Mechanisms for gonadotropin-releasing hormone potentiation of growth hormone rebound following norepinephrine inhibition in goldfish pituitary cells

Abstract

Wong AO, Chuk MC, Chan HC, Lee EK. Mechanisms for gonadotropin-releasing hormone potentiation of growth hormone rebound following norepinephrine inhibition in goldfish pituitary cells. Am J Physiol Endocrinol Metab 292: E203-E214, 2007. First published August 29, 2006 doi:10.1152/ajpendo.00337.2006.-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 "postinhibition" 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 Ca 2ϩ entry through voltage-sensitive Ca 2ϩ channels (VSCC). Furthermore, GnRH-potentiated GH rebound could be alleviated by inactivation of PKC, removal of extracellular Ca 2ϩ , blockade of VSCC, and inhibition of Ca 2ϩ /calmodulin (CaM)-dependent protein kinase II (CaMKII). Inactivation of AC and PKA, however, was 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 Ca 2ϩ entry through VSCC and subsequent activation of CaMKII. Apparently, the Ca 2ϩ -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. protein kinase A; protein kinase C; voltage-sensitive Ca 2ϩ channel; Ca 2ϩ / calmodulin-dependent protein kinase IN MAMMALS, EPISODIC RELEASE of growth hormone (GH) is caused by the 180°out-of-phase secretion of GH-releasing hormone (GHRH) and somatostin (SRIF) from the hypothalamus (54). Recently, ghrelin, the endogenous ligand for GH secretagogues, is also known to be involved in the control of GH pulsatility (53). The functionality of these GH regulators, in turn, is under the modulation of neurotransmitters acting within the central nervous system (CNS). Adrenergic nerve fibers, presumably originated from the A 1 to A 7 groups in the brain stem (51), innervate the cell bodies of GHRH and SRIF neurons in the medial basal (47) and preoptic hypothalamus (32), respectively. Through activation of ␣ 2 -adrenoreceptors (14), adrenergic stimulation can elevate GH levels by inducing GHRH secretion from the arcuate nucleus (12) with simultaneous inhibition of SRIF release from the periventricular nucleus (31). In the rat, ␣ 2 -...

Anatomical features for the adequate choice of experimental animal models in biomedicine: I. Fishes

“…The anterior pituitary gland is innervated by numerous neuronal cell types, and thus pituitary hormone release is directly regulated. Thanks to regionalized distribution of cells in the goldfish pituitary, it has been demonstrated a unique reciprocal paracrine relationship between gonadotrophs and somatotrophs, mediated by luteinizing hormone 17 and growth hormone (Wong et al, 2007).…”