Yamaguchi M, Ogren L, Kurachi H, Hirota K, Imai T, Talamantes F
Department of Biology, University of California, Santa Cruz 95064, USA.
Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2830-4. doi: 10.1073/pnas.92.7.2830.
This study was undertaken to determine whether transforming growth factor alpha (TGF-alpha) regulates the production of mouse placental lactogen I (mPL-I) and mPL-II in a manner that is similar to that of epidermal growth factor (EGF), which was previously shown to stimulate mPL-I secretion and inhibit mPL-II secretion. In contrast to the activity of EGF, human (h) and rat (r) TGF-alpha (each at 100 ng/ml) inhibited secretion of mPL-I by placental cells isolated from mice on day 7 of pregnancy. Maximum inhibition of mPL-I secretion occurred on the third day of a 5-day culture period and ranged between 37% and 56% in multiple trials. Incubation of cells with hTGF-alpha and EGF was not followed by a change in the mPL-I concentration of the medium, suggesting the peptides antagonized each other's effects. hTGF-alpha and rTGF-alpha inhibited secretion of mPL-II; maximum inhibition ranged between 62% and 84% in multiple trials. The lowest concentrations of hTGF-alpha that affected mPL-I and mPL-II secretion were 10 ng/ml and 1 ng/ml, respectively. EGF and hTGF-alpha bound to the same receptors on placental cells, as assessed by cross-linking, and both peptides stimulated receptor phosphorylation, as assessed by Western blot analysis. There are three types of mPL-containing cells in placental cultures: cells that contain only mPL-I, cells that contain only mPL-II, and cells that contain both mPLs. The percentage of each type of mPL-containing cell in the culture was determined by immunostaining. hTGF-alpha affected the differentiation of the subpopulations of PL-containing cells in a manner that differed from that of EGF. The data suggest that TGF-alpha and EGF do not regulate the production of mPL-I and mPL-II in a similar manner.
本研究旨在确定转化生长因子α（TGF-α）是否以类似于表皮生长因子（EGF）的方式调节小鼠胎盘催乳素I（mPL-I）和mPL-II的产生，此前已表明EGF可刺激mPL-I分泌并抑制mPL-II分泌。与EGF的活性相反，人（h）和大鼠（r）TGF-α（均为100 ng/ml）抑制了从妊娠第7天的小鼠分离的胎盘细胞分泌mPL-I。在为期5天的培养期的第三天，mPL-I分泌受到最大抑制，多次试验中抑制率在37%至56%之间。用hTGF-α和EGF孵育细胞后，培养基中mPL-I的浓度没有变化，表明这两种肽相互拮抗彼此的作用。hTGF-α和rTGF-α抑制mPL-II的分泌；多次试验中最大抑制率在62%至84%之间。影响mPL-I和mPL-II分泌的hTGF-α的最低浓度分别为10 ng/ml和1 ng/ml。通过交联评估，EGF和hTGF-α与胎盘细胞上的相同受体结合，通过蛋白质印迹分析评估，两种肽均刺激受体磷酸化。胎盘培养物中有三种含mPL的细胞类型：仅含mPL-I的细胞、仅含mPL-II的细胞以及同时含两种mPL的细胞。通过免疫染色确定培养物中每种含mPL细胞类型的百分比。hTGF-α影响含PL细胞亚群的分化，其方式与EGF不同。数据表明，TGF-α和EGF不以相似的方式调节mPL-I和mPL-II的产生。
