Prolactin and the skin: a new frontier in the brain-skin axis

Psychological stress can trigger and/or worsen several common skin and hair diseases, for example, psoriasis and alopecia (hair loss). However the mechanisms by which this occurs are not fully understood. These diseases are associated with significant psychological and physical morbidity, and their impact on quality of life can be as severe as that of heart disease. Prolactin, a hormone produced in the brain and in the skin, is released in response to stress. Prolactin is associated with skin and hair diseases that are made worse by stress. I will investigate what controls the production of prolactin in the skin and in hair follicles. I will then measure the effect of a well validated, reproducible stress test on cutaneous prolactin production in healthy human volunteers. An in depth understanding of how prolactin mediates the effect of stress on the skin would represent a dramatic advance in our knowledge of how the mind affects the skin, and promises to identify new, much needed treatments for skin diseases which are triggered and/or worsened by stress. Newly discovered substances which can block the effects of prolactin may represent one such treatment.

Background: Many common, chronic skin diseases, including psoriasis, eczema and alopecia, are triggered and/or exacerbated by psychological stress. This link between the nervous, immune and cutaneous systems, the ?brain-skin axis,? is at the cutting edge of investigative dermatology, given the pressing need for new treatments to alleviate the substantial physical and psychological morbidity associated with these diseases. The novel discoveries that human skin and hair follicles are a potent source and target of prolactin (PRL), a pleiotropic stress response neurohormone traditionally associated with the anterior pituitary gland, and that several common skin diseases are associated with increased PRL expression, an entirely new frontier in the ?brain-skin axis? is emerging, which may shape our future understanding of the effect of stress on the skin in health and disease.
Hypotheses: Intracutaneous PRL and PRLR regulation differs from the regulation of PRL in the pituitary, and is affected by psychological stress.
Aims: To determine the regulation of intracutaneous PRL and PRLR production in healthy skin in vitro. To examine the response of intracutaneous PRL and PRLR to psychological stress in vivo. To identify therapeutic targets to manage stress-mediated skin disease.
Objectives: At the cellular and molecular levels I will investigate the mechanisms by which intracutaneous PRL and PRLR expression are regulated in healthy skin, gaining preclinical evidence that manipulating PRLR mediated signalling, using pure PRLR antagonists, will alter the cutaneous inflammatory milieu. This strategy is of central significance for inflammatory dermatoses, with potential beneficial effects on hair growth in vivo.
Design/Methods: I will utilise the skin and hair organ culture method to uncover the key regulators of PRL and PRLR expression and to examine the extent to which their effects on key parameters of hair follicle biology, and cytokine expression, result from PRLR mediated signalling. I will then examine the effect of psychological stress on intracutaneous PRL and PRLR expression in vivo, providing a potential therapeutic target in skin disease precipitated and/or aggravated by stress.
Scientific and Medical Opportunities: Understanding the regulation of intracutaneous PRL and PRLR expression, and how it is affected by psychological stress, promises to redefine our approach to the management of stress-mediated skin disease, an large area of unmet clinical need. Moreover, given that PRL is one of the most diverse bioregulators in mammalian biology, insights from this study may impact on our understanding of the role of PRL in tumorigenesis and immunoregulation, of key relevance to the skin.