Ratka A, Sutanto W, Bloemers M, de Kloet E R
Rudolf Magnus Institute for Pharmacology, Medical Faculty, University of Utrecht, The Netherlands.
Neuroendocrinology. 1989 Aug;50(2):117-23. doi: 10.1159/000125210.
Administrations of the glucocorticoid receptor antagonist (anti-glucocorticoid, RU38486) and the mineralocorticoid antagonist (anti-mineralocorticoid, RU28318) followed by frequent, sequential blood sampling were employed to investigate the possible role the brain mineralocorticoid receptor (MR, type I) and glucocorticoid receptor (GR, type II) have in the regulation of basal and stress-induced adrenocortical secretion in the rat. The anti-mineralocorticoid and anti-glucocorticoid were administered subcutaneously (s.c.) at doses of 2.5 mg and 1.0 mg/100 g body weight, respectively. Both antagonists were also given intracerebroventricularly (i.c.v.) at a dose of 100 ng/rat. Under basal non-stressed conditions (at the diurnal trough in the morning), injections of either saline, anti-glucocorticoid (s.c. or i.c.v.) or anti-mineralocorticoid (s.c.) did not have effect on the plasma corticosterone level. The anti-mineralocorticoid given intracerebroventricularly, however, caused an elevation of plasma corticosterone up to 60 min after the injection. Exposure of the rats to a novel environment resulted in a large increase in the plasma corticosterone level, which was slightly reduced in the rats treated with the anti-glucocorticoid. In vehicle-treated rats, the level returned to basal values at 90 min, while in the anti-glucocorticoid- and anti-mineralocorticoid-treated groups, it remained elevated for prolonged periods. The present study thus shows that (1) the anti-glucocorticoid RU38486 via the brain GR has no effect on the basal plasma corticosterone level in the morning but interferes with a glucocorticoid negative feedback following stress and (2) the anti-mineralocorticoid RU28318 via the brain MR elevates the basal plasma corticosterone level and enhances adrenocortical secretion following stress.(ABSTRACT TRUNCATED AT 250 WORDS)
采用给予糖皮质激素受体拮抗剂（抗糖皮质激素，RU38486）和盐皮质激素受体拮抗剂（抗盐皮质激素，RU28318）后频繁、连续采血的方法，研究脑盐皮质激素受体（MR，I型）和糖皮质激素受体（GR，II型）在调节大鼠基础及应激诱导的肾上腺皮质分泌中可能发挥的作用。抗盐皮质激素和抗糖皮质激素分别以2.5 mg和1.0 mg/100 g体重的剂量皮下注射。两种拮抗剂也均以100 ng/大鼠的剂量脑室内注射。在基础非应激条件下（早晨昼夜低谷时），注射生理盐水、抗糖皮质激素（皮下或脑室内）或抗盐皮质激素（皮下）对血浆皮质酮水平均无影响。然而，脑室内注射抗盐皮质激素后，注射后60分钟内血浆皮质酮升高。将大鼠暴露于新环境中导致血浆皮质酮水平大幅升高，在接受抗糖皮质激素治疗的大鼠中略有降低。在给予赋形剂的大鼠中，该水平在90分钟时恢复至基础值，而在接受抗糖皮质激素和抗盐皮质激素治疗的组中，其水平长时间保持升高。因此，本研究表明：（1）抗糖皮质激素RU38486通过脑GR对早晨基础血浆皮质酮水平无影响，但会干扰应激后的糖皮质激素负反馈；（2）抗盐皮质激素RU28318通过脑MR升高基础血浆皮质酮水平并增强应激后的肾上腺皮质分泌。（摘要截短于250字）
