Homologous upregulation of sst2 somatostatin receptor expression in the rat arcuate nucleus in vivo

In vitro studies using various cell systems have provided conflicting resul ts regarding homologous regulation of somatostatin (SRIH) receptors, and in formation on whether SRIH regulates the expression of its own receptors in vivo is lacking. In the present study we examined, by in situ hybridization , the effects of pretreatment with the sst2-preferring SRIH analog, octreot ide, in vivo, on mRNA levels of two SRIH receptor subtypes, sst1 and sst2, in rat brain and pituitary. I-125-[DTrp(8)]-SRIH binding was also measured in these regions. Three hours after the iv injection of 50 mug octreotide t o conscious adult male rats, there was a 46% increase (p < 0.01) in the lab eling density of sst2 mRNA-expressing cells in the hypothalamic arcuate nuc leus compared to normal saline-pretreated controls, but not in any of the o ther brain regions examined. Computer-assisted image analysis revealed that 3 h exposure to octreotide significantly (p < 0.01) augmented both the num ber and labeling density of sst2 mRNA-expressing cells in the arcuate nucle us, compared to those in saline-treated controls. By contrast, within the a nterior pituitary gland, in vivo exposure to octreotide did not affect the expression of sst2 mRNA. No changes in sst1 mRNA-expressing cells were obse rved after octreotide treatment in any of the regions measured, indicating that the observed effects were homologous, i.e. specific of the receptor su btype stimulated. Octreotide pretreatment was also without effect on the de nsity of I-125-[DTrp8]-SRIH binding in either the arcuate nucleus or pituit ary. These results demonstrate, for the first time, that SRIH preexposure i n vivo upregulates the expression of a subtype of its own receptors, sst2, within the central nervous system. They further suggest that pretreatment w ith SRIH in vivo does not cause sst2 receptor desensitization in arcuate nu cleus and pituitary. Such homologous regulatory mechanisms may play an impo rtant role in the neuroendocrine control of growth hormone (GH) secretion b y the arcuate nucleus. Copynght <(c)> 2001 S. Karger AG, Basel.