Hyde J F, Howard G
Department of Anatomy and Neurobiology, University of Kentucky Medical Center, Lexington 40536.
Endocrinology. 1992 Nov;131(5):2097-102. doi: 10.1210/endo.131.5.1385097.
In addition to inducing pituitary tumors in rats, estrogen (E2) markedly increases galanin and PRL gene expression. We previously showed that galanin secretion from pituitary cells in vitro is inhibited by dopamine and somatostatin and stimulated by TRH. The objectives of these in vivo studies were to assess whether the long-acting somatostatin analog SMS 201-995 alters 1) immunoreactive galanin or PRL levels in the anterior pituitary, neurointermediate lobe, hypothalamus, or plasma, 2) pituitary galanin and PRL mRNA levels, and 3) the development of E2-induced pituitary tumors. Ovariectomized Fischer 344 rats were implanted with E2-filled or empty Silastic capsules and treated with or without SMS 201-995 (1.5 mg) via Alzet miniosmotic pumps. Two or 6 weeks later, immunoreactive galanin and PRL levels were determined by RIA. In ovariectomized rats, the somatostatin analog lowered the anterior pituitary content of galanin by 50%, but had no effect on PRL concentrations. E2 increased galanin and PRL levels in the anterior pituitary by 220- and 4-fold, respectively. Concomitant E2 and SMS 201-995 treatment further increased galanin and PRL in the anterior pituitary by 60-80%, but decreased plasma galanin and PRL levels. Likewise, the administration of SMS 201-995 for 2 and 6 weeks inhibited the E2-induced growth of the anterior pituitary. Galanin and PRL mRNA levels were quantified by solution hybridization. Galanin mRNA levels were reduced to undetectable levels in ovariectomized rats treated with SMS 201-995. Furthermore, a 10-fold increase in galanin mRNA levels seen in the presence of E2 was inhibited 80% by SMS 201-995. PRL mRNA levels in E2-treated rats were unchanged by SMS 201-995. We conclude that SMS 201-995 1) lowers plasma galanin and PRL levels in E2-treated rats, 2) elevates the anterior pituitary contents of galanin and PRL in E2-exposed rats, probably through decreased secretion of the hormones, and 3) reduces galanin mRNA levels in E2-treated and untreated ovariectomized rats. Overall, these results establish the differential regulation of galanin and PRL gene expression in vivo by SMS 201-995. Moreover, the data demonstrate that somatostatin receptor agonists may have therapeutic potential for some prolactinomas.
除了在大鼠中诱发垂体肿瘤外，雌激素（E2）还显著增加甘丙肽和催乳素（PRL）的基因表达。我们之前发现，体外培养的垂体细胞分泌甘丙肽受到多巴胺和生长抑素的抑制，而受到促甲状腺激素释放激素（TRH）的刺激。这些体内研究的目的是评估长效生长抑素类似物SMS 201-995是否会改变：1）垂体前叶、神经中间叶、下丘脑或血浆中免疫反应性甘丙肽或PRL水平；2）垂体甘丙肽和PRL mRNA水平；3）E2诱导的垂体肿瘤的发生。对切除卵巢的Fischer 344大鼠植入填充E2或空的硅橡胶胶囊，并通过Alzet微型渗透泵给予或不给予SMS 201-995（1.5毫克）。2周或6周后，通过放射免疫分析（RIA）测定免疫反应性甘丙肽和PRL水平。在切除卵巢的大鼠中，生长抑素类似物使垂体前叶甘丙肽含量降低了50%，但对PRL浓度没有影响。E2使垂体前叶甘丙肽和PRL水平分别增加了220倍和4倍。E2与SMS 201-995联合治疗使垂体前叶甘丙肽和PRL进一步增加了60%-80%，但降低了血浆甘丙肽和PRL水平。同样，给予SMS 201-995 2周和6周可抑制E2诱导的垂体前叶生长。通过溶液杂交对甘丙肽和PRL mRNA水平进行定量。在接受SMS 201-995治疗的切除卵巢的大鼠中，甘丙肽mRNA水平降至无法检测的水平。此外，在有E2存在时观察到的甘丙肽mRNA水平增加10倍的情况被SMS 201-995抑制了80%。SMS 201-995对E2处理的大鼠中的PRL mRNA水平没有影响。我们得出结论：1）SMS 201-995降低E2处理大鼠的血浆甘丙肽和PRL水平；2）可能通过减少激素分泌，提高E2暴露大鼠垂体前叶中甘丙肽和PRL的含量；3）降低E2处理和未处理的切除卵巢大鼠中的甘丙肽mRNA水平。总体而言，这些结果确立了SMS 201-995在体内对甘丙肽和PRL基因表达的差异调节。此外，数据表明生长抑素受体激动剂可能对某些催乳素瘤具有治疗潜力。
