Specific, estrogen-sensitive alterations in anterior pituitary cytoplasmic and nuclear estrogen receptors actuated by LHRH.
Specific, estrogen-sensitive alterations in anterior pituitary cytoplasmic and nuclear estrogen receptors actuated by LHRH.
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由 LHRH 驱动的垂体前叶细胞质和核雌激素受体的特异性雌激素敏感变化。
DOI：
10.1159/000123526
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发表时间：
1983
影响因子：
4.1
通讯作者：
Muldoon,TG
中科院分区：
文献类型：
--
作者：
Singh,P;Muldoon,TG
我们之前已经证明，LHRH能够引起垂体前叶核雌激素受体（E2R）水平的显著和直接升高[18,24]。这种作用在体外和体内条件下都表现出来，不能归因于细胞质E2R结合、激活或易位的速率或程度的扩增。鉴于这些观察结果在雌激素-LHRH相互作用调节促性腺激素分泌方面的意义，我们进一步探讨了LHRH作用的性质、特异性和雌激素依赖性。在体外培养后，比较了长效激动剂（D-Ala6, des-Gly10）LHRH- n -乙基酰胺（LHRH- a）和拮抗剂N-Ac-D-p-Cl-Phe12， D-Trp3, D-Phe6, D-Ala10-LHRH （LHRH- ant）与LHRH改变室室E2R浓度的能力。受体来源为完整的分散的垂体前叶细胞或分离的垂体匀浆细胞质和细胞核。37℃孵育30 min后，LHRH- a和LHRH均导致完整细胞胞质E2R结合能力下降40-60%；在0.1-1000 pmol/垂体的肽范围内，抑制的大小与剂量无关。相反，TRH引起细胞质E2R结合的剂量相关降低。当评估核E2R水平时，LHRH和LHRH- a治疗均观察到显著的剂量依赖性增加。LHRH- a的有效剂量比LHRH低约一个数量级。另一方面，在较宽的浓度范围内（0.3 ~ 3000 pmol/垂体），TRH对特异性核雌激素结合无显著影响。在分离细胞核中，与完整细胞研究一样，LHRH和LHRH- a具有刺激作用，而TRH不影响E2R结合水平的改变。LHRH- ant可完全阻断LHRH效应。在分离细胞质中，TRH不影响E2R结合，而LHRH和LHRH- a均有轻度刺激作用。LHRH增强核E2R结合的有效性与动物内源性雌激素滴度直接相关。经0.1 μg雌二醇/d诱导的去卵巢动物组织中，LHRH对核E2R的刺激作用比未诱导的去势动物组织强4倍。当剂量增加到1.0 μg/d时，核E2R对LHRH的敏感性在0.1 μg的剂量水平上进一步显著增加。这些研究结果证实了垂体前叶E2R水平变化的释放激素特异性，并证实了雌激素-LHRH致敏参与了这一过程，类似于已被充分证实的雌激素-LHRH相互作用调节LHRH的释放。
We have previously demonstrated that LHRH is capable of eliciting a dramatic and direct elevation of anterior pituitary levels of nuclear estrogen receptors (E2R) [18, 24]. This action was manifest under both in vitro and in vivo conditions, and could not be attributed to an amplification of the rate or extent of cytosol E2R binding, activation or transloca-tion. In view of the implications of these observations in terms of estrogen-LHRH interplay in regulation of gonadotropin secretion, we have further explored the nature, specificity and estrogen dependency of the LHRH effect. TRH, a long-acting agonist, (D-Ala6, des-Gly10)LHRH-N-ethylamide (LHRH-A), and an antagonist, N-Ac-D-p-Cl-Phe12, D-Trp3, D-Phe6, D-Ala10-LHRH (LHRH-ANT), were compared with LHRH for their ability to alter compartmental E2R concentrations following incubation in vitro. Either intact dispersed anterior pituitary cells or isolated cytosol and nuclei from pituitary homogenates were used as receptor source. LHRH-A and LHRH both caused a 40–60% decrease in the cytoplasmic E2R binding capacity of intact cells following incubation of 30 min at 37 °C; the magnitude of the inhibition was dose independent over a peptide range of 0.1–1000 pmol/pituitary. In contrast, TRH caused a dose-related decrease in cytosol E2R binding. When nuclear E2R levels were assessed, significant dose dependent increases were observed with both LHRH and LHRH-A treatment. The effective dose of LHRH-A was approximately an order of magnitude lower than that of LHRH. TRH, on the other hand, over a wide concentration range (0.3–3,000 pmol/pituitary), had no significant effect on specific nuclear estrogen binding. In isolated nuclei, as in the intact cell studies, LHRH and LHRH-A were stimulatory, while TRH effected no alteration of E2R binding levels. The LHRH effect could be totally blocked by LHRH-ANT. In isolated cytosol, TRH did not affect E2R binding, whereas LHRH and LHRH-A were both mildly stimulatory. The effectiveness of LHRH in enhancing nuclear E2R binding correlated directly with the endogenous estrogen titers of the animals. In tissue from ovariectomized animals primed with 0.1 μg estradiol/day, LHRH was 4 times more potent as a stimulator of nuclear E2R than in tissue from nonprimed castrate animals. If the priming dose was increased to 1.0 μg/day, a further significant increase in sensitivity of nuclear E2R to LHRH was observed over the 0.1 μg priming dose level. The results of these studies attest to the releasing hormone specificity of changes in anterior pituitary E2R levels, and to the involvement of estrogen-LHRH sensitization in this process, analogous to the well-documented estrogen-LHRH interplay in regulation of LHRH release.
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