PACAP in the reproductive system

The production of a mature oocyte that is capable of being fertilized and undergoing embryo development is the major function of the female reproductive system. This process depends on the close association between germ cells and somatic cells, i.e., granulosa and theca cells. The growth of the mammalian oocyte is finely regulated by the coordinate expression of autocrine and paracrine factors. The initial phases of folliculogenesis are independent from gonadotropins, but at later stages, it is strictly dependent on follicle-stimulating hormone (FSH) and luteinizing hormone (LH). However, increasing amounts of paracrine/autocrine growth factors participate in the modulation of gonadotropin effects. Pituitary Adenylate Cyclase-Activating Peptide (PACAP) is an extremely conserved regulatory peptide that was initially found in the central nervous system. However, PACAP has been found together with its receptors in many organs, tissues and cell types, including lung, testis, adrenal gland and ovary. In the ovary, PACAP expression has been found mainly in preovulatory follicles after the LH surge. However, PACAP is constantly expressed through the ovarian cycle in the nerve fibres in the hilus region and in the interstitial tissue in the proximity of the primary follicles. In the ovary, PACAP promotes steroidogenesis and cAMP production, reduces the rate of apoptosis in granulosa cells, and accelerates oocyte meiotic maturation.