Abstract
Corticotropin-releasing factor (CRF) signaling pathways are involved in the stress response, and there is growing evidence supporting hair growth inhibition of murine hair follicle in vivo upon stress exposure. We investigated whether the blockade of CRF receptors influences the development of hair loss in CRF over-expressing (OE)-mice that display phenotypes of Cushing's syndrome and chronic stress, including alopecia. The non-selective CRF receptors antagonist, astressin-B (5 µg/mouse) injected peripherally once a day for 5 days in 4–9 months old CRF-OE alopecic mice induced pigmentation and hair re-growth that was largely retained for over 4 months. In young CRF-OE mice, astressin-B prevented the development of alopecia that occurred in saline-treated mice. Histological examination indicated that alopecic CRF-OE mice had hair follicle atrophy and that astressin-B revived the hair follicle from the telogen to anagen phase. However, astressin-B did not show any effect on the elevated plasma corticosterone levels and the increased weights of adrenal glands and visceral fat in CRF-OE mice. The selective CRF2 receptor antagonist, astressin2-B had moderate effect on pigmentation, but not on hair re-growth. The commercial drug for alopecia, minoxidil only showed partial effect on hair re-growth. These data support the existence of a key molecular switching mechanism triggered by blocking peripheral CRF receptors with an antagonist to reset hair growth in a mouse model of alopecia associated with chronic stress.
Highlights
More than half a century ago, Hans Selye, the father of the stress concept in biology, stated that ‘‘an intense psychic shock may exert pronounced effects on the hair, e.g., graying and generalized loss of hair’’ [1]
Based on existing evidence that chronic stress impairs hair growth and that major components of the Corticotropinreleasing factor (CRF) system are expressed in the mouse and human skin [9,19], we investigated the ability of CRF receptor antagonists to influence hair loss/re-growth in CRF-OE mice
Saline injected ip in male CRF-OE mice did not have any effect on the alopecia: the skin color remained pink and no hair grew throughout the monitoring period (Figs. 1A and 2A, B)
Summary
More than half a century ago, Hans Selye, the father of the stress concept in biology, stated that ‘‘an intense psychic shock may exert pronounced effects on the hair, e.g., graying and generalized loss of hair’’ [1]. Subsequent cumulative experimental and clinical evidence indicates that chronic stress exerts a profound inhibitory effect on hair growth [2,3,4,5]. Corticotropinreleasing factor (CRF), adrenocorticotropic hormone (ACTH) and glucocorticoids are key components of the endocrine and neuroimmune responses to stress and they interrupt hair follicle growth cycle in humans and mice [2,3,6,7]. In cultured human scalp hair follicles, CRF up-regulates transcription of proopiomelanocortin (POMC) and immunoreactivity of ACTH and a-melanocyte-stimulating hormone (MSH), and increases cortisol secretion [5]. While a number of mouse mutants generated by targeting specific pathways involving hair follicle cycle resulted in nude mice or models of inflammatory alopecia [4,17,18], the CRF-OE mouse has not been examined so far as a model relevant to chronic stressinduced alopecia, despite an initial report that CRF-OE mice develop bilateral symmetric hair loss in adulthood [11]
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