Small GTPase control of pituitary hormone secretion: Evidence from studies in the goldfish (Carassius auratus) neuroendocrine model.

The secretion of vertebrate pituitary hormones is regulated by multiple hypothalamic factors, which, while generally activating unique receptor systems, ultimately propagate signals through interacting intracellular regulatory elements to modulate hormone exocytosis. One important family of intracellular regulators is the monomeric small GTPases, a subset of which (Arf1/6, Rac, RhoA, and Ras) is highly conserved across vertebrates and regulates secretory vesicle exocytosis in many cell types. In this study, we investigated the roles of these small GTPases in basal and agonist-dependent hormone release from dispersed goldfish (Carassius auratus) pituitary cells in perifusion experiments. Inhibition of these small GTPases elevated basal LH and GH secretion, except for Ras inhibition which only increased basal LH release. However, variable responses were observed with regard to LH and GH responses to the two goldfish native gonadotropin-releasing hormones (GnRH2 and GnRH3). GnRH-dependent LH release, but not GH secretion, was mediated by Arf1/6 GTPases. In contrast, inhibition of Rac and RhoA GTPases selectively enhanced GnRH3- and GnRH2-dependent GH release, respectively, while Ras inhibition only enhanced GnRH3-evoked LH secretion. Together, our results reveal novel divergent cell-type- and ligand-specific roles for small GTPases in the control of goldfish pituitary hormone exocytosis in unstimulated and GnRH-evoked release.