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Growth Hormone-Releasing Hormone Neurons in the Arcuate Nucleus Express Both Sst1 and Sst2 Somatostatin Receptor Genes

Departments of Pediatrics (G.S.T., W.-H.Z., M.L.) and Neurology and Neurosurgery (G.S.T., A.B.), McGill University, Montreal, Quebec H3H 1P3, Canada; and University of Colorado Health Science Center (P.Z.), Denver, Colorado 80218

Address all correspondence and requests for reprints to: Gloria S. Tannenbaum, Montreal Children’s Hospital Research Institute, Room 227, 4060 St. Catherine Street, West, Montreal H3Z 2Z3, Canada.

Several lines of evidence suggest that somatostatin (SRIF) regulates GH release through central control of hypothalamic GHRH neurons. A possible mechanism is through interaction with SRIF binding sites previously shown to be associated with a subpopulation of GHRH-containing neurons in the arcuate nucleus (Arc), although the molecular identity of these binding sites is not yet known. We performed dual chromogenic and autoradiographic in situ hybridization to determine whether GHRH neurons coexpress either the sst1 and/or sst2 SRIF receptor mRNAs. Computerized image analysis revealed that approximately 15% of GHRH-hybridizing neurons in the Arc expressed the sst1 receptor gene, whereas 15% coexpressed sst2 mRNA. These studies are the first to colocalize any SRIF receptor subtype in GHRH mRNA-containing neurons in brain. The results suggest that, in the Arc, SRIF may directly modulate GHRH release into the hypophyseal portal blood, and thereby influence GH secretion, through interaction with both sst1 and sst2 receptor subtypes.

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