This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hanew, K. Articles by Yokogoshi, Y. Search for Related Content PubMed PubMed Citation Articles by Hanew, K. Articles by Yokogoshi, Y.

Secretory Mechanisms of Growth Hormone (GH)-Releasing Peptide-, GH-Releasing Hormone-, and Thyrotropin-Releasing Hormone-Induced GH Release in Patients with Acromegaly

Hanew Endocrine Clinic (K.H.), Second Department of Internal Medicine (K.H., A.U., A.T.), and the Department of Neurosurgery (H.I.), Tohoku University School of Medicine, Sendai 980; and the First Department of Internal Medicine, Tokushima University School of Medicine (H.Y.), Tokushima 770, Japan

Address all correspondence and requests for reprints to: Kunihiko Hanew, M.D., Hanew Endocrine Clinic, 2–5 Hasekurachou, Aobaku, Sendai 980, Japan.

The GH secretory mechanism of GH-releasing hexapeptide (GHRP-6), GHRH, and TRH were studied in vivo and in vitro in seven patients with acromegaly. In an in vivo study, these patients showed clear GH responses to single administration of GHRP (four of four patients), GHRH (seven of seven patients), and TRH (seven of seven patients) and enhanced responses to GHRP plus GHRH (two of four patients) or TRH plus GHRH (six of six patients). In an in vitro dispersed cell study, the majority of patients examined also showed clear GH responses to GHRP (four of four patients), GHRH (six of six patients), and TRH (four of four patients) and an enhanced response to GHRP plus GHRH (three of three patients) or TRH plus GHRH (three of four patients). In one patient (no. 3), GHRP plus forskolin (adenylate cyclase activator), but not GHRP plus phorbol 12-myristate 13-acetate (protein kinase C activator), additively enhanced the GH response. Nordihydroguaiaretic acid (NDGA; inhibitor of arachidonic cascade) inhibited GH release induced by GHRP, TRH, GHRH, TRH plus GHRH, or GHRP plus GHRH, but did not inhibit basal GH secretion. In contrast, NDGA distinctly elevated intracellular cAMP levels in another patient (no. 7) when coadministered with GHRP, GHRH, or GHRP plus GHRH, whereas cAMP levels were not modified by single administration of GHRP and NDGA. The GH response to the combined administration of GHRP and GHRH was synergistic in this patient, but was additive in the other two patients.

It is concluded that GHRP, TRH, and GHRH directly stimulate in vivo and in vitro GH release from human somatotropinomas, and GHRP and TRH mainly exert their action through activation of the phosphatidylinositol-protein kinase C pathway, whereas GHRH exerts its action through the adenylate cyclase-protein kinase A pathway. These three agents seem to release GH via the arachidonic cascade.

This article has been cited by other articles:

				R. D. Kineman and R. M. Luque Evidence that Ghrelin Is as Potent as Growth Hormone (GH)-Releasing Hormone (GHRH) in Releasing GH from Primary Pituitary Cell Cultures of a Nonhuman Primate (Papio anubis), Acting through Intracellular Signaling Pathways Distinct from GHRH Endocrinology, September 1, 2007; 148(9): 4440 - 4449. [Abstract] [Full Text] [PDF]