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1.Bioalternatives, Gençay, France

Samuel Guenin1, Julien Garnier1, Christine Barrault1, Nathalie Pedretti1, Sevda Cordier-Dirikoc1, François-Xavier Bernard1

intracellular metabolites in an androgen-sensitive sebocyte cell line.

Behavior of the two circulating androgens testosterone and DHEA and their main

INTRODUCTION & HYPOTHESIS

Androgens are known to strongly regulate the physio-pathological status of the sebaceous gland. Acne, oily and dry skin are induced or modulated by active androgens, and relationships with the circulating testosterone (TESTO) level have been currently reported. On another hand, little is known about a potential role of the second major circulating androgen dehydroepiandrosterone DHEA in these processes, and speculations about the role of DHEA by itself or in regulating the effects of other androgens have never been clearly confirmed.
We previously established a sebocyte cell line constitutively expressing a functional androgen receptor (AR)1. We showed that the most potent intracellular androgen metabolite, dihydrotestosterone (DHT), induced AR translocation, specific transcripts such as ras-related dexamethasone induced 1 (RASD1) and lipogenesis/lipid storage. We used these parameters to assess the behaviour and activity of the two main circulating androgens TESTO and DHEA, in comparison with DHT, in this model.

The SEBO662AR cell line metabolizes testosterone (which is an active androgen by itself), into other active androgens, especially DHT. The androgenic effect of DHEA by itself or after its potential metabolism remains hypothetic, as well as its influence on the effects of other androgens especially testosterone. We analysed the effects of TESTO and DHEA and their metabolites in this androgen-responsive model.

MATERIALS & MEHODS

AR translocation was followed by immunofluorescence1. Lipid accumulation was evidenced by incubation with the fluorescent probe Bodipy®1. RASD1 expression was measured by RT-qPCR1.
Relative expression levels of the androgen-metabolizing enzyme transcripts were obained from Affymetrix full transcriptome data1. [14C]-TESTO and [14C]-DHEA metabolism was analysed after incubation with cell cultures for different times followed by metabolite extraction, chromatography/phosphorimaging as previously described2.

RESULTS

1 – Exogenous androgens (TESTO, DHEA) & DHT activity
2 – Exogenous androgens (TESTO, DHEA) metabolism & activity
Download the full version of the poster to see all the results

CONCLUSIONS

In this model,

– TESTO is an active androgen by itself and is converted into DHT through the activity of type 1 5-alpha reductase. DHT direct androgenic activity is achieved at concentrations 10-fold lower than TESTO. Other metabolites are also formed such as –dione metabolites which exhibit a low but significant androgenic activity (> 10-fold less active than TESTO).

– DHEA is totally inactive by itself. It is not transformed into TESTO and 3bHSD expression was not detected. DHEA is very slowly metabolized into androsterone and other discrete species. Androsterone is moderately active by itself (> 10-fold less active than TESTO) and could explain the low activity of DHEA in long term assays.

– An excess of DHEA did not interfere with Testo metabolism and DHT production, nor with the androgenic activity of DHT, thus it cannot be considered as a “competitor” of TESTO.

REFERENCES

1 Barrault et al. (2015) J Steroid Biochem Mol Biol ;152:34-44
2 Bernard et al. (2000) Int J Cosmet Sci ;22:397-407

Innate immunity activation of sebocyte cells by living bacteria. Evidence of a potential immunosuppressive effect of DHT.

22 May 2019/in Acne, Microbiome cutané, Sebaceous gland regulation, Skin microbiome, Skin microbiome /by Vanessa

Acne is a skin pathology targeting the pilosebaceous unit…sebum hypersecretion and bacterial infection. We studied the effects of living bacteria on the induction of an innate immune response in a sebocyte cell line.

Read more
https://www.bioalternatives.com/wp-content/uploads/2019/05/190527_Poster1_petit.png 368 655 Vanessa https://www.bioalternatives.com/wp-content/uploads/2019/09/Logo-Bioalternatives-150dpisite-web2-300x74.png Vanessa2019-05-22 14:37:542019-11-12 17:58:17Innate immunity activation of sebocyte cells by living bacteria. Evidence of a potential immunosuppressive effect of DHT.

Pharmacological effects of anti-androgens and other compounds in an androgen-sensitive sebocyte cell line.

22 May 2019/in Acne, Sebaceous gland regulation /by Vanessa

We analysed the activity of reference anti-androgens (Finasteride, Dutasteride, Cyproterone acetate), at the level of their potential targets (5-alpha-reductase, AR translocation, induced transcripts) and in a functional lipid accumulation assay. We also evaluated this androgen-induced lipid accumulation assay as a potential pharmacological tool to detect potential inhibitors from both androgenic and non-androgenic origins.

Read more
https://www.bioalternatives.com/wp-content/uploads/2019/05/190527_Poster3_petit.png 368 655 Vanessa https://www.bioalternatives.com/wp-content/uploads/2019/09/Logo-Bioalternatives-150dpisite-web2-300x74.png Vanessa2019-05-22 14:37:122019-11-12 17:36:48Pharmacological effects of anti-androgens and other compounds in an androgen-sensitive sebocyte cell line.

Androgens activate lipogenesis through an AKT-independent mTOR pathway stimulation and a limitation of autophagy in an androgen-sensitive sebocyte cell line.

22 May 2019/in Acne, Peau grasse, hyperséborrhée et séborégulation, Sebaceous gland regulation /by Vanessa

Androgens are key regulators of sebaceous function… A link between mTOR and androgen signaling has previously been reported…as well as a link between these processes and lipid synthesis…Here we aimed at confirming that DHT-induced lipid synthesis/accumulation is at least in part dependent on mTOR activation in the SEBO662AR cell line and that the autophagic process is consequently modified by the androgenic treatment.

Read more
https://www.bioalternatives.com/wp-content/uploads/2019/05/190527_Poster4_petit.png 368 655 Vanessa https://www.bioalternatives.com/wp-content/uploads/2019/09/Logo-Bioalternatives-150dpisite-web2-300x74.png Vanessa2019-05-22 14:37:042019-11-12 17:39:16Androgens activate lipogenesis through an AKT-independent mTOR pathway stimulation and a limitation of autophagy in an androgen-sensitive sebocyte cell line.
Various forms of acne vulgaris

Acne vulgaris: Origins, symptoms and current treatments

29 November 2017/in Acne /by Julie

Acne vulgaris is a chronic inflammatory disease of the skin which affects most adolescents and is the cause of over half of all dermatology consultations. This pathology, which is characterized by a hypersecretion of sebum, can be the cause of physical complications and may also lead to psychological distress.

Read more
https://www.bioalternatives.com/wp-content/uploads/2017/11/Acné-généralité-image-à-la-une-_-EN.jpg 368 655 Julie https://www.bioalternatives.com/wp-content/uploads/2019/09/Logo-Bioalternatives-150dpisite-web2-300x74.png Julie2017-11-29 09:31:592019-11-12 14:28:03Acne vulgaris: Origins, symptoms and current treatments

Acne vulgaris: physiopathology and cell mechanisms

29 November 2017/in Acne, Sebaceous gland regulation /by Julie

Acne Vulgaris is a chronic inflammatory pathology located in the region of the pilosebaceous follicle. It occurs following a high production of sebum linked to hormonal (androgynous) or environmental (pollution) malfunctioning and to the colonization of the pilosebaceous follicle by certain bacteria (P. acnes).
Bioalternatives has developed a panel of innovative assays to discover and evaluate compounds for the treatment of acne.

Read more
https://www.bioalternatives.com/wp-content/uploads/2017/11/Image-à-la-une.jpg 368 655 Julie https://www.bioalternatives.com/wp-content/uploads/2019/09/Logo-Bioalternatives-150dpisite-web2-300x74.png Julie2017-11-29 09:30:252019-09-13 07:40:20Acne vulgaris: physiopathology and cell mechanisms

Physiology and functions of the sebaceous gland

28 November 2017/in Acne, Sebaceous gland regulation, Skin barrier and hydration /by Julie

The sebaceous gland is an organ located in the dermis. Its role is to synthesise and secrete sebum which is a component of the hydrolipidic film. The purpose of sebum is to protect the skin from external aggression and dehydration. Sebum also maintains the suppleness of the skin and hair.

Read more
https://www.bioalternatives.com/wp-content/uploads/2017/11/Sébocytes-image-à-la-une.jpg 368 701 Julie https://www.bioalternatives.com/wp-content/uploads/2019/09/Logo-Bioalternatives-150dpisite-web2-300x74.png Julie2017-11-28 09:24:342019-11-07 15:45:07Physiology and functions of the sebaceous gland

Androgens induce sebaceous differentiation in sebocyte cells expressing a stable functional androgen receptor

9 April 2015/in Acne, Cell and tissue engineering, Sebaceous gland regulation /by Guillaume

In order to study the impact of active androgens in sebocytes, we constructed a stable human sebocyte cell line derived from SEBO662 [17] constitutively expressing a fully functional AR. In these SEBO662 AR+ cells, dihydrotestosterone (DHT) induced AR nuclear translocation and the strong modulation of a set of transcripts (RASD1, GREB1…) known to be androgen-sensitive in other androgenic cells and tissues.

Read more
https://www.bioalternatives.com/wp-content/uploads/2016/03/mw_androgens-induce-sebaceous-differentiation-in-sebocyte.jpg 368 655 Guillaume https://www.bioalternatives.com/wp-content/uploads/2019/09/Logo-Bioalternatives-150dpisite-web2-300x74.png Guillaume2015-04-09 15:47:492019-11-13 11:16:58Androgens induce sebaceous differentiation in sebocyte cells expressing a stable functional androgen receptor

Immortalized sebocytes SEBO662 can spontaneously differentiate into a sebaceous-like phenotype when cultured as a 3D epithelium

24 January 2012/in Acne, Cell and tissue engineering, Sebaceous gland regulation /by Guillaume

SEBO662 multilayers spontaneously differentiate into a sebaceous-like structure as shown by the strong polarized expression of the late sebaceous marker EMA, the overexpression of some lipogenic markers and lipid production on the upper side of the epithelium.

Read more
https://www.bioalternatives.com/wp-content/uploads/2016/05/mw_Immortalized-sebocytes.jpg 368 655 Guillaume https://www.bioalternatives.com/wp-content/uploads/2019/09/Logo-Bioalternatives-150dpisite-web2-300x74.png Guillaume2012-01-24 10:17:152019-11-13 11:28:55Immortalized sebocytes SEBO662 can spontaneously differentiate into a sebaceous-like phenotype when cultured as a 3D epithelium
skin inflammation

Keratinocytes as targets for cytokines in skin inflammation

20 November 2008/in Acne, Atopic dermatitis, Dermatology, Psoriasis /by Guillaume

Current knowledge about the effects of different cytokine families on keratinocytes, and more particularly theirinvolvement in skin inflammation and in the development of inflammatory skin diseases such as psoriasis

Read more
https://www.bioalternatives.com/wp-content/uploads/2016/05/mw_Keratinocytes-as-targets-for-cytokines.jpg 368 655 Guillaume https://www.bioalternatives.com/wp-content/uploads/2019/09/Logo-Bioalternatives-150dpisite-web2-300x74.png Guillaume2008-11-20 14:50:532019-05-31 09:36:35Keratinocytes as targets for cytokines in skin inflammation
5-alpha-reductase

Expression of type 1 5-alpha-reductase and metabolism of testosterone in reconstructed human epidermis

10 December 2000/in Acne, Dermatology /by Guillaume

We analysed the potential of a human epidermal tissue reconstituted by cell culture (RHE, provided by SkinEthic Laboratories, Nice, France) as a model for assessing 5-alphaR activity.

Read more
https://www.bioalternatives.com/wp-content/uploads/2016/05/mw_Expression-of-type-5alpha-reductase.jpg 368 655 Guillaume https://www.bioalternatives.com/wp-content/uploads/2019/09/Logo-Bioalternatives-150dpisite-web2-300x74.png Guillaume2000-12-10 13:36:372018-10-24 22:15:34Expression of type 1 5-alpha-reductase and metabolism of testosterone in reconstructed human epidermis

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Bioalternatives, Inc.
250 Park Avenue, 7th Floor,
New York, NY, 10177, USA
Tel. +1 (212) 364 5115
Mail: info.us[@]bioalternatives.com

Bioalternatives SASU
1bis rue des plantes - CS 50011
86160 Gençay - France
Tel. +33 (0) 5 49 36 11 37
Mail: info[@]bioalternatives.com

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Cosmetic

  • Hydration and skin barrier
  • Epidermal regeneration
  • Skin firmness & cohesion
  • Skin ageing
  • Skin protection & defense
  • Skin pigmentation
  • Oily skin and hyperseborrhea
  • Skin microcirculation and vascularization
  • Slimming and adipocyte metabolism
  • Hair growth and alopecia

Pharmacology

  • Immuno-Inflammation
  • Neurobiology
  • Veterinary medicine

Dermatology

  • Acne
  • Hair growth and alopecia
  • Atopic dermatitis
  • Psoriasis
  • Wound healing and skin regeneration
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  • Vitiligo (coming soon)
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