Session: SUN 203-235-Steroid Hormone Actions, Biosynthesis and Metabolism (posters)
Bench to Bedside
Poster Board SUN 228
Objectives: We studied the activity of STS in the hydrolysis of E1S to E1 in AT in postmenopausal women, and determined STS and aromatase-encoding CYP19A1 gene mRNA expression levels. We also measured concentrations of E1 in serum and AT.
Subjects and methods: Subcutaneous and visceral AT samples were obtained from postmenopausal women undergoing surgery for non-malignant gynecological reasons at the Helsinki University Hospital (n=30, age 46-80 years, no hormone replacement therapy). We incubated whole AT homogenates with [3H]-E1S, and separated reaction products by hydrophobic column chromatography. [3H]-E1 liberated was determined by liquid-scintillation counting. STS and CYP19A1 mRNA expression levels were quantified by real-time qPCR. Liquid chromatography-tandem mass spectrometry was used to measure E1 concentrations in serum and AT.
Results: We found similar STS activity in subcutaneous (n=24) and visceral (n=21) AT, 4.7 (4.0-6.4) vs. 5.1 (4.2-6.1) nmol/kg adipose tissue/h (median, range). The relative mRNA expression levels of STS and CYP19A1 were higher in subcutaneous (n=16) than in visceral (n=17) AT, 0.30 (0.29-0,47) vs. 0.16 (0.11-0.40), P=0.001 for STS, and 0.23 (0.11-0.49) vs. 0.08 (0.03-0.44), P=0.008 for CYP19A1. E1 concentration was higher in visceral (960 pmol/kg) than in subcutaneous AT (734 pmol/kg, P=0.02) and serum (88 pmol/l, P<0.001). Serum concentration of E1 correlated with both subcutaneous (r=0.67, P<0.001, n=24) and visceral (r=0.69, P<0.001, n=29) AT E1 concentrations. STS mRNA expression correlated positively with E1 concentration in visceral AT (r=0.53, P=0.03, n=17), which in turn correlated with body mass index (BMI) (r=0.40, P=0.03, n=29). Visceral AT STS mRNA expression also correlated positively with serum E1 (r=0.59, P=0.01, n=17).
Conclusions: We show that STS is active in converting E1S to E1 in AT of postmenopausal women. mRNA expression levels of genes coding for key E1-producing enzymes, STS and CYP19A1, were higher in subcutaneous than in visceral AT, but E1 concentration was higher in visceral AT and showed a positive correlation with BMI and also serum E1. This suggests an important role of visceral AT in peripheral estrogen synthesis and metabolism in postmenopausal women.
Nothing to Disclose: NB, HS, EH, UT, FW, MJT, VV, TSM
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