Antagonism of type II, but not type I glucocorticoid receptors results in elevated basal luteinizing hormone release in male rats.
Antagonism of type II, but not type I glucocorticoid receptors results in elevated basal luteinizing hormone release in male rats.
复制标题
II 型糖皮质激素受体（而非 I 型糖皮质激素受体）的拮抗作用会导致雄性大鼠基础黄体生成素释放升高。
DOI：
10.1159/000126803
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发表时间：
1994
影响因子：
4.1
通讯作者：
Sylvester,PW
中科院分区：
文献类型：
--
作者：
Briski,KP;Sylvester,PW
本研究利用药理学方法评估了皮质激素偏好矿皮质激素受体（I型或MR）与经典糖皮质激素受体（II型或GR）在雄性大鼠体内调节垂体基底黄体生成素（LH）分泌中的作用。植入心内静脉留置导管的动物皮下注射MR拮抗剂RU 752（0.5或5.0 mg/kg体重）或GR拮抗剂RU 486（0.5或5.0 mg/kg体重）。另外两组大鼠分别植入留置脑室插管和静脉留置导管进行给药和取血，并在脑室内注射载体剂量或分级剂量（0.1、1.0或10.0µg/大鼠）的RU 752或RU 486。mrru 752无论剂量或给药途径如何，都不能改变血浆LH浓度。相比之下，GR拮抗剂RU 486在给予s.c.c.或c.c.v时，引起了循环LH的显著剂量依赖性增加。注射s.c.c.的动物每公斤体重0.5或5.0 mg RU 486均显示血浆LH水平升高；虽然这种分泌反应的强度在两个药物治疗组之间没有差异，但在给予较高剂量的大鼠中，激素水平在较长时间内保持高于基线水平。以1.0或10.0µg的剂量给药RU 486也导致LH释放升高；血浆LH升高的幅度和持续时间都是剂量依赖性的。在另外的实验中，各组大鼠在给药RU 486之前分别用对照物或合成GR激动剂RU 362进行预处理。这些研究表明，RU 486对外周LH的刺激作用被GR与外源配体的预先相互作用所消除。综上所述，GR拮抗剂RU 486能够促进完整雄性大鼠血浆LH浓度的增加，这表明内源性糖皮质激素对这些动物体内LH释放具有强直性抑制作用，而GR介导了这种抑制作用。观察结果表明，通过GR激动剂RU 362预处理，药物诱导的循环LH升高被消除，这表明RU 486对激素释放的刺激作用是通过抗糖皮质激素作用实现的。目前的研究发现，颅内给药RU 486后血浆LH增加，暗示中枢GR在调节垂体LH的神经内分泌机制中起作用。
The present studies utilized a phaimacologic approach to evaluate the role of corticosterone-preferring mineralocorticoid receptors (type I or MR) versus classic glucocorticoid receptors (type II or GR) in the regulation of basal pituitary luteinizing hormone (LH) secretion in vivo in male rats. Animals bearing indwelling intracardiac venous catheters received a subcutaneous (s.c.) injection of either vehicle, the MR antagonist, RU 752 (0.5 or 5.0 mg/kg body weight), or the GR antagonist, RU 486 (0.5 or 5.0 mg/kg body weight). Additional groups of rats were implanted with indwelling intracerebroventricular (i.c.v.) cannulas and intravenous catheters for drug administration and blood withdrawal, respectively, and injected i.c.v. with vehicle or graded doses (0.1, 1.0 or 10.0 µg/rat) of RU 752 or RU 486. The MR RU 752 failed to alter plasma LH concentrations regardless of dose or route of administration. In contrast, the GR antagonist, RU 486, elicited significant, dose-dependent increases in circulating LH when given either s.c. or i.c.v. Animals injected s.c. with either 0.5 or 5.0 mg RU 486/kg body weight showed elevated plasma LH levels; while the magnitude of this secretory response was not different between the two drug-treated groups, hormone levels remained elevated over baseline for a longer period of time in rats given the higher dose. Central administration of RU 486 at a dose of either 1.0 or 10.0 µg also resulted in elevated LH release; both the magnitude and duration of this increase in plasma LH were dose-dependent. In additional experiments, groups of rats were pretreated with vehicle or the synthetic GR agonist, RU 362, before administration of RU 486. These studies showed that the stimulatory effect of RU 486 on peripheral LH was abolished by prior interaction of GR with the exogenous ligand. In summary, the ability of the GR antagonist, RU 486, to promote an increase in plasma LH concentrations in intact male rats suggests that endogenous glucocorticoids exert a tonic inhibitory tonus on in vivo LH release in these animals, and that GR mediate these suppressive effects. Observations that drug-induced elevations in circulating LH were abolished by pretreatment with the GR agonist, RU 362, suggest that the stimulatory effects of RU 486 on hormone release were achieved by an antiglucocorticoid action. The current findings that plasma LH was increased following intracranial administration of RU 486 implicate central GR in neuroendocrine mechanisms governing pituitary LH.