G-protein coupled receptor 101 mRNA expression in the SON and PVN of the rat hypothalamus is regulated in response to pregnancy and lactation

GPCR101 is a recently identified orphan G-protein coupled receptor, which is expressed abundantly in the mouse hypothalamus. Its function in this brain region is currently unknown. In an attempt to elucidate a role for this receptor in the hypothalamus, we used the technique of in situ hybridisation to investigate (a) the distribution of the receptor, (b) the expression level of GPCR101 mRNA in different animal models of energetic challenge, and (c) the spatial relationship of the receptor to hypothalamic neuropeptides. In situ hybridisation of GPCR101 riboprobes to mouse and rat hypothalamic brain sections revealed expression in arcuate nucleus, lateral hypothalamus, paraventricular nucleus (PVN), supraoptic nucleus (SON), and suprachiasmatic nucleus. In the hypothalamic nuclei of 24 h food deprived mice or mice bearing the ob gene mutation, there was no significant change in the mRNA level of GPCR101, suggesting that there is no acute effect of energy deficit or effect of leptin on GPCR101 mRNA expression in the hypothalamus. By contrast, both pregnancy and lactation had a significant impact on the mRNA level of GPCR101, particularly in the PVN and SON. The investigation was conducted using rats that were pregnant for 5 or 21 days, lactating for 19 days and using rats 21 days following weaning of their offspring; the mRNA levels in these animals were compared with virgin controls. In the SON, the mRNA level was increased significantly at day 21 of pregnancy and at day 19 of lactation. There was no significant difference between the mRNA level in the SON at day 5 of pregnancy or day 21 after weaning compared to virgin rats. In the PVN, the change (increase) in the mRNA level was observed only at day 19 of lactation. These results suggest a potential role for GPCR 101 expressed in SON and PVN in pregnancy and/or in lactation. The present study also reveals that GPCR101 mRNA is expressed in a sub-population (approximately 47%) of arcuate neurons expressing the anorexigenic neuropeptide, cocaine and amphetamine regulated transcript, which suggests a potential functional relationship. (This work was funded by Institut de Internationales Servier, France.)