Thyrotropin releasing hormone (TRH): a new player in human hair‐growth control

Abstract

Thyrotropin-releasing hormone (TRH) is the most proximal component of the hypothalamic-pituitary-thyroid axis that regulates thyroid hormone synthesis. Since transcripts for members of this axis were detected in cultured normal human skin cells and since human hair follicles (HFs) respond to stimulation with thyrotropin, we now have studied whether human HF functions are also modulated by TRH. Here we report that the epithelium of normal human scalp HFs expresses not only TRH receptors (TRH-R) but also TRH itself at the gene and protein level. Stimulation of microdissected, organ-cultured HFs with TRH promotes hair-shaft elongation, prolongs the hair cycle growth phase (anagen), and antagonizes its termination by TGF-beta2. It also increases proliferation and inhibits apoptosis of hair matrix keratinocytes. These TRH effects may be mediated in part by reducing the ATM/Atr-dependent phosphorylation of p53. By microarray analysis, several differentially up- or down-regulated TRH-target genes were detected (e.g., selected keratins). Thus, human scalp HFs are both a source and a target of TRH, which operates as a potent hair-growth stimulator. Human HFs provide an excellent discovery tool for identifying and dissecting nonclassical functions of TRH and TRH-mediated signaling in situ, which emerge as novel players in human epithelial biology.

Association between polymorphisms in the TRHR gene, fat-free mass, and muscle strength in older women

“…The main consequence of this connection is the stimulation of secretion of thyroid-stimulating hormone. In response, the thyroid-stimulating hormone stimulates the release of thyroxine, which is important in developing skeletal muscle of vertebrates (Larsson et al 1994;Gáspár et al 2010). The study by Liu et al (2009) is pointed by the catalog of the National Human Genome Research Institute (Hindorff et al 2010) as the only work that found the association of TRHR gene and body mass (lean).…”

TSH is a novel neuroendocrine regulator of selected keratins in the human hair follicle

“…Therefore, we have asked whether TSH operates as a novel neuroendocrine regulator of human keratins in situ, using microdissected, organ-cultured human scalp HFs as a physiologically and clinically relevant assay systems [3][4][5]. This was complemented by studying the effect of TSH on keratin expression in cultured human outer root sheath (ORS) keratinocytes (KCs).Anagen VI HFs were isolated from normal frontotemporal scalp skin obtained after written informed consent from three healthy females undergoing routine face-lift surgery, as 3 previously described [4,5], adhering to Helsinki guidelines and under a licence from the ethics committee of the University of Lübeck. HF mRNA extracts from one female patient were subjected to quantitative real time PCR (qPCR) for selected hair keratin genes after 24 hrs treatment with TSH (100 mU ml -1 ) or vehicle.…”

“…The importance of the latter is highlighted by the recent discovery that the "pituitary" neuropeptide hormone, prolactin, which is also expressed by human HFs, potently regulates the expression of selected human keratins on the gene and protein level [3]. Moreover, microarray analyses had provided first clues that thyroid stimulating hormone (TSH) and its proximal regulator in the hypothalamic-pituitary-thyroid axis, thyrotropin-releasing hormone (TRH), might operate as previously unsuspected modulators of human hair keratin and KAP gene transcription in situ [4][5][6]. Also, we had recently found that TSH upregulates keratin K5 gene expression and protein synthesis as well as K14 transcription in human epidermis [4].…”

“…Also, we had recently found that TSH upregulates keratin K5 gene expression and protein synthesis as well as K14 transcription in human epidermis [4]. Therefore, we have asked whether TSH operates as a novel neuroendocrine regulator of human keratins in situ, using microdissected, organ-cultured human scalp HFs as a physiologically and clinically relevant assay systems [3][4][5]. This was complemented by studying the effect of TSH on keratin expression in cultured human outer root sheath (ORS) keratinocytes (KCs).…”

“…Anagen VI HFs were isolated from normal frontotemporal scalp skin obtained after written informed consent from three healthy females undergoing routine face-lift surgery, as previously described [4,5], adhering to Helsinki guidelines and under a licence from the ethics committee of the University of Lübeck. HF mRNA extracts from one female patient were subjected to quantitative real time PCR (qPCR) for selected hair keratin genes after 24 hrs treatment with TSH (100 mU ml -1 ) or vehicle.…”