Multiple forms of prolactin receptor messenger ribonucleic acid are specifically expressed and regulated in murine tissues and the mammary cell line HC11.

The expression of PRL receptor mRNA in mouse tissues was studied. Seven PRL receptor transcripts of different sizes were found. The pattern of expression was tissue specific. The PRL receptor protein exists in isoforms of approximately 300 and 600 amino acids, which differ in the sequence and length of the cytoplasmic domain. Probes specific for the lower mol wt forms of the receptor hybridized to transcripts of 1.4, 2.4, 3.5, and 4.2 kilobases (kb), which were predominantly expressed in the liver and kidney. Among the three isoforms of the small form of the receptor, PR-3 was highly expressed, PR-2 was weakly expressed, and PR-1 was undetectable. Probes specific for the higher mol wt receptor form detected transcripts of 9 and 10 kb, expressed most strongly in the ovary, mammary gland, and kidney. An additional 8.3-kb transcript was expressed in the kidney. The PRL-responsive mouse mammary epithelial cell line HC11 expressed only the 9- and 10-kb receptor mRNAs, as did the mammary gland. The transcripts for the two PRL receptor forms were independently regulated during pregnancy and lactation in a tissue-specific manner. The expression of the small receptor form in the liver increased 7-fold during pregnancy and decreased during lactation. Its expression in the kidney remained constant. Expression of the larger receptor form increased 2.5-fold in the kidney during lactation, but remained constant in the mammary gland. In the ovary the expression of the large receptor form could be elevated 4-fold after induction of hyperovulation with FSH and hCG. Thus, in the mouse there are at least two forms of the PRL receptor regulated independently in different tissues.