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.