The major glucocorticoids (cortisol in man and corticosterone in the rat) play an important role in obesity and its attendant hypertension. However, there is no consistent evidence of glucocorticoid excess in simple obesity, suggesting that its role in the regulation of adipose tissue mass results from a more complex mechanism than adrenal hypersecretion of glucocorticoid. Glucocorticoid biosynthesis is not limited to the adrenal cortex; mRNA and enzymatic activity of 11β-hydroxylase, the enzyme responsible for the terminal stage of corticosterone production, have been demonstrated in the rat brain. In this study we sought evidence for 11β-hydroxylase gene transcription in adipose tissue. We used a fully quantitative RT-PCR system utilising homologous RNA standards to detect 11β-hydroxylase mRNA in adipose tissue taken from the Zucker rat model of obesity.
We analysed omental and subcutaneous adipose tissue from the Zucker obese rat and its lean control (n=5 for each group). 11β-Hydroxylase transcripts were easily and reproducibly detected in omental tissue (4.7×105±9.4×104 mRNA copies/μg total RNA) at levels approximately 300-fold lower than the adrenal; adipose mRNA levels did not differ significantly between lean and obese animals. No transcripts could be detected in subcutaneous adipose RNA. Further experiments showed all adipose RNA samples to contain transcripts for the Steroidogenic Acute Regulatory (StAR) protein and the side-chain cleavage enzyme (P450scc) which are vital to de novo synthesis of glucocorticoid from cholesterol.
The local activation of glucocorticoid by the type 1 11β-hydroxysteroid dehydrogenase enzyme (11β-HSD1) in omental adipose tissue has attracted a great deal of interest and may play a role in the development of obesity by regulating adipocyte differentiation. Here we demonstrate omentum-specific 11β-hydroxylase expression for the first time, thus providing an additional mechanism for the local generation of glucocorticoid in adipose tissue.
01 - 05 Apr 2006
European Society of Endocrinology