Martensz N D, Herbert J, Stacey P M
Neuroendocrinology. 1983;36(1):39-48. doi: 10.1159/000123434.
Cortisol levels in the serum and cerebrospinal fluid (CSF) were studied in ovariectomized, estrogen-treated monkeys during either prolonged hypercortisolemia or the more transient effects of a bolus injection of cortisol. Control (saline-treated) animals showed the expected diurnal rhythm in serum cortisol, but proportionately more cortisol was present in the CSF when serum levels were high (i.e. in the morning). Prolonged hypercortisolemia for up to 37 days was produced by either thrice daily injections of cortisol itself or single daily injections of ACTH1-24 in the morning. Both treatments produced disproportionately larger amounts of cortisol in the CSF than in the serum, and the CSF/serum cortisol ratio was increased. Furthermore, prolonged ACTH treatment caused a marked elevation in CSF cortisol in afternoon samples taken at 16.30 h compared with those at 10.00 h, in the absence of a similar change in serum cortisol levels. The relative importance of entry and clearance of cortisol in the CSF in these conditions was studied in several ways. 'Free' cortisol levels in serum (determined by equilibrium dialysis) were equal to CSF cortisol levels in control monkeys, but were less than those in the CSF of hypercortisolemic animals. Entry of cortisol into CSF after a bolus injection was rapid, but, unlike serum, CSF cortisol levels did not decline significantly over a 70-min sampling period and the delayed clearance from the CSF could account for some of the effects seen during hypercortisolemia. Neither high levels of prolactin (which is elevated together with cortisol in 'stress'), induced by giving sulpiride, nor treatment with progesterone (which is also bound by corticosteroid binding globulin) altered the distribution of cortisol between blood and CSF. The concentrations of cortisol in the CSF therefore are regulated by factors influencing both its entry and clearance from the cerebral compartment. Neural tissues sensitive to cortisol are thus exposed to levels of this hormone that are both qualitatively and quantitatively different from those expected by direct extrapolation from serum levels.
在长期高皮质醇血症期间或静脉注射皮质醇产生的更短暂效应期间，对去卵巢并用雌激素处理的猴子的血清和脑脊液（CSF）中的皮质醇水平进行了研究。对照（盐水处理）动物的血清皮质醇呈现预期的昼夜节律，但当血清水平较高时（即早晨），脑脊液中的皮质醇含量相对更高。通过每天三次注射皮质醇本身或每天早晨单次注射促肾上腺皮质激素1 - 24，可产生长达37天的长期高皮质醇血症。两种处理方式在脑脊液中产生的皮质醇量均比血清中不成比例地大，且脑脊液/血清皮质醇比值增加。此外，与上午10:00采集的样本相比，在下午16:30采集的样本中，长期促肾上腺皮质激素处理导致脑脊液皮质醇显著升高，而血清皮质醇水平无类似变化。通过几种方式研究了在这些情况下皮质醇进入和清除脑脊液的相对重要性。血清中“游离”皮质醇水平（通过平衡透析测定）在对照猴子中与脑脊液皮质醇水平相等，但低于高皮质醇血症动物脑脊液中的水平。静脉注射后皮质醇进入脑脊液的速度很快，但与血清不同，在70分钟的采样期内脑脊液皮质醇水平没有显著下降，脑脊液中清除延迟可能是高皮质醇血症期间所见一些效应的原因。给予舒必利诱导的高水平催乳素（在“应激”时与皮质醇一起升高）或孕酮处理（孕酮也与皮质类固醇结合球蛋白结合）均未改变皮质醇在血液和脑脊液之间的分布。因此，脑脊液中皮质醇的浓度受影响其进入和从脑区清除的因素调节。对皮质醇敏感的神经组织因此暴露于该激素的水平，这些水平在质量和数量上均与直接从血清水平外推预期的水平不同。
