670 Growth hormone-induced signaling as a novel, intrafollicular neuroendocrine control of human hair growth

Abstract

Growth hormone (GH) and activation of its receptor (GHR) promote cell growth, proliferation, differentiation and stem cell activation either directly or via the induction of IGF-1. While some clinical case reports suggest that human hair follicles (HFs) may be GH-responsive, it is unknown whether GH exerts any functions in human HF biology. To explore this we charted the expression of GH, GHR and GHRH (growth hormone releasing hormone), the hypothalamic neurohormone that stimulates pituitary GH expression and release, in human scalp HFs. So far, we have detected GH, GHR and GHRH protein expression in the ORS of human anagen VI HFs as well as in the sebaceous gland epithelium. qRT-PCR analysis revealed that human scalp HFs also transcribe GHR mRNA, supporting that human HFs are an extrapituitary source of GH production. qRT-PCR analysis showed that GHR transcription decreases during HF regression (catagen HFs). Interestingly, the level of GHR transcription was inversely correlated with that of the GH-inhibiting hormone, somatostatin (SST), whose expression increased in catagen HFs. Next, organ-cultured human scalp HFs were stimulated with recombinant hGH (rhGH, 50-100 ng/ml) or recombinant GH-binding protein (rGHBP), which can exert both GH-antagonistic and agonistic effects. hGH and GHBP both promoted hair shaft elongation and tended to inhibit catagen development ex vivo. qRT-PCR analysis showed that hGH (100 ng/ml) and GHBP (100 ng/ml) induced an increase in HF mRNA levels of JAK2, the downstream target after GHR activation, and of SST. While we are still investigating how GHR silencing in human HFs ex vivo impacts on standard hair biology read-out parameters, our pilot study already suggests that GHR-mediated signaling by intrafollicularly generated GH is as a major novel neuroendocrine regulator of human hair growth.