Mechanisms for gonadotropin-releasing hormone potentiation of growth hormone rebound following norepinephrine inhibition in goldfish pituitary cells.
In the goldfish, norepinephrine (NE) inhibits growth hormone (GH) secretion through activation of pituitary alpha(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, alpha(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(2+) entry through voltage-sensitive Ca(2+) channels (VSCC). Furthermore, GnRH-potentiated GH rebound could be alleviated by inactivation of PKC, removal of extracellular Ca(2+), blockade of VSCC, and inhibition of Ca(2+)/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(2+) entry through VSCC and subsequent activation of CaMKII. Apparently, the Ca(2+)-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.
Wong
Anderson O L
AO
Dept. of Zoology, Univ. of Hong Kong, Pokfulam Road, Hong Kong SAR, China. olwong@hkucc.hku.hk
Chuk
Maggie C Y
MC
Chan
Hiu Chi
HC
Lee
Eric K Y
EK
D000818:Animals; D002478:Cells, Cultured; D015536:Down-Regulation; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006054:Goldfish / Q000378:metabolism*; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology*; D013006:Growth Hormone / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D010902:Pituitary Gland / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism
D012333:RNA, Messenger; D007987:Gonadotropin-Releasing Hormone; D013006:Growth Hormone; D009638:Norepinephrine