PACAP was isolated in 1989 from extracts of hypothalamus on the basis of its capacity for stimulating adenylate cyclase in pituitary gland cells in culture. 1 Since its discovery, the role of PACAP in the regulation of anterior pituitary functions has been much studied. 2, 3 The type I receptor, PAC1, is the major PACAP receptor expressed in the pituitary gland. 3–5 In particular, it was reported that PACAP, via a type I receptor, stimulated LH and FSH release from anterior pituitary cells, and synergistically with GnRH. 1, 6, 7 In vivo, the effect on gonadotropin release was less clear, with differences among species. 3 For LH/FSH synthesis, a continuous treatment of PACAP decreased the FSH-β mRNA level, but pulsatile treatment stimulated LH-β mRNA. 7, 8 In addition, it was suggested that PAC1, expressed in ovary and testis, plays a role in ovocyte maturation and in Sertoli cells function. 9–13 We have generated PAC1 KO mice and used them to look at the anterior pituitary function related to fertility and the reproduction process.