PACAP: A regulator of mammalian reproductive function

Pituitary adenylate cyclase-activating polypeptide (PACAP) is an ancestral molecule that was isolated from sheep hypothalamic extracts based on its action to stimulate cAMP production by pituitary cell cultures. PACAP is one of a number of ligands that coordinate with GnRH to control reproduction. While initially viewed as a hypothalamic releasing factor, PACAP and its receptors are widely distributed, and there is growing evidence that PACAP functions as a paracrine/autocrine regulator in the CNS, pituitary, gonads and placenta, among other tissues. This review will summarize current knowledge concerning the expression and function of PACAP in the hypothalamic-pituitary-gonadal axis with special emphasis on its role in pituitary function in the fetus and newborn. •PACAP and its receptors are co-expressed in the pituitary and gonads, implying a paracrine role in reproductive functioning.•PACAP stimulates expression of each of the gonadotropin subunits while stimulation of follistatin blocks activin signalling.•PACAP stimulates its own promoter through cAMP to establish a feed forward mechanism for rapid changes in expression.•Pituitary PACAP and follistatin decline dramatically at birth allowing GnRH-R and FSH-b to increase and initiate sexual maturation.