Effects of dihydrotestosterone on adipose tissue measured by serial analysis of gene expression

Abstract

Intra-abdominal fat accumulation is related to several diseases, especially diabetes and heart disease. Molecular mechanisms associated with this independent risk factor are not well established. Through the serial analysis of gene expression (SAGE) strategy, we have studied the transcriptomic effects of castration and dihydrotestosterone (DHT) in retroperitoneal adipose tissue of C57BL6 male mice. Approximately 50 000 SAGE tags were isolated in intact and gonadectomized mice, as well as 3 and 24 h after DHT administration. Transcripts involved in energy metabolism, such as glyceraldehyde-3-phosphate dehydrogenase, malic enzyme supernatant, fatty acid synthase, lipoprotein lipase, hormone-sensitive lipase and monoglyceride lipase, were upregulated by DHT. Transcripts involved in adipogenesis, and cell cycle and cell shape organization, such as DDX5, C/EBP , cyclin I, procollagen types I, III, IV, V and VI, SPARC and matrix metalloproteinase 2, were upregulated by DHT. Cell defense, division and signaling, protein expression and many novel transcripts were regulated by castration and DHT. The present results provide global genomic evidence for a stimulation of glycolysis, fatty acids and triacylglycerol production, lipolysis and cell shape reorganization, as well as cell proliferation and differentiation, by DHT. The novel transcripts regulated by DHT may contribute to identify new mechanisms involved in the action of sex hormones and their potential role in obesity.

Hypoxia-Inducible Factor-3.ALPHA. Functions as an Accelerator of 3T3-L1 Adipose Differentiation

“…Several studies suggested that DEAD box polypeptide 5 (Ddx5) (also referred to as p68 RNA helicase) is involved in organ/tissue differentiation, 39) and it was recently reported that expression of the Ddx5 gene in murine adipose tissues was increased by the administration of dihydrotestosterne. 40) SWI/SNF-related matrix-associated actindependent regulator of chromatin subfamily b member 1 (Smarcb1) belongs to SWI/SNF family, which posseses helicase and ATPase activities and is thought to regulate the transcription of certain genes by altering the chromatin structure around those genes. 41) It was also reported that expression of Smarcb1 was increased in human adipocytes compared with that in preadipocytes.…”

Androgens influence expression of matrix proteins and proteolytic factors during cutaneous wound healing

“…46 Wound MMP-2 and MMP-9 activities on day 6 post-injury were reduced in castrated animals, suggesting that, following wounding, androgens stimulate local gelatinase activity. While few published data pertain to the regulation by androgens of MMP-9, the expression of MMP-2 was reported to be DHT-and (synthetic androgen) R1881-induced in adipose tissue 47 and LNCaP cells, respectively. 48 Moreover, this latter response is effected by binding of the activated androgen receptor to a pair of androgen-response elements within the MMP-2 promoter.…”

Response of the adipose tissue transcriptome to dihydrotestosterone in mice

“…The impact of androgens on gene transcription in adipose tissue from male mice has been previously examined by serial analysis of gene expression in one study (7). Although very informative, that approach did not consider temporal expression regulation in response to the hormone.…”