A role of pituitary adenylate cyclase activating polypeptide (PACAP) as a regulator of paracrine interactions between folliculo-stellate cells and gonadotropes through the control of activin-follistatin interactions

Pituitary folliculo-stellate (FS) cells were able to modify the effect of a ctivin-A on gonadotropes through the paracrine factor, follistatin. The pre sent study was aimed to examine whether a hypothalamic peptide, pituitary a denylate cyclase activating polypeptide (PACAP), could be a regulator of th is paracrine interaction. Go-culture of FS cell-originated cell line TtT/GF cells with rat anterior pituitary cells showed faint inhibitory effect on the stimulatory action of activin-ii on FSH secretion. When PACAP was added to the culture during the co-culture period, however, the presence of TtT/ GF cells caused significant suppression of the effect of activin-A on FSH s ecretion. Conditioned-media (CM) from TtT/GF cells, obtained by incubation of TtT/GF cells in the presence or absence of PACAP, were next added to the cultures of anterior pituitary cells alone. CM from TtT/GF cells without P ACAP treatment revealed slight, but not significant, suppressive effect on activin-induced increases in FSH secretion and the percentage of FSH cells. Meanwhile, CM from PACAP-treated TtT/GF cells attenuated both effects of a ctivin-A. Furthermore, the inhibitory effect of the CM was neutralized when follistatin antibody was present in the culture. These results suggest tha t PACAP is able to regulate the paracrine action of FS cells on pituitary g onadotropes. Besides expressing direct actions on pituitary endocrine cells , PACAP may have roles as a regulator of cell-to-cell interactions within t he pituitary gland.