Involvement of Distinct Signaling Pathways in Activin-Induced Increases in FSH Secretion and Enlargement of FSH Cell Population in the Rat Pituitary

Abstract

Activin-A induces increases in FSH secretion, as well as the number of immunoreactive FSH cells, in cultured rat pituitary cells. In this study, we examined whether mechanisms involved in these two actions of activin-A are identical or not, with respect to the involvement of cellular proliferation and of Ca²⁺-dependent signaling pathways. Treatment with activin-A (25ng/ml) for 48h caused increases in the number of cultured rat anterior pituitary cells that incorporated BrdU, a thymidine analog. The stimulatory effects of activin-A on FSH secretion and on the percentage of immunoreactive FSH cells were, however, not inhibited by the presence of the mitotic inhibitor cytosine arabinoside. On the other hand, the stimulatory effect of activin-A on the percentage of immunoreactive FSH cells was completely blocked in the presence of the Ca²⁺/calmodulin kinase inhibitor KN-62 or the L-type Ca²⁺ channel blocker nicardipine. Neither of these inhibitors, however, revealed significant influence on the effect of activin-A on FSH secretion. These results suggest that activin-A exhibits its dual effect on FSH cells without causing cellular proliferation. Furthermore, activin-A appears to induce increases in FSH secretion and enlargement of FSH cell population through distinct intracellular signaling pathways, the former through Ca²⁺-independent and the latter through Ca²⁺-dependent mechanisms.