Estradiol acutely inhibits whole body lipid oxidation and attenuates lipolysis in subcutaneous adipose tissue: a randomized, placebo-controlled study in postmenopausal women.

CONTEXT: Estradiol (E(2)) promotes and maintains the female phenotype characterized by subcutaneous fat accumulation. There is evidence to suggest that this effect is due to increased anti-lipolytic α2A-adrenergic receptors, but whether this requires long-term exposure to E(2) or is an immediate effect is not clear. OBJECTIVE: To study acute effects of a single dose (4 mg) of 17ß-E(2) on regional and systemic lipolysis. METHODS: Sixteen postmenopausal women (age, 595 years; weight, 6710 kg; and BMI, 24.82.9) were studied in a crossover design: i) placebo and ii) 4 mg E(2). Basal and adrenaline-stimulated regional lipolysis was assessed by microdialysis and substrate oxidation rates by indirect calorimetry. Tissue biopsies were obtained to assess lipoprotein lipase activity and mRNA expression of adrenergic, estrogen, cytokine, and vascular reactivity receptors. RESULTS: Acute E(2) stimulation significantly attenuated catecholamine-stimulated lipolysis in femoral subcutaneous adipose tissue (interstitial glycerol concentration (micromole/liter) ANOVA time vs treatment interaction, P=0.01) and lipolysis in general in abdominal adipose tissue (ANOVA treatment alone, P<0.05). E(2) also reduced basal lipid oxidation ((mg/kg per min) placebo, 0.58 ± 0.06 vs E(2), 0.45 ± 0.03; P=0.03) and induced a significantly higher expression of anti-lipolytic α2A-adrenergic receptor mRNA (P=0.02) in skeletal muscle tissue as well as an upregulation of eNOS (NOS3) mRNA (P=0.02). CONCLUSION: E(2) acutely attenuates the lipolytic response to catecholamines in subcutaneous adipose tissue, shifts muscular adrenergic receptor mRNA toward anti-lipolytic α2A-receptors, decreases whole body lipid oxidation, and enhances expression of markers of vascular reactivity.

Acute estrogen exposure does not affect basal very low-density lipoprotein-triglyceride production or oxidation in postmenopausal women.

CONTEXT: Long-term hormone replacement therapy (HRT) with estradiol (E(2)) is associated with an altered lipid profile including unfavorable increases in triglyceride (TG) concentrations and augmented hepatic very low-density lipoprotein (VLDL)-TG production. There are indications that this effect of estrogens may be immediate. OBJECTIVE: To study the in vivo effect of a single dose of E(2) on VLDL-TG kinetics and oxidation in humans. METHODS: Eight healthy, postmenopausal women were given a single dose of either placebo or E(2) (4 mg) orally. VLDL-TG kinetics was assessed by a 240-min primed-continuous infusion of ex vivo labeled [1-(14)C]triolein-labeled VLDL. Fractional and absolute VLDL-TG oxidation was determined by hyamin trapping of exhaled (14)C label. Indirect calorimetry provided measurements of lipid oxidation. RESULTS: Administration of 4 mg of E(2) orally rapidly increased plasma E(2) concentrations from below detection threshold to premenopausal levels. Free fatty acids (FFA) and TG concentrations were unaltered. No immediate effect was observed on either VLDL-TG production (placebo versus E(2)): 20.0+/-12.4 vs 24.1+/-10.7 micromol/min, P=0.33; VLDL-TG oxidation: 12.3+/-10.9 vs 12.6+/-5.6 micromol/min, P=0.93); or VLDL-TG clearance rates: 51.4+/-16.8 vs 64.9+/-28.8 ml/min, P=0.34). CONCLUSIONS: Short-term E(2) elevation does not affect VLDL-TG production, oxidation, or clearance in humans. We therefore propose that HRT-associated dyslipidemia has a gradual rather than immediate onset.

Clinical and epidemiological description of aortic dissection in Turner's syndrome.

BACKGROUND: Women with Turner's syndrome have an increased risk of congenital cardiac malformations, ischaemic heart disease, hypertension and stroke. Aortic dissection seems to occur with increased frequency. AIM: To describe in more detail aortic dissection as encountered in Turner's syndrome, giving attention to clinical, histological and epidemiological aspects. MATERIALS AND METHODS: Based on a retrospective study, we describe the clinical, karyotypic, and epidemiological aspects of aortic dissection as encountered in cases of Turner's syndrome seen in Denmark and Sweden. RESULTS: The median age at onset of aortic dissection in 18 women was 35 years, ranging from 18 to 61 years. Fourteen of 18 women had a 45,X karyotype, while 2 patients had 45,X/45,XY, and 2 had the 45,X/46,X+r(X) complement, respectively. Echocardiography was performed in 10 of 18 patients before their acute illness, and showed signs of congenital cardiac disease, with either bifoliate aortic valves, dilation of the aortic root, or previous aortic coarctation evident in most patients. In 5 patients evidence of a bifoliate aortic valve was conclusive. Hypertension was present in 5 of 18 patients, while 10 of the patients died from aortic dissection, of so-called type A in 6, type B in 3, while in the final case the origin of dissection could not be determined. Biochemical analysis showed altered ratio between type I and type III collagen. Histology showed cystic medial necrosis in 3 of 7 cases. We estimated an incidence of dissection of 36 per 100,000 Turner's syndrome years, compared with an incidence of 6 per 100,000 in the general population, and a cumulated rate of incidence of 14, 73, 78, and 50 per 100,000 among 0-19, 20-29, 30-39, and 40+ year olds, respectively. CONCLUSION: Aortic dissection is extremely common in the setting of Turner's syndrome, and occurs early in life. Patients with Turner's syndrome should be offered a protocol for clinical follow-up similar to that provided for patients with Marfan syndrome, and each clinic should embrace a programme for follow-up.

Effect of growth hormone and 17beta-oestradiol treatment on metabolism and body composition in girls with Turner syndrome.

OBJECTIVE: Girls with Turner syndrome (TS) receive GH treatment during childhood, and in adolescence this treatment may be combined with oestradiol. We have studied the effects of this combined treatment on metabolism and body composition. MATERIAL AND METHODS: We performed a double-blind, placebo-controlled, randomized, crossover study. All girls with TS (n = 8, 16 +/- 2 years) were treated with placebo + placebo, GH + placebo or GH + 17beta-oestradiol for 2 months, and were studied at the end of each period. Controls (n = 10, 14 +/- 2 years) were studied once without treatment. Twenty-four-hour sampling of oestradiol, growth factors, insulin, glucose, lipolytic and gluconeogenic precursors was performed, followed by an oral glucose tolerance test (OGTT) and assessment of body composition and mineral content. RESULTS: GH induced insulin resistance, which was not aggravated further by concomitant oestradiol treatment. The 24-h integrated serum 17beta-oestradiol was reduced compared to controls (0.58 +/- 0.32 vs. 2.81 +/- 2.78 nmol/l/24 h, P = 0.032), but increased during GH + oestrogen (E2) treatment without reaching control levels, while GH + placebo caused a further reduction (anova, P = 0.008). Total fat mass was increased in girls with TS compared with controls (P = 0.009), while lean body mass (P = 0.02) and bone mineral content (P = 0.04) was decreased, with specific regional characteristics in body composition. CONCLUSION: GH treatment induces insulin resistance and changes in body composition in TS, which is not further compromised by concomitant oestradiol treatment. Body composition is changed in TS, with specific regional changes, in comparison with controls. Integrated 24-h oestradiol is low in TS, and is only partially restored during treatment with standard doses of 17beta-oestradiol.