JP: PACAP, an autocrine/paracrine regulator of gonadotrophs

Hypothalamic-hypophysiotropic peptides are the proximate regulators of pituitary cells, but they cannot account fully for their complex functioning. Accordingly, there is growing awareness that an array of peptides produced in the pituitary exert paracrine/autocrine functions. One of these peptides is pituitary adenylate cyclase-activating polypeptide (PACAP) that was originally identified as a hypothalamic activator of cAMP production in pituitary cells. Gonadotrophs and folliculostellate cells are the main source of pituitary PACAP while each of the pituitary cell types expresses a PACAP receptor. PACAP increases alpha-subunit (Cga) and Lhb mRNAs, and stimulates the transcription of follistatin (Fst) that, in turn, restrains activin signaling to repress Fshb and GnRH-receptor (Gnrhr) expression as well as other activin-responsive genes. The PACAP (Adcyap1) promoter is activated by cAMP, and pituitary cells may communicate by a feed-forward cAMP dependent mechanism to maintain a high level of PACAP in the fetal pituitary. At birth, pituitary PACAP declines and pituitary follistatin levels decrease, which together with increased GnRH secretion, allow Gnrhr and Fsh