Sexual hormones utilize complex mechanisms to modulate sebocyte differentiation

Zouboulis, C. C.; Chen, W.; Alestas, Theodosios; Makrantonaki, Evgenia; Seltmann, Holger; Müller‐Decker, Karin

doi:10.1111/j.0906-6705.2005.0266l.x

Cited by 9 publications

(6 citation statements)

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“…This is in good agreement with the ageing phenotype, because it is known that the number and the functionality of capillary structures decrease with age. 1 The exact molecular mechanismswere not addressed in the present study; however, our data indicate that the secretion of miR-126 is affected rather than its basal endogenous expression. In the literature, the participation of active secretory mechanisms for miRs has been reported via (A) exosome-mediated delivery of miRNAs via NSmase as suggested by Bang et al 7 in a model of crosstalk between cardiac cells or (B) mediated by Rab proteins emphasized in a recent study in endothelial cells.…”

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confidence: 70%

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Identification of miR‐126 as a new regulator of skin ageing

Fiedler

Grönniger

Pfanne

et al. 2017

Experimental Dermatology

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Movie S2 This is similar to movie 1, but with a more direct interaction. This is to indicate the heterogeneous nature of the nerve interactions with keratinocytes Movie S3 A 3-D resolution of nerve fiber innervation of keratinocytes showing synaptic bouton-like structure penetrating and exiting keratinocytes; corresponds to figure 2dMovie S4 A bottom to top Z projection of the sample from figure 2d and Movie 3, indicating that the nerve fiber could be within one or | QUESTIONS ADDRESSEDA deregulation of miR expression in skin-associated diseases such as psoriasis and atopic dermatitis has been reported previously. 4,5However, to our knowledge, no study has been published yet, showing that specific secretory miRs become deregulated in the course of skin ageing and are involved in human skin cell crosstalk. Thus, we analysed, if secreted miRs might play a role in age-related dysfunctions. | EXPERIMENTAL DESIGNWe generated miR profiles of interstitial fluid collected from younger and older volunteers after suction blistering and identified agedependent differences in miR levels (eg miR-126). In vitro, we analysed whether miR-126 is age-dependently secreted by dermal endothelial cells and incorporated by other skin cells. | RESULTS | Secretory miR levels during skin ageingTo investigate the levels of secreted miRs during skin ageing, human interstitial fluid of the skin was analysed. 6 Quantitative PCR-based microRNA profiling was performed, and 175 miRs were detected with a C t -value <40 which was sufficient to be considered in the following analysis ( Figure S1 and Table S1). Setting a threshold of 1.5-fold regulation (up/down), we identified 61 miRs that were regulated in an age-related manner in suction blister fluids collected from young and old volunteers. The results could be confirmed in an independent experiment for three selected miRs (miR-100, miR-126 and miR-223) | Age-related miR-100 , miR-126 and miR-223 levels in cultured endothelial cellsIn vitro analysis was performed to delineate whether the age-related miR expression changes are triggered during cellular ageing. We cultivated dermal endothelial cells isolated from volunteers aged between 22 and 73 years and determined miR-100, miR-126 and miR-223 abundance in the supernatant 48 hours after cell seeding. All three miRs were significantly decreased in the supernatant of endothelial cell populations isolated from aged volunteers compared to the younger cell population ( Figure S2A-C). In contrast, intra-cellular miR levels detected for miR-100 and miR-126 (miR-223 was not analysed) in the intra-cellular compartment remain stable throughout age ( Figure S3A-B).*contributed equally to this work F I G U R E 1 Age-related miR expression changes in human suction blister fluids of the skin. A-C: Different miRs were selected from miRNA profiling for validation from qRT-PCR profiling. The suction blister fluid of 20 healthy volunteers of two different age groups (18-28 years and 66-75 years) was collected, and the suction blister fluids of 2 volunteers ...

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confidence: 70%

“…This is in good agreement with the ageing phenotype, because it is known that the number and the functionality of capillary structures decrease with age. 1 The exact molecular mechanisms…”

Section: Discussionmentioning

confidence: 99%

Identification of miR‐126 as a new regulator of skin ageing

Fiedler

Grönniger

Pfanne

et al. 2017

Experimental Dermatology

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“…Under the stimulation of androgens, sebum has thermoregulatory and repelling properties (40). Androgens and peroxisome proliferators-activated receptor (PPAR) ligands as well as oestrogens and the complex insulin-like growth factor-I ⁄ insulin-like growth factor-I receptors modify lipid synthesis (41,42). On the other hand, the levels of squalene, another prominent sebaceous lipid, are decreased by antihistamines in vitro, whereas human sebocytes express histamine 1 receptors in vivo and (18,19,37) Highly complex acetylcholine receptor expression pattern (70) Preservation of characteristics of stem-like cells despite their terminal cell differentiation programme (47,48)…”

Section: The Sebaceous Gland and Its Functionsmentioning

confidence: 99%

Frontiers in sebaceous gland biology and pathology

Zouboulis

Baron

Böhm

et al. 2008

Experimental Dermatology

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The development of experimental models for the in vitro study of human sebaceous gland turned down the theory of a phylogenetic relict and led to the identification of several, unknown or disregarded functions of this organ. Such functions are the production of foetal vernix caseosa, the influence of three-dimensional organization of the skin surface lipids and the integrity of skin barrier and the influence on follicular differentiation. In addition, the sebaceous gland contributes to the transport of fat-soluble antioxidants from and to the skin surface, the natural photoprotection, the pro-and antiinflammatory skin properties and to the innate antimicrobial activity of the skin. It is mainly responsible for skin's independent endocrine function, the hormonally induced skin ageing process, the steroidogenic function of the skin as well as its thermoregulatory and repelling properties and for selective control of the hormonal and xenobiotical actions of the skin. Interestingly, sebocytes, at least in vitro, preserve characteristics of stem-like cells despite their programming for terminal differentiation. This review reports on various sebaceous gland functions, which are currently under investigation, including its role on the hypothalamus-pituitaryadrenal-like axis of the skin, the impact of acetylcholine on sebocyte biology, the activity of ectopeptidases as new targets to regulate sebocyte function, the effects of vitamin D on human sebocytes, the expression of retinoid metabolizing cytochrome P450 enzymes and the possible role of sebum as vehicle of fragrances. These multiple homeostatic functions award the sebaceous gland the role 'brain of the skin' and the most important cutaneous endocrine gland.

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“…Zouboulis et al (266) showed that, in sebocytes, the expression of peroxisome proliferator-activated receptor (PPAR) ␥, postulated to be required for androgen-induced lipogenesis, was down-regulated by the phytoestrogen genistein, whereas E2 enhanced the metabolism of prostaglandin D2 to ⌬12-prostaglandin J2, a natural PPAR␥ ligand. Additionally, the same group found that E2 increases IGF-I synthesis and down-regulates IGF-I receptor expression (266).…”

Section: Estrogen Target Genes In the Pilosebaceous Unitmentioning

confidence: 99%

The Hair Follicle as an Estrogen Target and Source

et al. 2006

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For many decades, androgens have dominated endocrine research in hair growth control. Androgen metabolism and the androgen receptor currently are the key targets for systemic, pharmacological hair growth control in clinical medicine. However, it has long been known that estrogens also profoundly alter hair follicle growth and cycling by binding to locally expressed high-affinity estrogen receptors (ERs). Besides altering the transcription of genes with estrogen-responsive elements, 17␤-estradiol (E2) also modifies androgen metabolism within distinct subunits of the pilosebaceous unit (i.e., hair follicle and sebaceous gland). The latter displays prominent aromatase activity, the key enzyme for androgen conversion to E2, and is both an estrogen source and target.Here, we chart the recent renaissance of estrogen research in hair research; explain why the hair follicle offers an ideal, clinically relevant test system for studying the role of sex steroids, their receptors, and interactions in neuroectodermal-mesodermal interaction systems in general; and illustrate how it can be exploited to identify novel functions and signaling cross talks of ER-mediated signaling. Emphasizing the long-underestimated complexity and species-, gender-, and site-dependence of E2-induced biological effects on the hair follicle, we explore targets for pharmacological intervention in clinically relevant hair cycle manipulation, ranging from androgenetic alopecia and hirsutism via telogen effluvium to chemotherapy-induced alopecia. While defining major open questions, unsolved clinical challenges, and particularly promising research avenues in this area, we argue that the time has come to pay estrogen-mediated signaling the full attention it deserves in future endocrinological therapy of common hair growth disorders. (Endocrine Reviews 27: 677-706, 2006)

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Sexual hormones utilize complex mechanisms to modulate sebocyte differentiation

Cited by 9 publications

References 0 publications

Identification of miR‐126 as a new regulator of skin ageing

Identification of miR‐126 as a new regulator of skin ageing

Frontiers in sebaceous gland biology and pathology

The Hair Follicle as an Estrogen Target and Source

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