Growth hormone (GH) is secreted from the pituitary gland in pulses under the influence of several hypothalamic factors, the most important being GH-releasing hormone (GHRH), which stimulates GH secretion, and somatostatin (SRIH), which inhibits GH secretion. It has been suggested that GH pulses are due to GHRH pulses, periodic declines of SRIH, or an interaction of these two factors. Our hypothesis is that SRIH declines are not the principal cause of the GH pulses. To test this hypothesis the long-acting SRIH analog octreotide is administered as a continuous subcutaneous (s.c.) infusion with the goal to obscure the effects of any endogenous SRIH fluctuations. Our results from a similar study in older women supports our hypothesis. Since the regulation of GH secretion is sexually dimorphic we are examining the same hypothesis in men. We will study 10 healthy men, 18-40 years old, for three days, twice, once during normal saline (NS) s.c. infusion and once during octreotide infusion. An intravenous (i.v.) catheter will be placed in an arm vein for the purpose of collecting blood samples and medication injection. An infusion pump (similar to the insulin pumps) will be used for the s.c. infusion and a small needle will be inserted in the skin of the abdomen. The infusion will be started at 2200h of the first day and will be continued without interruption until 1300h on the third day. From 0600h on the second day until 1330h on the third day a small amount of blood (0.8 cc) will be drawn through the i.v. catheter every 10 minutes to measure GH. Additional samples will be drawn for octreotide levels and TSH levels. On the third day, three i.v. injections of GHRH, TRH and GHRP will be given. TRH is a synthetic peptide that releases thyroid stimulating hormone (TSH) from the pituitary gland. It is approved for clinical use. GHRH and GHRP are both synthetic peptides that are approved for investigational use, and they both stimulate release of GH from the pituitary gland. The parameters of spontaneous GH secretion (mean GH level, GH pulse frequency), the response of GH to GHRH and GHRP and the response of TSH to TRH will be compared during NS and octreotide infusion. If the GH pulse frequency is not affected by the octreotide infusion, then factors other than SRIH declines are responsible for the occurrence of the pulses.

Project Start
1998-12-01
Project End
1999-11-30
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
39
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Type
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
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