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(American Journal of Pathology. 2006;168:748-756.)
© 2006 American Society for Investigative Pathology

Human Scalp Hair Follicles Are Both a Target and a Source of Prolactin, which Serves as an Autocrine and/or Paracrine Promoter of Apoptosis-Driven Hair Follicle Regression

Kerstin Foitzik*, Karoline Krause*, Franziska Conrad*, Motonobu Nakamura*{dagger}, Wolfang Funk{ddagger} and Ralf Paus*§

From the Department of Dermatology,* University Hospital Hamburg-Eppendorf, University of Hamburg, Hamburg, Germany; the Department of Dermatology,§ University Hospital Schleswig-Holstein, Campus Lübeck, University of Lübeck, Lübeck, Germany; Klinik Doctor Kozlowski,{ddagger} München, Germany; and Kyoto University,{dagger} Kyoto, Japan

The prototypic pituitary hormone prolactin (PRL) exerts a wide variety of bioregulatory effects in mammals and is also found in extrapituitary sites, including murine skin. Here, we show by reverse transcriptase-polymerase chain reaction and immunohistology that, contrary to a previous report, human skin and normal human scalp hair follicles (HFs), in particular, express both PRL and PRL receptors (PRL-R) at the mRNA and protein level. PRL and PRL-R immunoreactivity can be detected in the epithelium of human anagen VI HFs, while the HF mesenchyme is negative. During the HF transformation from growth (anagen) to apoptosis-driven regression (catagen), PRL and PRL-R immunoreactivity appear up-regulated. Treatment of organ-cultured human scalp HFs with high-dose PRL (400 ng/ml) results in a significant inhibition of hair shaft elongation and premature catagen development, along with reduced proliferation and increased apoptosis of hair bulb keratinocytes (Ki-67/terminal dUTP nick-end labeling immunohistomorphometry). This shows that PRL receptors, expressed in HFs, are functional and that human skin and human scalp HFs are both direct targets and sources of PRL. Our data suggest that PRL acts as an autocrine hair growth modulator with catagen-promoting functions and that the hair growth-inhibitory effects of PRL demonstrated here may underlie the as yet ill-understood hair loss in patients with hyper-prolactinemia.





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