Androgen regulation of lipogenic pathways in the mouse meibomian gland.
We hypothesize that androgens regulate lipogenesis in the meibomian gland. To test this hypothesis, we sought to determine whether androgens increase the mRNA levels of key lipogenic enzymes involved in the synthesis of cholesterol and fatty acids. In addition, we examined whether androgens stimulate the expression of genes for sterol regulatory element binding proteins (SREBP) 1 and 2, which are transcription factors that play an important role in the coordinate regulation of lipogenic enzymes. Meibomian glands were obtained from castrated mice, that were treated with vehicle or testosterone for 2 weeks. Tissues were processed for the analysis of selected mRNAs by real-time PCR. Our results show that testosterone increases the mRNA levels of critical lipogenic enzymes, including those related to ATP-citrate lyase, acetyl-CoA-synthase, acetyl-CoA-carboxylase, acetoacetyl-CoA-synthase and 3-hydroxy-3-methylglutaryl CoA synthase 1. Our findings also demonstrate that androgens upregulate the expression of genes encoding the transcription factors SREBPs 1 and 2. Our results indicate that androgens may control multiple aspects of lipogenesis in the meibomian gland.
Schepens Eye Research Institute and the Department of Ophthalmology, Harvard Medical School, 20 Staniford Street, Boston, MA 02114, USA.
Frank
F
Schirra
Stephen M
SM
Richards
Meng
M
Liu
Tomo
T
Suzuki
H
H
Yamagami
David A
DA
Sullivan
D000728:Androgens / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002784:Cholesterol / Q000096:biosynthesis; D005227:Fatty Acids / Q000096:biosynthesis; D005786:Gene Expression Regulation / Q000235:genetics; D050155:Lipogenesis / Q000502:physiology*; D008297:Male; D008537:Meibomian Glands / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000032:analysis; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics; D051782:Sterol Regulatory Element Binding Protein 2 / Q000235:genetics; D013739:Testosterone / Q000494:pharmacology; D015854:Up-Regulation / Q000235:genetics
D000728:Androgens; D005227:Fatty Acids; D012333:RNA, Messenger; C497388:Srebf1 protein, mouse; C497391:Srebf2 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D051782:Sterol Regulatory Element Binding Protein 2; D013739:Testosterone; D002784:Cholesterol