Prolactin as a candidate sebotrop(h)ic hormone?

Abstract

Recognised for its key role in lactation, it is less well appreciated that the neurohormone prolactin (PRL) is actually one of the most pleiotropic hormones known. Not only does PRL exert both tropic and trophic effects in a wide range of tissues, but it is also expressed in human skin and hair follicles and regulates multiple complex cutaneous functions, including keratin expression and hair growth. Despite several clinical indications that PRL may also play a role in sebaceous gland (SG) biology, the effects of PRL on SG function have received little attention. In this Viewpoint essay, we argue that PRL may be a sebotrop(h)ic hormone and could represent a novel therapeutic target in human dermatoses affecting the SG. We provide preliminary evidence in support of this hypothesis (based on findings in human skin organ culture) and chart the major open questions in SG biology and pathology from a PRL research perspective. We close by delineating how these questions can be experimentally addressed so as to identify new therapeutic strategies that are either sebogenic or sebostatic, for example in the management of acne and cutaneous ageing.

Seborrheic dermatitis—Looking beyond Malassezia

“…There is strong evidence that neuroendocrine activities influence both the sebaceous gland and SD occurrence. For example patients with hyperprolactinemia with increased blood androgen levels more frequently develop SD, which supports the regulation of sebaceous activity by prolactin . SD is also associated with many neurologic and psychiatric conditions, including Parkinson Disease (PD), Alzheimer's disease, syringomyelia, epilepsy, cerebrovascular infarcts, postencephalitis, mental retardation, poliomyelitis, traumatic brain injury, spinal cord injury, trigeminal nerve injury and other facial nerve palsies .…”

“…Such murine in vivo studies and traditional immunohistology and gene expression analyses of SD patient biopsies can be optimally complemented by ex vivo assays, such as organ‐cultured human scalp skin, which allow for experimental interrogation . These ex vivo assays will also be instrumental for testing novel treatment principles before these are explored in controlled clinical trials, for example in order to probe whether epidermal barrier restoration ameliorates symptoms and prevents SD recurrence after antifungal treatment.…”

Neuroendocrinology and neurobiology of sebaceous glands

“…These observations suggest that, in the context of sebum production, the main function of PRL might be to sensitise SGs to stimulation by androgens (Fig. ), perhaps by upregulating expression of androgen‐metabolising enzymes (Langan, Hinde & Paus, ). Indeed, PRL is known to regulate the activity of 5α‐reductase peripherally, namely in the reproductive organs, but in this context, PRL appears to inhibit 5α‐reductase (Yamanaka et al ., ; Noci et al ., ; Serafini & Lobo, ).…”

“…), which serves as proof‐of‐principle that PRL can act directly on cutaneous appendages. Furthermore, a recent study, utilising full‐thickness human skin cultured ex vivo , has provided preliminary evidence that PRL increases the size and lipid content of SGs, and also stimulates proliferation of peripheral sebocytes (Langan, Hinde & Paus, ). These effects of PRL could be ameliorated using a mutant form of human PRL (Δ1–9‐G129R‐hPRL) as a competitive PRL‐R antagonist (Langan, Hinde & Paus, ).…”

“…Experimentally, the use of short‐term ex vivo SG culture systems could be readily exploited to dissect the contribution of intra‐cutaneous PRL production versus systemic PRL in the regulation of SG physiology, as well as to identify any sex‐dependent effects (Langan, ; Langan, Hinde & Paus, ). This would remove the influence of ill‐defined serum‐derived endocrine factors, thus allowing for the drawing of more definitive conclusions regarding the role of PRL.…”