Endocrine Abstracts (2009) 20 P479

Short term elevation of estradiol concentrations does not affect hepatic VLDL-TG production

Lars C Gormsen, Christian Host, Claus Gravholt, Jens S Christiansen & Soren Nielsen

Aarhus University Hospital, Aarhus, Denmark.

Background: Hormone replacement therapy (HRT) in post-menopausal women carries an increased risk of cardiovascular disease due to an unfavorable effect on lipid profile. Thus, HRT treatment increases concentrations of very-low-density-lipoprotein-triglycerides (VLDL-TGs) which have been demonstrated to possess atherogenic properties. However, the exact mechanisms whereby VLDL-TG concentrations are increased by estradiol are not fully understood. Estradiol acts on both rapid responding intracellular receptors and on slow responding membrane bound receptors. We therefore aimed to study whether or not hepatic VLDL-TG production is acutely increased by a single dose of estradiol.

Materials and methods: In a single blinded cross-over design, eight postmenopausal women (age 57±5 years, BMI 25±2 kg/m2, fat mass 24±5 kg, lean body mass 40±4 kg) were investigated twice. Study days consisted of either placebo (CON) or 4 mg of estradiol (EST) administered p.o. 1 h before the study start. VLDL-TG kinetics were determined by a primed-constant infusion of (1-14C)triolein labeled VLDL and body composition by dual X-ray absorptiometry (DXA).

Results: By design, estradiol concentrations were below detection threshold during CON conditions and were significantly increased to ~0.5 nmol/l during EST conditions. No acute changes in VLDL-TG concentrations (VLDL-TG (mmol/l): CON: 0.39±0.15 versus EST: 0.41±0.23, P=0.78) or total TG concentrations (TG (mmol/l): CON: 1.25±0.57 versus EST: 1.11±0.39, P=0.38) were observed. Dynamic VLDL-TG kinetic parameters revealed that estradiol does not acutely impact on neither hepatic VLDL-TG production (VLDL-TG production (μmol/min) CON: 20±12 versus EST: 23±9, P=0.52) nor peripheral VLDL-TG clearance (VLDL-TG clearance (ml/min): CON: 49±15 versus EST: 64±29, P=0.28).

Conclusion: Acute administration of estradiol does neither affect hepatic VLDL-TG production nor peripheral VLDL-TG clearance. The mechanisms behind estradiol’s effects upon circulating lipids remain to be elucidated.

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