In the goldfish, norepinephrine (NE) inhibits growth hormone (GH) secretion through activation of pituitary 2 adrenergic receptors. Interestingly, a GH rebound is observed after NE withdrawal, which can be markedly enhanced by prior exposure to gonadotropin-releasing hormone (GnRH). Here we examined the mechanisms responsible for GnRH potentiation of this post-inhibition GH rebound. In goldfish pituitary cells, 2 adrenergic stimulation suppressed both basal and GnRH-induced GH mRNA expression, suggesting that a rise in GH synthesis induced by GnRH did not contribute to its potentiating effect. Using a column perifusion approach, GnRH given during NE treatment consistently enhanced the GH rebound following NE withdrawal. This potentiating effect was mimicked by activation of PKC and adenylate cyclase (AC) but not by induction of Ca²⁺ entry through voltage-sensitive Ca²⁺ channels (VSCC). Furthermore, GnRH-potentiated GH rebound could be alleviated by inactivating PKC, removal of extracellular Ca²⁺, blockade of VSCC, and inhibition of Ca²⁺/ calmodulin-dependent protein kinase II (CaMK II). Inactivation of AC and PKA, however, were not effective in this regard. These results, as a whole, suggest that GnRH potentiation of GH rebound following NE inhibition is mediated by PKC coupled to Ca²⁺ entry through VSCC and subsequent activation of CaMK II. Apparently, the Ca²⁺-dependent cascades are involved in GH secretion during the rebound phase but are not essential for the initiation of GnRH potentiation. Since GnRH has been previously shown to have no effects on cAMP synthesis in goldfish pituitary cells, the involvement of cAMP-dependent mechanisms in GnRH potentiation is rather unlikely.