Submitted to: Journal of Endocrinology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/28/2009
Publication Date: 4/28/2009
Citation: Trott, J.F., Horigan, K.C., Gloviczki, J.M., Costa, K.M., Freking, B.A., Farmer, C., Hayashi, K., Spencer, T., Morabito, J.E., Hovey, R.C. 2009. Tissue-specific Regulation of Porcine Prolactin Receptor Expression by Estrogen, Progesterone and Prolactin. Journal of Endocrinology. 202:153-166.
Interpretive Summary: Improving sow lactation performance using management tools or different nutritional strategies is a relevant issue to the current swine industry. A better understanding of endocrine factors involved and how they are regulated during mammary gland development is needed. The polypeptide hormone prolactin (PRL) regulates numerous physiological functions across multiple species. In pigs, PRL exerts its most significant effects on mammary gland growth, lactation and reproduction while also influencing stress response and maternal behavior. It is known that PRL plays a crucial role in regulating mammary gland growth and optimal lactation, where inadequate milk production can impair the pre- and post-weaning growth of piglets. We have generated a comprehensive analysis of the tissue- and stage-specific expression profiles and regulation of PRL and its receptor (PRLR) in various tissues of the pig. We tested the hypothesis that a local autocrine/paracrine PRL-PRLR loop plays a role in PRL regulated physiology in pigs. Developmentally- and hormonally-regulated PRLR levels in both the mammary gland and endometrium, but not in the kidney or liver were found. Expression of PRLR in the mammary gland and uterus during various stages of development appears to be coordinately and differentially regulated by the endocrine environment. At the same time, other tissues (liver and kidney) remained insensitive to these signals. In contrast, PRL mRNA levels were not developmentally regulated in any tissue except the pituitary. In situ hybridization analysis revealed the novel finding that PRL induced the expression of PRLR mRNA primarily in the stromal compartment of the mammary gland; whereas, estrogen induced its expression specifically in the mammary epithelium. These data provide the first profile of PRL gene expression in a range of PRL-responsive tissues during gestation for any species and contribute to a better understanding of mammary gland development and function in the pig.
Technical Abstract: Prolactin (PRL) acts through its receptor (PRLR) via both endocrine and local paracrine/autocrine pathways to regulate biological processes including reproduction and lactation. We analyzed the tissue and stage of gestation-specific regulation of PRL and PRLR expression in various tissues of pigs. Abundance of pPRLR-long form (LF) mRNA increased in the mammary gland and endometrium during gestation while in other tissues it remained constant. Abundance of the pPRLR-LF protein in mammary gland and endometrium also increased during gestation. We determined the hormonal regulation of pPRLR-LF mRNA expression in various tissues from ovariectomized, hypoprolactinemic gilts given combinations of the replacement hormones estrogen (E), progestin (P) and/or haloperidol-induced PRL. Abundance of pPRLR-LF mRNA in kidney and liver was unaffected by hormone treatments. Expression of uterine pPRLR-LF mRNA was induced by E; whereas, the effect of E was abolished by co12 administering P. The expression of pPRLR-LF mRNA in the mammary gland stroma was induced by PRL; whereas, E induced its expression in the epithelium. In contrast to these changes in pPRLR expression, pPRL expression was relatively constant and low during gestation in all tissues except the pituitary. Although pPRL could be cleaved by both cathepsin D and thrombin to release 16K PRL, no 16K PRL was detected within the mammary gland. Taken together, these data reveal that specific combinations of E, P and PRL differentially regulated pPRLR-LF expression in the endometrium and mammary gland, and that the action of PRL on its target tissues is more dependent upon pPRLR-LF abundance than local PRL expression.