Effects of peripheral versus central administration of the endogenous glucocorticoid, corticosterone, and the glucocorticoid receptor agonist, RU 28362, on LH release in male rats.
Effects of peripheral versus central administration of the endogenous glucocorticoid, corticosterone, and the glucocorticoid receptor agonist, RU 28362, on LH release in male rats.
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外周与中枢给予内源性糖皮质激素、皮质酮和糖皮质激素受体激动剂 RU 28362 对雄性大鼠 LH 释放的影响。
DOI：
10.1016/0006-8993(94)01263-h
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发表时间：
1995
期刊：
影响因子：
2.9
通讯作者：
Briski,KP
中科院分区：
文献类型：
--
作者：
Briski,KP
本研究评价了合成糖皮质激素受体（GR）激动剂RU 28362和内源性非选择性受体配体皮质酮（Cort）对雄性大鼠垂体促黄体生成素（LH）分泌的影响。将类固醇皮下（s.c.）在先前植入心内静脉导管或脑室内（i. c. v.）其他动物群体。在s.c.或i. c. v.给药RU 28362; GR拮抗剂RU 38486预处理减弱了RU 28362对循环LH的抑制作用。在其他实验中，s.c.注射Cort引起不同的、剂量依赖性的LH释放模式。虽然最低外周剂量（0.25 mg Cort/kg）促进了血浆LH的短暂升高，但较高剂量对激素释放产生了逐渐增强的抑制作用。最高s.c.剂量（2.5 mg Cort/kg）的作用被RU 38486预处理逆转，但盐皮质激素受体拮抗剂RU 26752不能逆转。静脉注射分级剂量的Cort后，血浆LH水平一过性升高。最低剂量（0.1 μg Cort/大鼠）仅促进LH释放，但较高剂量（1.0和10.0 μg/动物）引起双相LH反应，其特征为血浆LH最初升高，随后降低至低于注射前基线水平。先前给予盐皮质激素受体拮抗剂RU 26752减弱了i. c. v. Cort对LH释放的刺激作用，而RU 26752和RU 38486均逆转了血浆LH的继发性下降。总之，目前的研究提供的证据表明，GR是抑制LH释放和糖皮质激素可能会采取行动，以减少LH，部分，通过在中枢神经系统内启动的机制。非选择性配体Cort的全身给药导致对LH释放的不同的、剂量依赖性的作用;高剂量的这种类固醇的抑制作用显然是由GR介导的。Cort，i. c. v.给予糖皮质激素导致血浆LH一过性升高;预先给予RU 26752可减弱激素释放的增加，这支持Cort偏好盐皮质激素受体（CR）参与Cort的中枢易化作用。目前的研究结果表明，CR和GR介导不同的影响，循环糖皮质激素对LH的释放，和剂量依赖性LH反应的Cort全身注射可能反映特定模式的占用高亲和力CR与低亲和力GR。
The current studies evaluated the effects of the synthetic glucocorticoid receptor (GR) agonist, RU 28362, and the endogenous, non-selective receptor ligand, corticosterone (Cort), on pituitary luteinizing hormone (LH) secretion in male rats. Steroids were injected subcutaneously (s.c.) in animals previously implanted with intracardiac venous catheters, or administered intracerebroventricularly (i.c.v.) to other groups of animals. A dose-proportionate decrease in plasma LH was observed following either s.c. or i.c.v. administration of RU 28362; pretreatment with the GR antagonist, RU 38486, blunted the inhibitory impact of RU 28362 on circulating LH. In other experiments, s.c. injection of Cort elicited divergent, dose-dependent patterns of LH release. While the lowest peripheral dose (0.25 mg Cort/kg) promoted a transient elevation in plasma LH, higher doses exerted a progressively greater inhibitory effect on hormone release. The suppressive effects of the highest s.c. dose (2.5 mg Cort/kg) were reversed by pretreatment with the RU 38486, but not by the mineralocorticoid receptor antagonist, RU 26752. Plasma LH levels were transiently elevated following i.c.v. administration of graded doses of Cort. The lowest dose (0.1 μg Cort/rat) only facilatated LH release, but higher doses (1.0 and 10.0 μg/animal) elicited a biphasic LH response, which was characterized by an initial elevation, then subsequent reduction in plasma LH below preinjection baseline levels. Prior administration of the mineralocorticoid receptor antagonist, RU 26752, attenuated the stimulatory impact of i.c.v. Cort on LH release, while both RU 26752 and RU 38486 reversed the secondary decline in plasma LH. In summary, the present studies provide evidence that GR are inhibitory to LH release and that glucocorticoids may act to diminish LH, in part, through mechanisms initiated within the CNS. Systemic administration of the non-selective ligand, Cort, resulted in divergent, dose-dependent effects on LH release; the inhibitory effects of high doses of this steroid are apparently mediated by GR. In contrast to the bidirectional effects of s.c. Cort, i.c.v. delivery of the glucocorticoid resulted in a transient elevation in plasma LH; attenuation of this increase in hormone release by prior administration of RU 26752 supports the involvement of Cort-preferring mineralocorticoid receptors (CR) in central facilitory actions of Cort. The current results suggest that CR and GR mediate divergent effects of circulating glucocorticoids on LH release, and that the dose-dependent LH response to systemic injections of Cort may reflect specific patterns of occupancy of high affinity CR versus low affinity GR.