Anti-CALCR monoclonal antibody, clone 31/01-1H10-4-1-14

To understand hindbrain pathways involved in the control of food intake, we examined roles for calcitonin receptor (CALCR)-containing neurons in the NTS. Ablation of NTS Calcr abrogated the long-term suppression of food intake, but not aversive responses, by CALCR agonists. Similarly, activating Calcr(NTS) Ts neurons decreased food intake and body weight but (unlike neighboring Cck(NTS) cells) failed to promote aversion, revealing that Calcr(NTS) Ts neurons mediate a non-aversive suppression of food intake. While both Calcr(NTS) and Cck(NTS) neurons decreased feeding via projections to the PBN, Cck(NTS) cells activated aversive CGRP PM cells while Calcr(NTS) Ts cells activated distinct non-CGRP PBN cells. Hence, Calcr(NTS) Ts cells suppress feeding via non-aversive, non-CGRP PBN targets. Additionally, silencing Calcr(NTS) Ts cells blunted food intake suppression by gut peptides and nutrients, increasing food intake and promoting obesity. Hence, Calcr(NTS) Ts neurons define a hindbrain system that participates in physiological energy balance and suppresses food intake without activating aversive systems.

Pulsatile gonadotropin-releasing hormone (GnRH) secretion is essential for regulating reproductive functions in mammals. GnRH pulses are governed by a neural mechanism that is termed the GnRH pulse generator. In the present study, we investigated the role of central calcitonin receptor (CTR) signaling in the regulation of the GnRH pulse generator activity in ovariectomized goats by administering amylin, an endogenous ligand for CTR, into the lateral ventricle. GnRH pulse generator activity was measured using multiple unit activity (MUA) recordings in the mediobasal hypothalamus. We analyzed changes in the interval of characteristic increases in MUA (MUA volleys). The MUA volley interval shortened immediately after amylin administration, followed by prolonged intervals. Double in situ hybridization for KISS1 (kisspeptin gene) and CALCR (CTR gene) revealed that low expression levels of CALCR were found in the arcuate kisspeptin neurons, which is suggested as the main population of neurons, involved in GnRH pulse generator activity. These results suggest that central amylin-CTR signaling has a biphasic role in the regulation of GnRH pulse generator activity by acting on cells other than the arcuate kisspeptin neurons in goats.