Role of pituitary adenylate cyclase‐activating polypeptide in modulating hypothalamic‐pituitary system

Background

Pituitary adenylate cyclase‐activating polypeptide (PACAP) is a multifunctional peptide that is isolated and identified from the ovine hypothalamus, whose effects and mechanisms have been elucidated in numerous studies. The PACAP and its receptor are widely expressed, not only in the hypothalamus but also in peripheral organs.

Methods

The studies on the role of PACAP in the hypothalamic‐pituitary system, including those by the authors, were summarized.

Results

In the pituitary gonadotrophs, PACAP increases the gonadotrophin α‐, luteinizing hormoneβ‐, and follicle‐stimulating hormone β‐subunit expression and the expression of gonadotropin‐releasing hormone (GnRH) receptor and its own receptor, PAC1R. Moreover, a low‐frequency GnRH pulse increases the expression of PACAP and PAC1R more than a high‐frequency GnRH pulse in the gonadotrophs. The PACAP stimulates prolactin synthesis and secretion and increases PAC1R in the lactotrophs. In the hypothalamus, PACAP increases the expression of the GnRH receptors, although it is unable to increase the expression of GnRH in the GnRH‐producing neurons.

Conclusion

The PACAP not only acts directly in each hormone‐producing cell, it possibly might regulate hormone synthesis via the expression of its own receptors or those of other hormones.     

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.