Androgens and androgen receptor action in skin and hair follicles

Ceruti, Julieta María; Leirós, Gustavo José; Balañá, María Eugenia

doi:10.1016/j.mce.2017.09.009

Cited by 143 publications

(166 citation statements)

References 163 publications

(182 reference statements)

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“…A parallel can be drawn with adipocyte differentiation, where Wnt signalling inhibits differentiation of preadipocytes, and is progressively downregulated as adipogenesis proceeds . Furthermore, activation of AR suppresses Wnt/β‐catenin signalling in the PSU and in SZ95 cells, and androgens are known to inhibit Wnt signalling in other tissues . Androgens may therefore promote sebocyte differentiation by downregulating Wnt signalling.…”

Section: Factors Controlling Sebaceous Gland Homeostasismentioning

confidence: 99%

“…121 Furthermore, activation of AR suppresses Wnt/b-catenin signalling in the PSU and in SZ95 cells, 135 and androgens are known to inhibit Wnt signalling in other tissues. 136 Androgens may therefore promote sebocyte differentiation by downregulating Wnt signalling. Conversely, LGR6 might suppress differentiation in peripheral sebocytes by promoting Wnt signalling through interaction with R-spondins.…”

Section: Peroxisome Proliferator-activated Receptor Cmentioning

confidence: 99%

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Homeostasis of the sebaceous gland and mechanisms of acne pathogenesis

et al. 2019

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Summary Background Sebaceous glands (SGs) are appendages of mammalian skin that produce a mixture of lipids known as sebum. Acne vulgaris is an exceptionally common skin condition, characterized by elevated sebum production, altered sebum composition, and the formation of infundibular cysts, called comedones. Comedo‐associated SGs are atrophic, suggesting that comedo formation involves abnormal differentiation of progenitor cells that generate the SG and infundibulum: the ‘comedo switch’. Understanding the biological processes that govern SG homeostasis promises to highlight potential aetiological mechanisms underlying acne and other SG‐associated skin disorders. Results In this review, we discuss the clinical data, genetic mouse models and in vitro research that have highlighted major hormones, paracrine factors, transcription factors and signalling pathways that control SG homeostasis. These include, but are not limited to androgens, progestogens and oestrogens; retinoids; receptor tyrosine kinases such as ErbB family receptors, fibroblast growth factor receptor 2 and insulin/insulin‐like growth factor 1 receptors; peroxisome proliferator‐activated receptor γ; aryl hydrocarbon receptor; and the Wnt signalling pathway. Where possible, the cellular and molecular mechanisms by which these regulatory factors control SG biology are indicated, along with considerations as to how they might contribute to acne pathogenesis. Conclusions Future research should seek to establish the relative importance, and causative relationships, of altered sebum production, sebum composition, inflammation and abnormal differentiation of sebaceous progenitors to the process of comedo formation in acne. Such an understanding will allow for therapeutic targeting of regulatory factors that control SG homeostasis, with the aim of treating acne.

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Section: Factors Controlling Sebaceous Gland Homeostasismentioning

confidence: 99%

Section: Peroxisome Proliferator-activated Receptor Cmentioning

confidence: 99%

Homeostasis of the sebaceous gland and mechanisms of acne pathogenesis

et al. 2019

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“…Also, systemic KTZ can suppress androgen production through inhibition of cytochrome P450‐dependent enzymes in the testes, ovaries and adrenal glands . It is conceivable that topical KTZ may possess a similar effect on the steroidogenesis function of the pilosebaceous units …”

Section: Discussionmentioning

confidence: 99%

“…13 It is conceivable that topical KTZ may possess a similar effect on the steroidogenesis function of the pilosebaceous units. 22 At the same time, KTZ could also affect lipase activity of Malassezia spp., 16 which has a higher lipase activity than C. acnes. 23 Some authors believed that Malassezia spp.…”

Section: Discussionmentioning

confidence: 99%

Topical 2% ketoconazole cream monotherapy significantly improves adult female acne: A double‐blind, randomized placebo‐controlled trial

Chottawornsak

Chongpison

Asawanonda

et al. 2019

The Journal of Dermatology

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The emergence of bacterial resistance is a global crisis. Prolonged use of antibiotics especially in acne is one issue of concern among dermatologists. Ketoconazole (KTZ) cream, a topical antifungal with anti‐inflammatory and antiandrogenic actions, can decrease lipase activity of Cutibacterium acnes in vitro. We evaluated the efficacy and safety of KTZ cream in mild adult female acne (AFA) by conducting a randomized, double‐blind, placebo‐controlled trial using KTZ 2% and placebo cream twice daily for 10 weeks. We assessed the improvement of clinical severity, measured by AFA score graded by investigators and participants, and the change of acne count. Forty‐one participants enrolled in our study. The proportion of participants with acne improvement from baseline (42.9% vs 9.5%, P = 0.015) and the success rate (45.0% vs 14.3%, P = 0.043) in the KTZ group were significantly higher than that of the placebo group. The most common adverse events were dryness and itching. The percentage change of acne count decreased significantly compared with baseline but did not differ statistically between the two groups (P = 0.268). We concluded that the KTZ monotherapy showed a plausible effect in improving AFA with excellent safety profile. It should be considered as a viable option for mild AFA treatment.

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“…The inhibitory actions of androgens on hair follicle cycling are undisputed, where 5α‐dihydrotestosterone (5α‐DHT) is more potent than the principal circulating androgen, testosterone, due to its greater affinity (2.5‐5 times) and stability for androgen receptors (Figure ). This example demonstrates the importance of how testosterone is converted by the steroidogenic enzymes, 5α‐reductase (type I‐III) along with their functional characteristics in hair follicles and ultimately the transmission of these chemical signals via androgen receptors . In this regard, it is crucial to keep in mind the features of each steroidogenic enzyme since testosterone also may be converted to estradiol via the aromatase enzyme .…”

Section: α‐Reductase 5α‐dihydrotestosterone (5α‐dht) and The Humanmentioning

confidence: 99%

Human scalp hair: Modulation by various factors and hormones do estrogens inhibit or stimulate—A perplexing perspective

Lephart

2019

J of Cosmetic Dermatology

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Summary Several journal reports, reviews, and commentaries over the last 20‐25 years have pointed out the controversy attached to 17β‐estradiol's inhibitory or stimulatory influence on hair follicle growth/cycling citing rodent (murine) and human results. While 17β‐estradiol is the most potent sex steroid hormone in the body and has almost equal affinity for estrogen receptor (ER) alpha (α) and beta (β), there appears to be specific ER‐mediated effects on scalp hair follicles/growth, etc. Additionally, the newly discovered G protein‐coupled estrogen receptor (GPR30 or GPER) and the orphan receptor, estrogen‐related receptor (ERR) gamma (γ), in skin and other tissue sites have potential impacts of how estrogens via these receptors may alter scalp hair characteristics, but this remains to be elucidated. Conversely, the negative impact of the 5α‐reductase enzyme and its steroid product, 5α‐dihydrotestosterone, on scalp hair growth is clear. Less clear is how 17β‐estradiol is stimulatory in some scalp hair studies, but inhibitory in others. This brief summary examines the potential influences of steroidogenesis via aromatase (estrogen biosynthesis) and 5α‐reductase expression, their enzyme activities, and steroid products along with the concepts of how steroid acute regulatory protein (StAR) and estrone sulfate may be involved in the complex hormonal, cellular/molecular signaling cascade of the hair follicle in growth and cycling.

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Androgens and androgen receptor action in skin and hair follicles

Cited by 143 publications

References 163 publications

Homeostasis of the sebaceous gland and mechanisms of acne pathogenesis

Homeostasis of the sebaceous gland and mechanisms of acne pathogenesis

Topical 2% ketoconazole cream monotherapy significantly improves adult female acne: A double‐blind, randomized placebo‐controlled trial

Human scalp hair: Modulation by various factors and hormones do estrogens inhibit or stimulate—A perplexing perspective

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