Cause of Failure of Lactation in Mouse Mammary Tumor Virus/Human Transforming Growth Factor α Transgenic Mice

Abstract

Abstract

Transgenic female mice bearing human transforming growth factor-α (TGFα) cDNA under the control of the mouse mammary tumor virus enhancer/promoter became pregnant but failed lactation. TGFα 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 TGFα transgenic (TGFα[+]) mice was small and its amount was comparable to that in the TGFα negative (TGFα[-]) mice. On the day of parturition, prolactin binding in TGFα(+) mice increased approximately 1.9-fold (insignificant), while that in TGFα(-) mice elevated over 5.3-fold (P < 0.01). The binding sites per cell were also higher in TGFα(-) mice. Radioimmunoassay of prolactin suggested that in TGFα(+) mice the low level of prolactin binding after parturition was not due to masking effect of serum prolactin. Among six TGFα(+) 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 TGFα(+) mice is principally due to the lack of elevation of mammary prolactin receptor after parturition. At present, the role of TGFα in this process is obscure; however, TGFα was revealed not to interfere with the binding of prolactin to the receptor.