INTRODUCTION & HYPOTHESIS
Androgens are key regulators of sebaceous function. We previously showed that DHT clearly induced the lipogenic differentiation of androgen sensitive sebocytes cultured in defined medium without the addition of any factor or specific metabolic complementation1. In a functional DHT-induced lipid accumulation assay, we identified the mTOR inhibitors rapamycin and torin as potential active compounds (SID poster#3). A link between mTOR and androgen signaling has previously been reported e.g. in androgen-sensitive prostate cancer cells, as well as a link between these processes and lipid synthesis2. 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.
Androgen-induced lipogenic differentiation of androgen sensitive sebocytes is linked to mTOR pathway activation.
*Poster#3: Pharmacological effects of anti-androgens and other compounds in an androgen-sensitive sebocyte cell line.
MATERIALS & MEHODS
The mTOR antagonists rapamycin and torin were tested at 0.1 µM (SID poster#3*), alone or in association. Lipid accumulation was evidenced after 7 days by incubation with the fluorescent probe Bodipy®, and image analysis1. Lipid neosynthesis was measured after [14C]- acetate incorporation into lipids, chromatography and phosphorimaging1. Phospho-RPS6 and p62/SQSMT1 were evidenced by immunofluorescence after 6 h and 3/7 days, respectively. LC3II/I and p62/SQSMT1 relative expression were analysed by western blot after 3/7 days, as well as AKT phosphorylation (20 min activation by DHT or EGF).
RESULTS
1 – Effects of rapamycin, torin and their association (0.1 µM) on lipid synthesis/accumulation, after 7 days in control and DHT-treated sebocyte cells; immunofluorescence imaging & fluorescence quantification.
CONCLUSIONS
In this model,
– The mTOR inhibitors Rapamycin and Torin inhibit DHT-induced lipid neosynthesis and accumulation in SEBO662AR cells.
– Conversely, DHT stimulates mTOR activation, through an AKT-independent pathway. Such effects have been previously reported in other androgen-sensitive models.
– As an expected consequence, DHT slows down the autophagic process.
– These results highlight a link between androgen stimulation, mTOR activation, autophagy limitation and lipogenic effects, in these sebocyte cells.
REFERENCES
1 Barrault et al. (2015) J Steroid Biochem Mol Biol ;152:34-44
2 Audet-Walsh et al. (2018) Mol Cancer Res ; 16:1396-1405
Innate immunity activation of sebocyte cells by living bacteria. Evidence of a potential immunosuppressive effect of DHT.
Acné, Acné, Microbiome cutané, Microbiome cutané, Microbiome cutané, Sebaceous gland regulationAcne 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.
Pharmacological effects of anti-androgens and other compounds in an androgen-sensitive sebocyte cell line.
Acné, Acné, Sebaceous gland regulationWe 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.
Androgens activate lipogenesis through an AKT-independent mTOR pathway stimulation and a limitation of autophagy in an androgen-sensitive sebocyte cell line.
Acné, Acné, Peau grasse, hyperséborrhée et séborégulation, Sebaceous gland regulationAndrogens 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.
Acné vulgaris : Origines, symptômes et traitements actuels
AcnéL’acné vulgaris est une maladie inflammatoire chronique cutanée qui touche la plupart des adolescents et concerne plus de la moitié des consultations en dermatologie. Cette pathologie, caractérisée par une hypersécrétion de sébum peut être à l’origine de complications d’ordre physique pouvant également entraîner un certain mal-être psychologique.
Acné vulgaris : Physiopathologie et mécanismes cellulaires
Acné, Peau grasse, hyperséborrhée et séborégulationL’acné vulgaris est une pathologie inflammatoire chronique cutanée localisée au niveau du follicule pilo-sébacé. Elle apparaît suite à une surproduction de sébum liée à des dysfonctionnements d’origine hormonale (androgène), environnementale (pollution…) et à la colonisation du follicule pilo-sébacé par certaines bactéries (P. acnes).
(Dans ce contexte), QIMA Life Sciences a développé un panel de tests originaux destinés à la découverte et l’évaluation de composés pour le traitement de l’acné.
La glande sébacée : Physiologie et fonctions
Acné, Barrière cutanée et hydratation, Peau grasse, hyperséborrhée et séborégulationLa glande sébacée est un organe localisé au niveau du derme. Elle est responsable de la synthèse et de la sécrétion du sébum qui entre dans la composition du film hydrolipidique. Le rôle du sébum est de protéger la peau des agressions extérieures et de la déshydratation. Le sébum permet également d’entretenir la souplesse de la peau et des cheveux.