Department of Physiology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo 409-3898, Japan.
Endocr J. 2013;60(11):1251-9. doi: 10.1507/endocrj.ej13-0245. Epub 2013 Aug 29.
There are differences in the susceptibility of rat strains to pituitary growth and lactotroph proliferation caused by long-term treatment with estrogens. To investigate the pituitary mechanism for this strain difference in estrogen-induced lactotroph proliferation, we compared the abilities of 17-β estradiol (E2) and insulin-like growth factor-1 (IGF-1) to modulate lactotroph proliferation and gene expression in vitro in Wistar and Wistar-Kyoto (WKY) rats. These two strains of rats have a high and very low susceptibility to estrogen, respectively. Long-term in vivo treatment with E2 was confirmed to markedly increase pituitary weight and lactotroph proliferation in ovariectomized Wistar, but not in WKY rats. Pituitary lactotrophs in primary cultures showed similar proliferative responsiveness to the culture condition-dependent, stimulatory and inhibitory actions of E2 in both strains. The only difference in lactotroph proliferation in vitro was a lower response to IGF-1 in WKY cells compared with Wistar cells. This difference in proliferation was associated with strain differences in IGF-1-induced gene expression in Wistar and WKY cultured cells. Of the genes tested, IGF-1-induced expression of the Wnt4, Stc1, Mybl1, and Myc genes was attenuated or abolished in WKY cells. These results suggest that the proliferative response to estrogen in lactotrophs in primary culture does not reflect the proliferative response to long-term estrogen treatment observed in vivo in Wistar and WKY rats. The strain difference in proliferation and gene expression to IGF-1 may be implicated in the variable degree of susceptibility for lactotroph proliferation observed in different strains of rats following long-term estrogen treatment.
长期用雌激素处理会导致大鼠品系对垂体生长和催乳素细胞增生的敏感性存在差异。为了研究这种雌激素诱导催乳素细胞增生的品系差异的垂体机制，我们比较了 17-β 雌二醇（E2）和胰岛素样生长因子-1（IGF-1）在体外调节 Wistar 和 Wistar-Kyoto（WKY）大鼠催乳素细胞增生和基因表达的能力。这两种大鼠品系对雌激素的敏感性分别很高和很低。长期体内用 E2 处理被证实能显著增加去卵巢 Wistar 大鼠的垂体重量和催乳素细胞增生，但不能增加 WKY 大鼠的垂体重量和催乳素细胞增生。原代培养的垂体催乳素细胞对 E2 的培养条件依赖性、刺激和抑制作用的增殖反应在两种品系中相似。体外催乳素细胞增殖的唯一差异是 WKY 细胞对 IGF-1 的反应低于 Wistar 细胞。这种增殖差异与 Wistar 和 WKY 培养细胞中 IGF-1 诱导的基因表达的品系差异有关。在所测试的基因中，WKY 细胞中 IGF-1 诱导的 Wnt4、Stc1、Mybl1 和 Myc 基因的表达减弱或被消除。这些结果表明，原代培养的催乳素细胞对雌激素的增殖反应并不反映在 Wistar 和 WKY 大鼠体内长期雌激素处理观察到的增殖反应。IGF-1 增殖和基因表达的品系差异可能与不同大鼠品系在长期雌激素处理后催乳素细胞增生的易感性不同有关。
