Transcriptional and spatiotemporal regulation of prolactin receptor mRNA and cooperativity with progesterone receptor function during ductal branch growth in the mammary gland

Ductal branching within the mammary gland is stimulated by prolactin (PRL) and progesterone (P) acting through their receptors (PRLR and PR). Analysis of mammary gland PRLR expression revealed increasing expression of the lon g form (L-PRLR) and two of the three short forms (S1- and S3-PRLR) during p uberty that became maximal late in pubescence and early gestation, then dec lined during gestation. By contrast, S2-PRLR mRNA levels remained constant. Examination of stromal PRLR revealed the consistent expression of L-PRLR m RNA. By contrast, S1-PRLR was present only in the mammary fat pad of neonat es, whereas high neonatal expression of S2-PRLR became undetectable during puberty. Stromal expression of S3-PRLR decreased to low levels during puber ty and was undetectable during lactation and involution. Exogenous PRL stim ulated DNA synthesis in both epithelial and adjacent stromal cells in vivo. Distribution of PRLR mRNA in mammary epithelium was homogeneous before pub erty, and heterogeneous during puberty, gestation, and early lactation. A m utual role for PRLR and PR was suggested wherein PR mRNA increased beyond 6 weeks to maximal levels during puberty and gestation then became undetecta ble during lactation. In situ hybridization revealed that PR mRNA distribut ion is homogeneous in the ductal epithelium before 6 weeks and heterogenous during puberty and gestation and that PRLR and PR are similarly distribute d in the ductal epithelium. Neither hormone stimulated DNA synthesis in mam mary glands of ovariectomized females while their effects interacted marked ly. These results demonstrate differential PRLR transcription by epithelial and stromal cells and a. similar distribution of PRLR and PR that may faci litate the interaction between P and PRL during ductal branching in the Mam mary gland. Published 2001 Wiley-Liss, Inc.