Hazlerigg D G, Hastings M H, Morgan P J
Department of Anatomy, University of Cambridge, UK.
J Endocrinol. 1994 Jul;142(1):127-38. doi: 10.1677/joe.0.1420127.
The pars tuberalis (PT) of the anterior pituitary is characterized by the presence of a high concentration of melatonin receptors, and acute exposure of cells from this tissue to melatonin inhibits the accumulation of cyclic AMP (cAMP) stimulated by forskolin. Conversely, exposure of ovine PT (oPT) cells to melatonin for periods of up to 16 h causes a progressive increase in subsequent basal and forskolin-stimulated production of cAMP. These observations are consistent with the possibility that the PT is involved in the mediation of melatonin-dependent phenomena in mammals. If the chronic effects of exposure to melatonin are indeed functionally significant, then one would anticipate that those responses of oPT cells known to be dependent upon levels of cAMP would also show an enhanced response to stimulation following prolonged exposure to the hormone. In the present study, the activation of cAMP-dependent protein kinase and the synthesis of secretory protein by oPT cells were found to be sensitized by prolonged exposure to physiological concentrations of melatonin. In the case of the synthesis of secretory protein this effect of melatonin was confined to those proteins whose synthesis has been shown to be sensitive to melatonin in acute experiments. These observations support the hypothesis that melatonin-induced sensitization modulates the putative biosynthetic and secretory function of the PT. The present study also examined the mechanism of sensitization of oPT cells by melatonin. The development of sensitization was not affected by simultaneous exposure of oPT cells to forskolin (1 microM) during pretreatment with melatonin. This observation suggests that melatonin-induced sensitization occurs independently of the established acute effects of the hormone on cAMP levels in oPT cells. Since no effects of melatonin upon any other signalling cascade have been observed in these cells, the most plausible explanation for this finding is that sensitization is a direct consequence of prolonged activation of melatonin receptors. Such a mechanism might be linked to the partial down-regulation of melatonin receptors known to occur in oPT cells in response to prolonged exposure to the hormone. In order to test this hypothesis further, the process of recovery from the sensitizing effects of melatonin was examined. The recovery of oPT cells from the sensitizing effects of exposure to melatonin (100 pM, 16 h) took place gradually and, even after an interval of 16 h, cells that had previously been exposed to melatonin for 16 h remained sensitized to approximately 20% of the extent seen immediately following pretreatment with melatonin for 16 h.(ABSTRACT TRUNCATED AT 400 WORDS)
腺垂体结节部（PT）的特点是存在高浓度的褪黑素受体，该组织的细胞急性暴露于褪黑素会抑制福司可林刺激的环磷酸腺苷（cAMP）积累。相反，将绵羊PT（oPT）细胞暴露于褪黑素长达16小时，会使随后基础状态下以及福司可林刺激的cAMP产生逐渐增加。这些观察结果与PT参与哺乳动物中褪黑素依赖性现象的介导这一可能性相一致。如果暴露于褪黑素的慢性影响在功能上确实具有重要意义，那么可以预期，那些已知依赖于cAMP水平的oPT细胞反应，在长时间暴露于该激素后对刺激的反应也会增强。在本研究中，发现长时间暴露于生理浓度的褪黑素会使oPT细胞中cAMP依赖性蛋白激酶的激活以及分泌蛋白的合成变得敏感。就分泌蛋白的合成而言，褪黑素的这种作用仅限于那些在急性实验中已显示其合成对褪黑素敏感的蛋白质。这些观察结果支持了褪黑素诱导的敏感性调节PT假定的生物合成和分泌功能这一假说。本研究还探讨了褪黑素使oPT细胞敏感化的机制。在褪黑素预处理期间，oPT细胞同时暴露于福司可林（1微摩尔），这并不影响敏感性的发展。这一观察结果表明，褪黑素诱导的敏感性独立于该激素对oPT细胞中cAMP水平已确定的急性影响而发生。由于在这些细胞中未观察到褪黑素对任何其他信号级联反应的影响，对此发现最合理的解释是，敏感性是褪黑素受体长时间激活的直接结果。这样一种机制可能与已知在oPT细胞中因长时间暴露于该激素而发生的褪黑素受体部分下调有关。为了进一步验证这一假说，研究了从褪黑素的致敏作用中恢复的过程。oPT细胞从暴露于褪黑素（100皮摩尔，16小时）的致敏作用中恢复是逐渐发生的，并且即使在间隔16小时后，先前暴露于褪黑素16小时的细胞对刺激的敏感性仍保持在预处理16小时后立即观察到的约20%的水平。（摘要截断于400字）
