Sexual Hormones in Human Skin

Zouboulis, Christos C.; Chen, W.-C.; Thornton, M. Julie; Qin, Kenan; Rosenfield, RobertL

doi:10.1055/s-2007-961807

Cited by 324 publications

(265 citation statements)

References 173 publications

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“…This study is not only consistent with previous work describing human skin as both a hormone target and an endocrine gland (20)(21)(22)40), but establishes that early passage (P3) primary cultures of human dermal fibroblasts and epidermal keratinocytes retain in culture the key steroidogenic proteins seen in whole skin biopsies that are required for the conversion of cholesterol to potent androgens and estrogens (Fig. 1).…”

Section: Discussionsupporting

confidence: 79%

“…However, the complex pathways of steroid intracrinology and regulation of receptor expression in human skin are still poorly understood. Although the presence of AR, ERa, and ERb in human skin is well established (11,(19)(20)(21)(22), there is increasing evidence that rapid, nongenomic estrogen signaling is mediated by GPR30, also known as GPER1 (23)(24)(25), yet its expression in adult human skin has not been reported. The first aim of this study was to determine whether early passage (P3) primary cultures of human skin dermal fibroblasts and epidermal keratinocytes, the key mesenchymal and epithelial cells in the skin, retain the vital steroidogenic machinery required for the conversion of cholesterol to potent androgens and estrogens and therefore would be relevant in vitro models for functional studies of steroid hormone action.…”

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confidence: 99%

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Intracrine sex steroid synthesis and signaling in human epidermal keratinocytes and dermal fibroblasts

Pomari

Valle

Pertile³

et al. 2014

FASEB j.

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Peripheral intracrine sex steroid synthesis from adrenal precursors dehydroepiandrosterone (DHEA) and DHEA-sulfate has evolved in humans. We sought to establish if there are differences in intracrine, paracrine, and endocrine regulation of sex steroids by primary cultures of human skin epidermal keratinocytes and dermal fibroblasts. Microarray analysis identified multifunctional genes modulated by steroids, quantitative RT-PCR (qRT-PCR) mRNA expression, enzymatic assay aromatase activity, scratch assay cell migration, immunocytochemistry a-smooth muscle actin (a-SMA), and collagen gel fibroblast contraction. All steroidogenic components were present, although only keratinocytes expressed the organic anion organic anion transporter protein (OATP) 2B1 transporter. Both expressed the G-protein-coupled estrogen receptor (GPER1). Steroids modulated multifunctional genes, up-regulating genes important in repair and aging [angiopoietin-like 4 (ANGPTL4), chemokine (C-X-C motif) ligand 1 (CXCL1), lamin B1 (LMNB1), and thioredoxin interacting protein (TXNIP)]. DHEA-sulfate (DHEA-S), DHEA, and 17b-estradiol stimulated keratinocyte and fibroblast migration at early (4 h) and late (24-48 h) time points, suggesting involvement of genomic and nongenomic signaling. Migration was blocked by aromatase and steroid sulfatase (STS) inhibitors confirming intracrine synthesis to estrogen. Testosterone had little effect, implying it is not an intermediate. Steroids stimulated fibroblast contraction but not a-SMA expression. Mechanical wounding reduced fibroblast aromatase activity but increased keratinocyte activity, amplifying the bioavailability of intracellular estrogen. Cultured fibroblasts and keratinocytes provide a biologically relevant model system to investigate the complex pathways of sex steroid intracrinology in human skin.-Pomari, E., Valle, L. D., Pertile, P., Colombo, L., and Thornton, M. J. Intracrine sex steroid synthesis and signaling in human epidermal keratinocytes and dermal fibroblasts. FASEB J. 29, 508-524 (2015). www.fasebj.org

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Section: Discussionsupporting

confidence: 79%

mentioning

confidence: 99%

Intracrine sex steroid synthesis and signaling in human epidermal keratinocytes and dermal fibroblasts

Pomari

Valle

Pertile³

et al. 2014

FASEB j.

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“…HF immune privilege, connective tissue sheath (CTS) mast cell degranulation. (see Arck et al, 2005a; Bodó et al, 2005 and2007; Botchkarev et al, 2004; Colombe et al., 2007; Deplewski and Rosenfield, 2000;Hasse et al, 2007; Kauser et al, 2006;Ohnemus et al, 2006;Paus et al, 2006;Peters et al, 2006b and2007;Philp et al, 2004;Slominski et al, 2007;Telek et al, 2007;Zouboulis et al, 2007) While this remains to be conclusively demonstrated, it is likely that HFeSC are fully integrated into this neuroendocrine tapestry of general HF biology. However, all we have to go by currently are some pointers to potentially important elements in the as yet obscure neuroendocrinology of HFeSC.…”

Section: Page 4 Of 38mentioning

confidence: 99%

(Neuro-)endocrinology of epithelial hair follicle stem cells

Paus

Arck

Tiede

2008

Molecular and Cellular Endocrinology

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The hair follicle is a repository of different types of somatic stem cells. However, even though the hair follicle is both a prominent target organ and a potent, non-classical site of production and/or metabolism of numerous polypetide-and steroid hormones, neuropeptides, neurotransmitters and neurotrophins, the (neuro-) endocrine controls of hair follicle epithelial stem cell (HFeSC) biology remain to be systematically explored.Focussing on HFeSCs, we attempt here to offer a "roadmap through terra incognita" by listing key open questions, by exploring endocrinologically relevant HFeSC gene profiling and mouse genomics data, and by sketching several clinically relevant pathways via which systemic and/or locally generated (neuro-)endocrine signals might impact on HFeSC. Exemplarily, we discuss e.g. the potential roles of glucocorticoid and vitamin D receptors, the hairless gene product, thymic hormones, bone morphogenic proteins (BMPs) and their antagonists, and Skg-3 in HFeSC biology. Furthermore, we elaborate on the potential role of nerve growth factor (NGF) and substance P-dependent neurogenic inflammation in HFeSC damage, and explore how neuroendocrine signals may influence the balance between maintenance and destruction of hair follicle immune privilege, which protects these stem cells and their progeny. These considerations call for a concerted research effort to dissect the (neuro)-endocrinology of HFeSCs much more systematically than before. The hair follicle (HF) and its special, associated mesenchyme (i.e. the connective tissue sheath, CTS) are repositories of different types of somatic stem cells (epithelial, mesenchymal, neural, mesenchymal) (Cotsarelis, 2006; Kruse et al., 2006;Millar, 2005;Ohyama et al., 2006;Tiede et al. 2007;Waters et al., 2007;Yu et al., 2006). These HFassociated stem cell populations are critical for HF development and function, including HF pigmentation (Nishimura et al., 2002(Nishimura et al., , 2005Sarin and Artandi, 2007). Fig. 1 shows several important, recognized hair follicle-associated stem cell populations and their bestcharacterized location(s) in the pilosebaceous unit, though it must be kept in mind that the indicated ones are unlikely to be the only stem cell population associated with mammalian skin appendages (Tiede et al. 2007). Clinical importance of hair follicle stem cellsHair follicle epithelial stem cells (HFeSCs) are clinically important, since they can be key targets for pathological processes, such as an autoaggressive inflammatory cell attack on HFeSC, e.g. in lupus erythematosus or lichen planopilaris, where the destruction of bulge HFeSCs (see Fig.1) abolishes the hair follicle's capacity to cycle and to rhythmically regenerate itself, leading to scarring alopecia (Cotsarelis, 2006;Hiroi et al., 2006;Mobini et al., 2005;Paus, 2006). Likewise, a gradual loss of HF melanocyte stem cells may exhaust the HF pigmentary unit's capacity to generate itself and to produce melanin and thus likely plays a key role in hair graying (Commo et al., 2004;...

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“…Androgens have long been known to play a key role in the development of acne [76,77], seborrhoea [75], hirsutism, and androgenic alopecia [78].…”

Section: The Role Of Androgen Biosynthesis Genes In the Pathogenesis mentioning

confidence: 99%

“…The pilosebaceous unit, an endocrine organ, is an important source of localized hormone production, but also a target of various hormones synthesized elsewhere in the human body [75].…”

Section: Polymorphisms Of Genes Playing a Role In The Steroid Hormonementioning

confidence: 99%

Studying the genetic predisposing factors in the pathogenesis of acne vulgaris

Szabó

Kemény

2011

Human Immunology

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A B S T R A C TAcne is one of the most common dermatologic diseases in the developed regions of the world, affecting a large percentage of the population. Despite the great improvement in the number and quality of studies of the molecular etiology of this disease in the past 3 decades, the detailed molecular pathogenesis and the cause of the large individual variations in severity of skin symptoms remain unknown. The roles of genetic inheritance and special genetic susceptibility and protective factors have been suggested for over 100 years, but their identification and determination started only in the 1990s. To date, only a small number of genetic polymorphisms affecting the expression and/or function of a handful of genes have been investigated. This review surveys the major findings of the classic and molecular genetic studies that have been conducted in this field, draws conclusions, and indicates how the available data help our current understanding of the pathogenesis of this common skin disease. ᭧

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Sexual Hormones in Human Skin

Cited by 324 publications

References 173 publications

Intracrine sex steroid synthesis and signaling in human epidermal keratinocytes and dermal fibroblasts

Intracrine sex steroid synthesis and signaling in human epidermal keratinocytes and dermal fibroblasts

(Neuro-)endocrinology of epithelial hair follicle stem cells

Studying the genetic predisposing factors in the pathogenesis of acne vulgaris

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