Colocalization of somatostatin receptor subtypes (SSTR1-5) with somatostatin, NADPH-diaphorase (NADPH-d), and tyrosine hydroxylase in the rat hypothalamus.

The hypothalamus is a major site of somatostatin (SST) production and action. SST is synthesized in several hypothalamic nuclei and involved in a variety of functions. Using SST receptor (SSTR)-specific antibodies, we localized SSTR subtypes in the rat hypothalamus. In addition, we also demonstrated SSTRs colocalization with SST, NADPH-diaphorase (NADPH-d), and tyrosine hydroxylase (TH). SSTR1 is strongly localized in neurons in all major hypothalamic nuclei as well as in nerve fibers in the zona externa of the median eminence and the ependyma of the third ventricle. SSTR2 is also well expressed in most regions but with a relatively lower abundance in comparison to SSTR1. In contrast, SSTR3 is localized primarily in the paraventricular nucleus, dorsomedial hypothalamic nucleus, arcuate nucleus, and median eminence. SSTR4-like immunoreactivity is mainly confined to the arcuate nucleus, ventromedial hypothalamic nucleus, median eminence, and ependymal cells of third ventricle, with the rare SSTR4-positive neuron in the paraventricular nucleus. SSTR5 is the least expressed subtype occurring only in few cells in the inner layer of the median eminence. Overall, SSTR1 is the predominant subtype, followed by SSTR2, 4, 3, and 5. Combined immunofluorescence, immunocytochemistry, and histochemistry were used to demonstrate SSTRs colocalization with SST, TH, and NADPH-d. SSTRs colocalization with SST, TH, and NADPH-d displays in a region and receptor specificity. Colocalization of SST and NADPH-d with SSTRs in hypothalamic regions was similar, suggesting that SST and NADPH-d producing cells are same. In contrast, TH was selectively coexpressed with SSTRs in the hypothalamus in a receptor-specific manner. Taken together, these data suggest that SSTRs may interact with NADPH-d and TH to exert a physiological role in concert within the hypothalamus.