Growth Hormone and the Human Hair Follicle.

Elijah J Horesh,Jérémy Chéret,Ralf Paus

doi:10.3390/ijms222413205

Abstract

Ever since the discoveries that human hair follicles (HFs) display the functional peripheral equivalent of the hypothalamic-pituitary-adrenal axis, exhibit elements of the hypothalamic-pituitary-thyroid axis, and even generate melatonin and prolactin, human hair research has proven to be a treasure chest for the exploration of neurohormone functions. However, growth hormone (GH), one of the dominant neurohormones of human neuroendocrine physiology, remains to be fully explored in this context. This is interesting since it has long been appreciated clinically that excessive GH serum levels induce distinct human skin pathology. Acromegaly, or GH excess, is associated with hypertrichosis, excessive androgen-independent growth of body hair, and hirsutism in females, while dysfunctional GH receptor-mediated signaling (Laron syndrome) is associated with alopecia and prominent HF defects. The outer root sheath keratinocytes have recently been shown to express functional GH receptors. Furthermore, and contrary to its name, recombinant human GH is known to inhibit female human scalp HFs’ growth ex vivo, likely via stimulating the expression of the catagen-inducing growth factor, TGF-β2. These limited available data encourage one to systematically explore the largely uncharted role of GH in human HF biology to uncover nonclassical functions of this core neurohormone in human skin physiology.

Highlights

We argue that the limited available data encourages one to systematically dissect the role of growth hormone (GH) in human hair follicles (HFs) biology in order to uncover nonclassical functions of this core neurohormone in human skin physiology and to develop novel GH or GH receptor-targeting neuroendocrine strategies for the therapeutic manipulation of hair loss and unwanted hair growth
Acts on the GHRH receptor (GHRHR) in somatotropic cells of the anterior pituitary to release the HPS axis, Growth hormone-releasing hormone (GHRH) acts on the GHRHRs in somatotropic cells of the anterior pituitary to release systemically, which interacts with growth hormone receptor (GHR) systemically, including in the HF
Since GH influences the expression level of insulinlike growth factor 1 (IGF-1) and TGF-β2, it would be interesting to evaluate the impact of GH/GHR signaling on the hair follicle immune privilege as both growth factors are well-known immune privilege guardians

Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. The synthesis, secretion, and regulation of hormones of the hypothalamus-pituitary-adrenal (HPA) axis have been documented in human scalp HFs ex vivo. In the absence of systemic connections, cultured human scalp HFs express and respond to corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH), resulting in the HF synthesis of cortisol and activation of classical neuroendocrine feedback loops. All three POMC-derived peptides listed above regulate HF melanogenesis [4], while insufficient HF synthesis of melanotropic HPA axis hormones may contribute to HF greying [5]. We argue that the limited available data encourages one to systematically dissect the role of GH in human HF biology in order to uncover nonclassical functions of this core neurohormone in human skin physiology and to develop novel GH or GH receptor-targeting neuroendocrine strategies for the therapeutic manipulation of hair loss (effluvium, alopecia) and unwanted hair growth (hirsutism, hypertrichosis)

The Hypothalamus-Pituitary-Somatotropic Axis

Growth Hormone-Releasing Hormone

Insulin-like Growth Factor-1

Major Open Questions

Findings

Conclusions