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Peptidomimetic Regulation of Growth Hormone Secretion

Merck Research Laboratories, Rahway, New Jersey 07065

I. Introduction

II. Identification of Peptidomimetic GH Secretagogues

A. Mechanism of action of GHRH, GHRP-6, and somatostatin

B. In vitro assays

III. Molecular Design by Medicinal Chemistry

A. Benzolactams and L-692,429

B. Spiroindanes and MK-0677

C. Isonipecotic acid peptidomimetics

IV. Characterization of the MK-0677 Receptor

A. Pituitary gland

B. Hypothalamus

V. Signal Transduction Pathway

VI. Cloning the GH Secretagogue Receptor

A. Chromosomal localization

VII. Action of the Peptidomimetic GH Secretagogues in the Central Nervous System

VIII. Peptidomimetic GH Secretagogues in Vivo

A. Animal models

B. Clinical studies in humans

IX. Regulation of Pulsatile GH Release

A. GHRH and somatostatin

B. The role of GHS-R

X. Concluding Comments