Bowman M E, Robinson P J, Smith R
Maternal Health Research Centre, John Hunter Hospital, NSW, Australia.
J Neuroendocrinol. 1997 Dec;9(12):929-36. doi: 10.1046/j.1365-2826.1997.00665.x.
Corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP) are two potent stimulators for secretion of proopiomelanocortin (POMC)-derived hormones, from corticotrophs. CRH also stimulates POMC synthesis. Atrial natriuretic peptide (ANP) has been reported to inhibit POMC peptide release and is thought to act through cGMP signalling pathways. A multicolumn cell perifusion system was used to investigate the role of cGMP signalling pathways in CRH- and AVP-stimulated POMC peptide release from primary cultures of ovine or rat anterior pituitary cells. The CRH and/or AVP stimulations were applied at 30 min intervals as 5 min pulses, and the various treatments were infused over a period of 50 min, overlapping with 2 of the stimulations. ANP (10 nM) had no effect on beta-endorphin (betaEP) release from ovine cells, stimulated by 0.5 nM CRH and 5 nM AVP together, or 5 nM CRH and 50 nM AVP separately. Rat anterior pituitary cells were stimulated with 0.05 nM CRH/0.5 nM AVP or 0.5 nM CRH/5 nM AVP and treated with 1 nM or 10 nM ANP, respectively. No inhibition of ACTH or betaEP was observed. Similarly, the nitric oxide donors molsidomine (100 microM), SIN-1 (100 microM) and NaNO2 (100 microM) did not inhibit betaEP release stimulated by 0.5 nM CRH/5 nM AVP in ovine cells. The cGMP analogues 8-bromo-cGMP (10 microM and 100 microM) and dibutyryl cGMP (100 microM) also had no effect on betaEP and ACTH release from ovine or rat anterior pituitary cells. Dexamethasone (8 microM), a synthetic glucocorticoid known to block POMC synthesis and secretion of betaEP and ACTH by a distinct mechanism, was used as a control and suppressed CRH/AVP-stimulated betaEP secretion from ovine anterior pituitary cells. These results contrast with some previous studies and demonstrate that the cGMP signalling pathway in sheep or rat anterior pituitary cells does not directly inhibit secretion of POMC-derived hormones from corticotrophs.
促肾上腺皮质激素释放激素（CRH）和精氨酸加压素（AVP）是促肾上腺皮质激素细胞分泌阿黑皮素原（POMC）衍生激素的两种强效刺激物。CRH还能刺激POMC的合成。据报道，心房利钠肽（ANP）可抑制POMC肽的释放，并被认为是通过cGMP信号通路发挥作用。采用多柱细胞灌流系统研究cGMP信号通路在CRH和AVP刺激绵羊或大鼠垂体前叶细胞原代培养物释放POMC肽中的作用。CRH和/或AVP刺激以5分钟脉冲的形式每隔30分钟施加一次，各种处理在50分钟内进行灌注，与两次刺激重叠。ANP（10 nM）对0.5 nM CRH和5 nM AVP共同刺激或5 nM CRH和50 nM AVP分别刺激的绵羊细胞中β-内啡肽（βEP）的释放没有影响。用0.05 nM CRH/0.5 nM AVP或0.5 nM CRH/5 nM AVP刺激大鼠垂体前叶细胞，并分别用1 nM或10 nM ANP处理。未观察到促肾上腺皮质激素（ACTH）或βEP的抑制作用。同样，一氧化氮供体吗多明（100 μM）、SIN-1（100 μM）和亚硝酸钠（100 μM）也未抑制0.5 nM CRH/5 nM AVP刺激的绵羊细胞中βEP的释放。cGMP类似物8-溴-cGMP（10 μM和100 μM）和二丁酰cGMP（100 μM）对绵羊或大鼠垂体前叶细胞中βEP和ACTH的释放也没有影响。地塞米松（8 μM）是一种合成糖皮质激素，已知通过一种独特的机制阻断POMC的合成以及βEP和ACTH的分泌，用作对照并抑制CRH/AVP刺激的绵羊垂体前叶细胞中βEP的分泌。这些结果与之前的一些研究形成对比，表明绵羊或大鼠垂体前叶细胞中的cGMP信号通路不会直接抑制促肾上腺皮质激素细胞分泌POMC衍生的激素
