Ciarmela Pasquapina, Wiater Ezra, Vale Wylie
The Clayton Foundation Laboratories for Peptide Biology, The Salk Institute, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.
Endocrinology. 2008 May;149(5):2506-16. doi: 10.1210/en.2007-0692. Epub 2008 Jan 31.
Activin is a pleiotropic growth factor with a broad pattern of tissue distribution that includes reproductive tissues. Although direct actions of activin have been described in gonadal and uterine tissues, actions in the myometrium have not been defined. In this study we have characterized the responsiveness of uterine tissue and myometrial cell lines to activin-A. Uterine tissue and two myometrial cell lines, PHM1 (pregnant human myometrial 1) and hTERT HM (telomerase reverse transcriptase-infected human myometrial) respond to activin-A as measured by phosphorylation of Smad-2. Those cell lines express a full complement of activin receptors, as well as activin beta(A) subunit and follistatin. Activin inhibited proliferation of PHM1 and human telomerase reverse transcriptase-infected human myometrial cell line cells, with more extensive growth inhibition observed in PHM1s. In PHM1s, activin-A decreased oxytocin receptor and HoxA-10 mRNA expression but did not alter total progesterone receptor, cyclooxygenase-2 (Cox-2), and connexin 43 mRNA expression levels. Furthermore, treatment of PHM1 myometrial cells with activin-A attenuated oxytocin and thromboxaneA2 induced intracellular Ca(2+) accumulation. In conclusion, myometrial cells are activin sensitive, and activin-A can regulate myometrial cell functions.
激活素是一种多效性生长因子，其组织分布广泛，包括生殖组织。虽然激活素在性腺和子宫组织中的直接作用已有描述，但在子宫肌层中的作用尚未明确。在本研究中，我们已对子宫组织和子宫肌层细胞系对激活素 -A 的反应特性进行了表征。子宫组织以及两种子宫肌层细胞系，即 PHM1（妊娠人类子宫肌层 1）和 hTERT HM（端粒酶逆转录酶感染的人类子宫肌层），通过 Smad-2 的磷酸化来衡量，对激活素 -A 有反应。这些细胞系表达完整的激活素受体以及激活素β(A)亚基和卵泡抑素。激活素抑制了 PHM1 和端粒酶逆转录酶感染的人类子宫肌层细胞系细胞的增殖，在 PHM1 中观察到更广泛的生长抑制。在 PHM1 中，激活素 -A 降低了催产素受体和 HoxA-10 mRNA 的表达，但未改变总孕酮受体、环氧合酶 -2（Cox-2）和连接蛋白 43 mRNA 的表达水平。此外，用激活素 -A 处理 PHM1 子宫肌层细胞可减弱催产素和血栓素 A2 诱导的细胞内 Ca(2+)积累。总之，子宫肌层细胞对激活素敏感，且激活素 -A 可调节子宫肌层细胞功能。
