocrinology and Metabolism, University of Michigan, Ann Arbor, Michigan, USA
2 Department of Internal Medicine, Division of Endocrinology and Metabolism, University of Michigan, Ann Arbor, Michigan, USA; Department of Veterans Affairs Medical Center, Ann Arbor, Michigan, USA
3 Department of Internal Medicine, Division of Endocrinology and Metabolism, Tulane University, New Orleans, Louisiana, USA
4 Novartis Pharma Ltd., Basle, Switzerland
* To whom correspondence should be addressed. E-mail: abarkan{at}umich.edu.
Using a continuous subcutaneous octreotide infusion to create constant supraphysiologic somatostatinergic tone, we have previously shown that GH pulse generation in women is independent of endogenous SRIH declines. Generalization of these results to men is problematic because GH regulation is sexually dimorphic. We have therefore studied nine healthy young men (age 26±6 years, BMI 23.3±1.2 kg/m2) during normal saline and octreotide infusion (8.4 µg/h) that provided stable plasma octreotide levels (764.5±11.6 pg/ml). GH was measured in blood samples obtained every 10 min for 24h. Octreotide suppressed 24-h mean GH by 52±13% (P=0.016), GH pulse amplitude by 47±12% (P=0.012), and trough GH by 39±12% (P=0.030), whereas GH pulse frequency and the diurnal rhythm of GH secretion remained essentially unchanged. The response of GH to GH-releasing hormone (GHRH) was suppressed by 38±15% (P=0.012), but the GH response to GH-releasing peptide-2 (GHRP-2) was unaffected. We conclude that like in women, in men, declines in hypothalamic SRIH secretion are not required for pulse generation and are not the cause of the nocturnal augmentation of GH secretion. We propose that GH pulses are primarily driven by GHRH whereas ghrelin might be responsible for the diurnal rhythm of GH.
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