Cause of failure of lactation in mouse mammary tumor virus/human transforming growth factor alpha transgenic mice.
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.
Sakai
S
S
Department of Animal Breeding, Faculty of Agriculture, University of Tokyo.
Mizuno
M
M
Harigaya
T
T
Yamamoto
K
K
Mori
T
T
Coffey
R J
RJ
Nagasawa
H
H
D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000032:analysis; D004702:Endocrine Glands / Q000033:anatomy & histology; D005260:Female; D006801:Humans; D007774:Lactation; D007785:Lactose / Q000032:analysis; D008297:Male; D008321:Mammary Glands, Animal / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009929:Organ Size; D011247:Pregnancy; D011388:Prolactin / Q000097:blood / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D011981:Receptors, Prolactin / Q000187:drug effects / Q000378:metabolism*; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D016211:Transforming Growth Factor alpha / Q000235:genetics / Q000502:physiology*
D012333:RNA, Messenger; D011981:Receptors, Prolactin; D016211:Transforming Growth Factor alpha; D011388:Prolactin; D004247:DNA; D007785:Lactose