Prolactin--a novel neuroendocrine regulator of human keratin expression in situ.

FASEB J. 2010 Jan 26.
Prolactin--a novel neuroendocrine regulator of human keratin expression in situ.

Ramot Dagger Tamas Biro Ddagger Stephan Tiede Balazs I Toth Ddagger Ewan A Langan Sect Koji Sugawara Kerstin Foitzik Arieh Ingber Dagger Vincent Goffin Paragraph Lutz Langbein Y, Paus R.

*Department of Dermatology, University of Lübeck, Lübeck, Germany;Department of Dermatology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel;Department of Physiology, University of Debrecen, Medical and Health Science Center, Research Center for Molecular Medicine, Debrecen, Hungary;Epithelial Sciences, School of Translational Medicine, University of Manchester, Manchester, UK;||Department of Dermatology, Children's Hospital Wilhelmstift, Hamburg, Germany; paragraph signINSERM, Unit 845, Research Center in Growth and Signaling, and University Paris Descartes, Faculty of Medicine, Necker Site, Paris, France; and#German Cancer Research Center, Genetics of Skin Carcinogenesis, Heidelberg, Germany.

The controls of human keratin expression in situ remain to be fully elucidated. Here, we have investigated the effects of the neurohormone prolactin (PRL) on keratin expression in a physiologically and clinically relevant test system: organ-cultured normal human hair follicles (HFs). Not only do HFs express a wide range of keratins, but they are also a source and target of PRL. Microarray analysis revealed that PRL differentially regulated a defined subset of keratins and keratin-associated proteins. Quantitative immunohistomorphometry and quantitative PCR confirmed that PRL up-regulated expression of keratins K5 and K14 and the epithelial stem cell-associated keratins K15 and K19 in organ-cultured HFs and/or isolated HF keratinocytes. PRL also up-regulated K15 promoter activity and K15 protein expression in situ, whereas it inhibited K6 and K31 expression. These regulatory effects were reversed by a pure competitive PRL receptor antagonist. Antagonist alone also modulated keratin expression, suggesting that "tonic stimulation" by endogenous PRL is required for normal expression levels of selected keratins. Therefore, our study identifies PRL as a major, clinically relevant, novel neuroendocrine regulator of both human keratin expression and human epithelial stem cell biology in situ.-Ramot, Y., Bíró, T., Tiede, S. Tóth, B. I., Langan, E. A., Sugawara, K., Foitzik, K., Ingber, A., Goffin, V., Langbein, L., Paus, R. Prolactin-a novel neuroendocrine regulator of human keratin expression in situ.