Involvement of the SREBP pathway in the mode of action of androgens in sebaceous glands in vivo.
Androgens have profound effects on the physiology of the sebaceous gland. Using the hamster ear sebaceous gland model, we performed a detailed kinetic study to clarify the mechanism of androgen action on sebaceous gland function. We demonstrated that the growth of sebaceous glands observed after androgen treatment was due to both an increase in sebocyte proliferation and a parallel induction of sebocyte terminal differentiation, as evidenced by the induction of the synthesis of specific sebaceous lipids such as cholesterol esters, triglycerides, and squalene. Accordingly, the effect of androgen treatment on the mRNA expression of several key enzymes involved in the synthesis of sebaceous lipids has been studied using semi-quantitative RT-PCR. Up-regulation by androgens of mRNA expression of HMG coenzyme A synthase and reductase, acetyl coenzyme A carboxylase (ACC), glycerol 3-phosphate acyl transferase (GPAT), and FAR-17c (stearoyl coenzyme A desaturase homologous), was demonstrated. Because sterol-response element(s) (SREs) are known to be present in the promoters of these genes, we analyzed the expression by RT-PCR and the activation of the transcription factor sterol regulatory element binding protein (SREBP) using immunoblotting experiments. Our results showed that SREBP-1 was up-regulated and rapidly activated after androgen treatment. Altogether, these results demonstrate for the first time that in sebaceous glands, in vivo, androgen regulates the synthesis of sebum lipids through the SREBP pathway.
Rosignoli
C
C
GALDERMA R & D, Sophia Antipolis cedex, Valbonne, France; INSERM U439 Pathologie Moléculaire des Récepteurs Nucléaires, Montpellier, France.
Nicolas
J C
JC
Jomard
A
A
Michel
S
S
D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D006224:Cricetinae; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D013196:Dihydrotestosterone / Q000494:pharmacology; D004798:Enzymes / Q000235:genetics; D005260:Female; D006888:Hydroxycholesterols / Q000494:pharmacology; D050356:Lipid Metabolism; D008647:Mesocricetus; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012627:Sebaceous Glands / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; D015854:Up-Regulation / Q000187:drug effects
D000728:Androgens; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D004798:Enzymes; D006888:Hydroxycholesterols; D012333:RNA, Messenger; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; D013196:Dihydrotestosterone; C007997:25-hydroxycholesterol