Abstract
11 min readLetter to the EditorUtilizing the hair follicle to dissect the regulation and autocrine/paracrine activities of prolactin in humansEwan A. Langan, Christopher E. M. Griffiths, and Ralf PausEwan A. LanganDermatology Centre, Salford Royal National Health Service Foundation Trust, School of Translational Medicine, The University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom; and Department of Dermatology, University of Lübeck, D-23538, Lübeck, Germany, Christopher E. M. GriffithsDermatology Centre, Salford Royal National Health Service Foundation Trust, School of Translational Medicine, The University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom; and , and Ralf PausDermatology Centre, Salford Royal National Health Service Foundation Trust, School of Translational Medicine, The University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom; and Department of Dermatology, University of Lübeck, D-23538, Lübeck, GermanyPublished Online:15 May 2012https://doi.org/10.1152/ajpendo.00080.2012MoreSectionsPDF (39 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations to the editor: Ferraris et al. (4) have recently reported an increase in anterior pituitary cell proliferation in Δ1-9-G129R-hPRL (competitive prolactin receptor antagonist) -expressing transgenic mice compared to wild-type controls. In addition, they reported increased proliferation/decreased apoptosis in primary rat anterior pituitary cell cultures and somatolactotroph GH3 cells treated with Δ1-9-G129R-hPRL, concluding that prolactin (PRL) is an "autocrine/paracrine antiproliferative/proapoptotic factor in the anterior pituitary".As Ferraris et al. acknowledge, their findings contrast with the well-documented proproliferative effects of PRL that have previously been reported in several tissue sites and cell populations, including keratinocytes (9), thymic epithelial cells (3), lymphoid cells (19), and prostate (18) and mammary gland epithelial cells (10). However, most of the cited studies varied considerably in the methodology they employed, including PRL dose (physiological vs. pharmacological), species (1, 6), tissue site (5, 18), and sex (14) investigated. Moreover, the lack of a human pituitary cell line (1), the absence of functional dopamine-2 receptors on GH3 cells (1), and the inherent difficulties in extrapolating results from rodent studies to humans (1) complicate attempts to understand the autocrine/paracrine actions of PRL. Therefore, the question of whether PRL promotes growth and suppresses apoptosis in well-defined primary human cell populations in situ remains essentially unresolved.However, the discovery that PRL is produced in several extrapituitary sites in humans has provided new opportunities for studying the local autocrine/paracrine actions of PRL. Indeed, the concept that PRL receptor (PRLR) stimulation exerts antiproliferative and proapoptotic effects (4) in humans is supported by evidence that PRL inhibits the growth of organ-cultured male human scalp hair follicles (HFs) and exerts proapoptotic/antiproliferative effects on male human hair matrix keratinocytes in situ (5).Traditionally, it is accepted that the regulation of pituitary and extrapituitary PRL production differs. This was based on the existence of the human superdistal extrapituitary PRL promoter (8), 5.8 kb upstream of the pituitary promoter, and the lack of dopaminergic inhibition of PRL production in extrapituitary sites (11). Yet, recent evidence challenges this assumption, since human adipocytes express functional dopamine receptors, whose stimulation inhibits PRL gene expression and PRL release by adipocytes (2). Moreover, both estrogen and thyrotropin-releasing hormone stimulate PRL mRNA and protein expression in situ in organ-cultured human scalp skin and/or HFs (15, 16), mimicking their regulation of pituitary PRL expression. Therefore, the regulation of PRL synthesis and release in the pituitary and in extrapituitary sites may share at least some regulatory principles and mechanisms, just as Ferraris et al. demonstrate functional similarities in the proliferation/apoptosis response of pituitary cells (4) vs. HF keratinocytes in situ (5).Accepting that the regulation of extrapituitary PRL expression can be established only in appropriate human models (1), we would like to draw attention to the fact that the serum-free organ culture of readily available, microdissected human HFs (12) provides an informative model in which to delineate both the regulation of PRL expression and the cytokine-like, growth-modulatory actions of PRL in the human system and in situ. Not only are human scalp HFs now appreciated to be both a target and a source of extrapituitary PRL expression (5, 15), but PRL is also a potent neuroendocrine regulator of 1) human HF growth (5), potentially in a sex- and site-specific manner (14); 2) selected keratin expression (17); and 3) adult human epithelial progenitor cells (17). Indeed, several of these effects can be reversed by the Δ1-9-G129R-hPRL (14, 17). Therefore, this model could also help address Ferraris et al.'s concern that endogenous PRL may "hamper" the determination of the actions of exogenously added PRL (4). In addition, since gene silencing is possible in intact, cultured human HFs (21), PRL and PRLR knockdown may be employed to further dissect the contribution of a endogenous PRL.One remaining uncertainty in terms of the human HF is the presence or absence of dopamine receptors and the effect of dopamine on follicular PRL synthesis and release. Dopamine receptors 2 (D2R) and 4 have been identified in murine skin (7), where they play an important role in epidermal barrier homeostasis, whereas D2R antagonists improve cutaneous wound healing by inducing angiogenesis (20). This provides sufficient encouragement to study dopamine receptor expression in human skin and HFs and to dissect whether they regulate human intracutaneous/intrafollicular PRL synthesis and/or secretion.In summary, female human HFs share at least some of the controls of pituitary PRL and PRLR expression (13, 15), and the antiproliferative/proapoptotic effect of PRL in pituitary cells is recapitulated in male HFs (4, 5). Therefore, human HF organ culture may, if interpreted with caution, serve as an instructive, physiologically and clinically relevant surrogate model in which the regulation and autocrine/paracrine activities of PRL in the human pituitary gland can be dissected in situ.GRANTSE.A. Langan is supported by a Medical Research Council Clinical Research Training Fellowship No. G0901988.DISCLOSURESNo conflicts of interest, financial or otherwise, are declared by the author(s).AUTHOR CONTRIBUTIONSAuthor contributions: E.A.L. drafted manuscript; E.A.L., C.G., and R.P. edited and revised manuscript; E.A.L., C.G., and R.P. approved final version of manuscript.REFERENCES1. Ben-Jonathan N , LaPensee CR , LaPensee EW. What can we learn from rodents about prolactin in humans? Endocr Rev 29: 1–41, 2008.Crossref | PubMed | ISI | Google Scholar2. Borcherding DC , Hugo ER , Idelman G , De Silva A , Richtand NW , Loftus J , Ben-Jonathan N. Dopamine receptors in human adipocytes: expression and functions. PLoS One 6: e25537, 2011.Crossref | PubMed | ISI | Google Scholar3. De Mello-Coelho V , Savino W , Postel-Vinay MC , Dardenne M. Role of prolactin and growth hormone on thymus physiology. Dev Immunol 6: 317–323, 1998.Crossref | PubMed | Google Scholar4. 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J Allergy Clin Immunol 129: 726–738, 2012.Crossref | PubMed | ISI | Google ScholarAUTHOR NOTESAddress for reprint requests and other correspondence: E. A. Langan, Dermatology Centre, Salford Royal NHS Foundation Trust, School of Translational Medicine, Univ. of Manchester, Manchester Academic Health Science Centre, Manchester, UK (e-mail: ewan.[email protected]ac.uk). Download PDF Previous Back to Top FiguresReferencesRelatedInformation CollectionsAJP-Endo CollectionsLipid, Lipoprotein, and Fatty Acid MetabolismNeuroendocrinology Cited ByDeciphering the molecular morphology of the human hair cycle: Wnt signalling during the telogen–anagen transformation29 September 2019 | British Journal of Dermatology, Vol. 182, No. 5Neuroendocrine Controls of Keratin Expression in Human Skin19 December 2018Is prolactin a negative neuroendocrine regulator of human skin re-epithelisation after wounding?22 September 2018 | Archives of Dermatological Research, Vol. 310, No. 10Prolactin as a candidate sebotrop(h)ic hormone?28 June 2018 | Experimental Dermatology, Vol. 27, No. 7Exploring the "brain-skin connection": Leads and lessons from the hair follicleCurrent Research in Translational Medicine, Vol. 64, No. 4Autocrine/paracrine roles of extrapituitary growth hormone and prolactin in health and disease: An overviewGeneral and Comparative Endocrinology, Vol. 220Neuroendocrinology of the hair follicle: principles and clinical perspectivesTrends in Molecular Medicine, Vol. 20, No. 10Harnessing neuroendocrine controls of keratin expression: A new therapeutic strategy for skin diseases?13 May 2014 | BioEssays, Vol. 36, No. 7Tumour Necrosis Factor Alpha, Interferon Gamma and Substance P Are Novel Modulators of Extrapituitary Prolactin Expression in Human Skin23 April 2013 | PLoS ONE, Vol. 8, No. 4 More from this issue > Volume 302Issue 10May 2012Pages E1311-E1312 Copyright & PermissionsCopyright © 2012 the American Physiological Societyhttps://doi.org/10.1152/ajpendo.00080.2012PubMed22589417History Received 14 February 2012 Accepted 16 February 2012 Published online 15 May 2012 Published in print 15 May 2012 Metrics
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