Co-expression of the calcitonin receptor gene in the hypothalamic kisspeptin neurons in female rats.

Purpose: Hypothalamic kisspeptin neurons are considered to play a critical role in regulating mammalian reproduction and integrating humoral and neuronal inputs that control gonadotropin-releasing hormone (GnRH)/gonadotropin release. The present study aimed to investigate the upstream regulator candidates for kisspeptin neurons.

Methods: Visualized kisspeptin neurons that were taken from the arcuate nucleus (ARC) of Kiss1 -tdTomato rats were subjected to next-generation sequencing (NGS) analysis. In situ hybridization (ISH) for the calcitonin receptor gene ( Calcr ) was performed throughout the whole forebrain of ovariectomized wild-type female rats that had been implanted with a negative feedback level of estrogen, because the Calcr expression was evident in the ARC kisspeptin neurons from the NGS analysis. Then, a double ISH was performed for the Calcr and kisspeptin gene ( Kiss1 ) in the brain regions, containing either the anteroventral periventricular nucleus (AVPV) or ARC of the female rats.

Results: The NGS analysis revealed that the Calcr was highly expressed in the ARC kisspeptin neurons. It was found that the Calcr was co-expressed in 12% and 22% of the Kiss1 -expressing cells in the ARC and AVPV, respectively.

Conclusion: The present study suggests that calcitonin receptor signaling could be involved in the regulation of reproductive function through the direct control of the ARC and/or AVPV kisspeptin neurons, and then GnRH/gonadotropin release.