Sakai S, Mizuno M, Harigaya T, Yamamoto K, Mori T, Coffey R J, Nagasawa H
Department of Animal Breeding, Faculty of Agriculture, University of Tokyo.
Proc Soc Exp Biol Med. 1994 Mar;205(3):236-42. doi: 10.3181/00379727-205-43702.
Transgenic female mice bearing human transforming growth factor-alpha (TGF alpha) cDNA under the control of the mouse mammary tumor virus enhancer/promoter became pregnant but failed lactation. TGF alpha mRNA was detected in the mammary glands of these mice by the reverse transcriptase-polymerase chain reaction. By the use of collagenase-dissociated mammary epithelial cells, the binding of prolactin to its receptor was determined before and after parturition. At the end of pregnancy, the binding in TGF alpha transgenic (TGF alpha [+]) mice was small and its amount was comparable to that in the TGF alpha negative (TGF alpha [-]) mice. On the day of parturition, prolactin binding in TGF alpha (+) mice increased approximately 1.9-fold (insignificant), while that in TGF alpha (-) mice elevated over 5.3-fold (P < 0.01). The binding sites per cell were also higher in TGF alpha (-)mice. Radioimmunoassay of prolactin suggested that in TGF alpha (+) mice the low level of prolactin binding after parturition was not due to masking effect of serum prolactin. Among six TGF alpha (+) mice assayed, one mother with the highest prolactin binding activity (3.7-fold increase) initiated lactation, but the others did not. As there was little difference between groups in the growth and synthesis in the mammary glands, it was concluded that the failure of lactation in TGF alpha (+) mice is principally due to the lack of elevation of mammary prolactin receptor after parturition. At present, the role of TGF alpha in this process is obscure; however, TGF alpha was revealed not to interfere with the binding of prolactin to the receptor.
携带在小鼠乳腺肿瘤病毒增强子/启动子控制下的人转化生长因子α（TGFα）cDNA的转基因雌性小鼠能够怀孕，但泌乳失败。通过逆转录聚合酶链反应在这些小鼠的乳腺中检测到了TGFα mRNA。利用胶原酶解离的乳腺上皮细胞，测定了分娩前后催乳素与其受体的结合情况。在妊娠末期，TGFα转基因（TGFα[+]）小鼠中的结合量很小，其数量与TGFα阴性（TGFα[-]）小鼠中的相当。在分娩当天，TGFα（+）小鼠中的催乳素结合增加了约1.9倍（无统计学意义），而TGFα（-）小鼠中的增加超过5.3倍（P<0.01）。TGFα（-）小鼠中每个细胞的结合位点也更高。催乳素的放射免疫分析表明，在TGFα（+）小鼠中，分娩后催乳素结合水平低不是由于血清催乳素的掩盖作用。在测定的6只TGFα（+）小鼠中，一只催乳素结合活性最高（增加3.7倍）的母鼠开始泌乳，但其他母鼠没有。由于各组在乳腺生长和合成方面差异不大，得出结论：TGFα（+）小鼠泌乳失败主要是由于分娩后乳腺催乳素受体缺乏升高。目前，TGFα在此过程中的作用尚不清楚；然而，已发现TGFα不会干扰催乳素与受体的结合。
