Tamoxifen reduces hepatic VLDL production and GH secretion in women: a possible mechanism for steatosis development

European Journal of Endocrinology
Vita BirznieceKen K Y Ho

Abstract

Growth hormone (GH) stimulates hepatic synthesis of very-low-density lipoproteins (VLDL), whereas hepatic steatosis develops as a result of GH deficiency. Steatosis is also a complication of tamoxifen treatment, the cause of which is not known. As tamoxifen inhibits the secretion and action of GH, we hypothesize that it induces steatosis by inhibiting hepatic VLDL export. To investigate whether tamoxifen reduces hepatic VLDL secretion. Eight healthy, normolipidemic women (age: 64.4 ± 2.1 years) were studied in random sequence at baseline, after 2 weeks of tamoxifen (20 mg/day) and after 2 weeks of estradiol valerate (EV; 2 mg/day) treatments, separated by a 4-week washout period. The kinetics of apolipoprotein B (apoB), the structural protein of VLDL particles, were measured using a stable isotope 2H3-leucine turnover technique. VLDL-apoB fractional catabolic rate (FCR) was determined using a multicompartment model. VLDL-apoB secretion was estimated as the product of FCR and VLDL-apoB concentration. GH response to arginine stimulation, circulating levels of IGF-1, FFA, and TG, along with TG content in VLDL were measured. Tamoxifen significantly (P < 0.05) reduced VLDL-apoB concentration and secretion by 27.3 ± 7.8% and 29.8 ± 1...Continue Reading

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Citations

Jan 27, 2018·Current Opinion in Endocrinology, Diabetes, and Obesity·Vita Birzniece
Mar 29, 2019·The Journal of Clinical Endocrinology and Metabolism·Vita BirznieceKen K Y Ho
May 10, 2018·Frontiers in Pharmacology·David GrünigStephan Krähenbühl
Jul 2, 2019·Journal of the Endocrine Society·Yee-Ming CheungMathis Grossmann
Jun 30, 2019·Irish Veterinary Journal·Gonzalo GajardoClaudio Henríquez
Mar 23, 2021·Clinical Journal of Gastroenterology·Naoki TanakaAkira Horiuchi
Jul 28, 2021·Fundamental & Clinical Pharmacology·Enas A Abd El-Haleim, Nada A Sallam
Aug 15, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Maria Lucia Souza SiqueiraMarta Chagas Monteiro

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