title: Generation of growth hormone pulsatility in women: evidence against somatostatin withdrawal as pulse initiator.
abstract: To test whether endogenous hypothalamic somatostatin (SRIH) fluctuations are playing a role in the generation of growth hormone (GH) pulses, continuous subcutaneous octreotide infusion (16 microg/h) was used to create constant supraphysiological somatostatinergic tone. Six healthy postmenopausal women (age 67 +/- 3 yr, body mass index 24.7 +/- 1.2 kg/m(2)) were studied during normal saline and octreotide infusion providing stable plasma octreotide levels of 2,567 +/- 37 pg/ml. Blood samples were obtained every 10 min for 24 h, and plasma GH was measured with a sensitive chemiluminometric assay. Octreotide infusion suppressed 24-h mean GH by 84 +/- 3% (P = 0.00026), GH pulse amplitude by 90 +/- 3% (P = 0.00031), and trough GH by 54 +/- 5% (P = 0.0012), whereas GH pulse frequency remained unchanged. The response of GH to GH-releasing hormone (GHRH) was not suppressed, and the GH response to GH-releasing peptide-6 (GHRP-6) was unaffected. We conclude that, in women, periodic declines in hypothalamic SRIH secretion are not the driving force of endogenous GH pulses, which are most likely due to episodic release of GHRH and/or the endogenous GHRP-like ligand.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Michigan and Veterans Affairs Medical Center, Ann Arbor, MI 48109, USA.
authors.forename: E V
authors.initials: EV
authors.lastname: Dimaraki
authors.forename: C A
authors.initials: CA
authors.lastname: Jaffe
authors.forename: R
authors.initials: R
authors.lastname: Demott-Friberg
authors.forename: M
authors.initials: M
authors.lastname: Russell-Aulet
authors.forename: C Y
authors.initials: CY
authors.lastname: Bowers
authors.forename: P
authors.initials: P
authors.lastname: Marbach
authors.forename: A L
authors.initials: AL
authors.lastname: Barkan
mesh_terms: D000368:Aged; D015992:Body Mass Index; D005260:Female; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology; D006728:Hormones / Q000008:administration & dosage / Q000097:blood; D019382:Human Growth Hormone / Q000378:metabolism*; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism; D008163:Luminescent Measurements; D008875:Middle Aged; D015282:Octreotide / Q000008:administration & dosage / Q000097:blood; D009842:Oligopeptides / Q000494:pharmacology; D010507:Periodicity; D017698:Postmenopause; D013004:Somatostatin / Q000378:metabolism*; D013972:Thyrotropin / Q000097:blood; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology
chemical_list: D006728:Hormones; D009842:Oligopeptides; D019382:Human Growth Hormone; C041048:growth hormone releasing hexapeptide; D013004:Somatostatin; D013973:Thyrotropin-Releasing Hormone; D013972:Thyrotropin; D013007:Growth Hormone-Releasing Hormone; D015282:Octreotide