Signal transduction mechanisms mediating rapid, nongenomic effects of cortisol on prolactin release
Signal transduction mechanisms mediating rapid, nongenomic effects of cortisol on prolactin release
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DOI：
10.1016/s0039-128x(01)00197-0
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发表时间：
2002-05-01
期刊：
影响因子：
2.7
通讯作者：
Fruchtman, S
中科院分区：
文献类型：
--
作者：
Borski, RJ;Hyde, GN;Fruchtman, S
虽然人们越来越了解基因组介导的糖皮质激素作用的机制，但对于转导快速糖皮质激素作用的细胞信号传导途径知之甚少。对养殖罗非鱼喙远端 (RPD) 的研究表明，生理浓度的皮质醇会迅速抑制 PRL 的释放。RPD 是鱼垂体的一个自然隔离区域，含有 95-99% 纯催乳素 (PRL) 细胞群，易于解剖并保存在完全确定的无血清培养基中。皮质醇对 PRL 释放的减弱作用在 10-20 分钟内发生，对蛋白质合成抑制剂放线菌酮不敏感，并可通过其膜不可渗透的类似物皮质醇-21 半琥珀酸缀合牛血清白蛋白 (BSA) 进行模仿。皮质醇和生长抑素是一种已知通过膜受体抑制 PRL 释放的肽，可快速、可逆地减少细胞内游离 Ca2+ (Ca2+)，并抑制 Ca-45(2+) 流入和 BAYK-8644 诱导的 PRL 释放。初步研究表明，皮质醇（而非生长抑素）抑制 PRL 细胞膜制剂中的磷脂酶 C (PLC) 活性。此外，皮质醇和生长抑素可降低细胞内 cAMP 和膜腺苷酸环化酶活性。这些发现表明，皮质醇对 PRL 释放的急性抑制作用是通过非基因组机制发生的，涉及与质膜的相互作用以及 Ca2+ 和 cAMP 信号转导途径的抑制。皮质醇可以通过抑制 L 型电压门控通道的流入来减少 Ca-i(2+)，并可能通过 PLC/三磷酸肌醇敏感的细胞内 Ca2+ 池释放。此外，类固醇也可能抑制腺苷酸环化酶活性，从而导致 cAMP 产生减少和随后 PRL 的释放。 (C) 2002 Elsevier Science Inc. 保留所有权利。
While the mechanisms governing genomically mediated glucocorticoid actions are becoming increasingly understood, relatively little is known with regard to the cell signaling pathways that transduce rapid glucocorticoid actions. Studies of the cultured tilapia rostral pars distalis (RPD), a naturally segregated region of the fish pituitary gland that contains a 95-99% pure population of prolactin (PRL) cells and is easily dissected and maintained in a completely defined, serum-free media, indicate that physiological concentrations of cortisol rapidly inhibit PRL release. The attenuative action of cortisol on PRL release occurs within 10-20 min, is insensitive to the protein synthesis inhibitor, cycloheximide, and mimicked by its membrane impermeable analog, cortisol-21 hemisuccinate-conjugated bovine serum albumin (BSA). Cortisol and somatostatin, a peptide known to work through membrane receptors to inhibit PRL release, rapidly and reversibly reduces intracellular free Ca2+ (Ca2+), and inhibits Ca-45(2+) influx and BAYK-8644 induced PRL release. Preliminary investigations show cortisol, but not somatostatin, suppresses phospholipase C (PLC) activity in PRL cell membrane preparations. In addition, cortisol and somatostatin reduce intracellular cAMP and membrane adenylyl cyclase activity. These findings indicate that the acute inhibitory effects of cortisol on PRL release occur through a nongenomic mechanism involving interactions with the plasma membrane and inhibition of both the Ca2+ and cAMP signal transduction pathways. Cortisol may reduce Ca-i(2+) by inhibiting influx through L-type voltage-gated channels and possibly release through a PLC/inositol triphosphate sensitive intracellular Ca2+ pool. In addition, it is also likely the steroid inhibits adenylyl cyclase activity in events leading to reduced cAMP production and the subsequent release of PRL. (C) 2002 Elsevier Science Inc. All rights reserved.