Somatostatin-somatostatin receptor 2 signaling mediates LH pulse suppression in lactating rats.

Follicular development and ovulation are profoundly suppressed during lactation in mammals. This suppression is suggested to be mainly due to the suckling-induced inhibition of kisspeptin gene (Kiss1) expression in the arcuate nucleus (ARC), and consequent inhibition of pulsatile gonadotropin releasing hormone (GnRH)/luteinizing hormone (LH) release. The present study aims to examine whether central somatostatin (SST) signaling mediates the suckling-induced suppression of pulsatile LH secretion. SST has been reported to be expressed in the posterior intralaminar thalamic nucleus (PIL), where the suckling stimulus is postulated to be relayed to the hypothalamus during lactation. SST inhibitory receptors (SSTRs) are abundantly expressed in the ARC, where kisspeptin/neurokinin B/dynorphin A (KNDy) neurons are located. Histological and quantitative studies revealed that the suckling stimulus increased the number of SST-expressing cells in the PIL, and SST receptor 2 (SSTR2) gene (Sstr2) expression in the ARC. Furthermore, a central injection of an SSTR2 antagonist caused a significant increase in pulsatile LH release in lactating rats. Double labeling of Sstr2 and the neurokinin B gene, as a marker for ARC KNDy neurons, showed that Sstr2 expression was abundantly detected in the ARC, but few KNDy neurons co-expressed Sstr2 in lactating rats. Taken together, this study suggests that the suckling-induced activation of SST-SSTR2 signaling mediates, at least in part, the suppression of pulsatile LH secretion during lactation in rats, probably via the indirect effects of SST on KNDy neurons. These results provide a new aspect of the role of central SST-SSTR signaling in understanding the mechanism underlying lactational anestrus.