title: Human hair follicles display a functional equivalent of the hypothalamic-pituitary-adrenal axis and synthesize cortisol.
abstract: The skin and its major appendages are prominent target organs and potent sources of key players along the classical hypothalamic-pituitary axis, such as corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and alpha melanocyte stimulating hormone (alpha-MSH), and even express key steroidogenic enzymes. Therefore, it may have established local stress response systems that resemble the hypothalamic-pituitary-adrenal (HPA) axis. However, functional evidence that this is indeed the case in normal human skin in situ has still been missing. We show that microdissected, organ-cultured human scalp hair follicles respond to CRH stimulation by up-regulating proopiomelanocortin (POMC) transcription and immunoreactivity (IR) for ACTH and alpha-MSH, which must have been processed from POMC. CRH, alpha-MSH, and ACTH also modulate expression of their cognate receptors (CRH-R1, MC1-R, MC2-R). In addition, the strongest stimulus for adrenal cortisol production, ACTH, also up-regulates cortisol-IR in the hair follicles. Isolated human hair follicles secrete substantial levels of cortisol into the culture medium, and this activity is further up-regulated by CRH. CRH also modulates important functional hair growth parameters in vitro (hair shaft elongation, catagen induction, hair keratinocyte proliferation, melanin production). Finally, human hair follicles display HPA axis-like regulatory feedback systems, since the glucocorticoid receptor agonist hydrocortisone down-regulates follicular CRH expression. Thus, even in the absence of endocrine, neural, or vascular systemic connections, normal human scalp hair follicles directly respond to CRH stimulation in a strikingly similar manner to what is seen in the classical HPA axis, including synthesis and secretion of cortisol and activation of prototypic neuroendocrine feedback loops.
authors.affiliation: Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Natsuho
authors.initials: N
authors.lastname: Ito
authors.forename: Taisuke
authors.initials: T
authors.lastname: Ito
authors.forename: Arno
authors.initials: A
authors.lastname: Kromminga
authors.forename: Albrecht
authors.initials: A
authors.lastname: Bettermann
authors.forename: Masahiro
authors.initials: M
authors.lastname: Takigawa
authors.forename: Frieder
authors.initials: F
authors.lastname: Kees
authors.forename: Rainer H
authors.initials: RH
authors.lastname: Straub
authors.forename: Ralf
authors.initials: R
authors.lastname: Paus
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000368:Aged; D001483:Base Sequence; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D025461:Feedback, Physiological; D005260:Female; D018859:Hair Follicle / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D006854:Hydrocortisone / Q000096:biosynthesis*; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009924:Organ Culture Techniques; D010913:Pituitary-Adrenal System / Q000502:physiology*; D011333:Pro-Opiomelanocortin / Q000235:genetics; D044102:Receptor, Melanocortin, Type 1 / Q000032:analysis; D018019:Receptors, Corticotropin-Releasing Hormone / Q000032:analysis; D000521:alpha-MSH / Q000494:pharmacology
chemical_list: D044102:Receptor, Melanocortin, Type 1; D018019:Receptors, Corticotropin-Releasing Hormone; D000521:alpha-MSH; D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone