Testosterone increases the muscle protein synthesis rate but does not affect very-low-density lipoprotein metabolism in obese premenopausal women

Abstract

Wang X, Smith GI, Patterson BW, Reeds DN, Kampelman J, Magkos F, Mittendorfer B. Testosterone increases the muscle protein synthesis rate but does not affect very-low-density lipoprotein metabolism in obese premenopausal women. Am J Physiol Endocrinol Metab 302: E740 -E746, 2012. First published January 17, 2012; doi:10.1152/ajpendo.00533.2011.-Men and women with hyperandrogenemia have a more proatherogenic plasma lipid profile [e.g., greater triglyceride (TG) and total and low-density lipoprotein-cholesterol and lower high-density lipoprotein-cholesterol concentrations] than healthy premenopausal women. Furthermore, castration of male rats markedly reduces testosterone availability below normal and decreases plasma TG concentration, and testosterone replacement reverses this effect. Testosterone is, therefore, thought to be an important regulator of plasma lipid homeostasis. However, little is known about the effect of testosterone on plasma TG concentration and kinetics. Furthermore, testosterone is a potent skeletal muscle protein anabolic agent in men, but its effect on muscle protein turnover in women is unknown. We measured plasma lipid concentrations, hepatic very low density lipoprotein (VLDL)-TG and VLDLapolipoprotein B-100 secretion rates, and the muscle protein fractional synthesis rate in 10 obese women before and after trandermal testosterone (1.25 g of 1% AndroGel daily) treatment for 3 wk. Serum total and free testosterone concentrations increased (P Ͻ 0.05) by approximately sevenfold in response to testosterone treatment, reaching concentrations that are comparable to those in women with hyperandrogenemia, but lower than the normal range for eugonadal men. Except for a small (ϳ10%) decrease in plasma high-density lipoprotein particle and cholesterol concentrations (P Ͻ 0.04), testosterone therapy had no effect on plasma lipid concentrations, lipoprotein particle sizes, and hepatic VLDL-TG and VLDL-apolipoprotein B-100 secretion rates (all P Ͼ 0.05); the muscle protein fractional synthesis rate, however, increased by ϳ45% (P Ͻ 0.001). We conclude that testosterone is a potent skeletal muscle protein anabolic agent, but not an important regulator of plasma lipid homeostasis in obese women. triglyceride; apolipoprotein B; muscle protein synthesis MEN HAVE A MORE PROATHEROGENIC plasma lipid profile, including greater plasma triglyceride (TG) and total and low-density lipoprotein (LDL)-cholesterol concentrations, lower high-density lipoprotein (HDL)-cholesterol concentration, and smaller HDL particles, than women (24, 25). Sex differences in the plasma lipid profile have traditionally been attributed to differences in the sex hormone milieu; particularly the availability of estradiol, but also progesterone. However, we and others have shown that changes in ovarian steroid concentration during the normal menstrual cycle (26) and after menopause (6, 23, 50) are not associated with changes in very-low-density lipoprotein (VLDL)-TG and VLDL-apolipoprotein B-100 (apoB-100) kinetics and concentrations that ...

Systemic Delivery of Estradiol, but not Testosterone or Progesterone, Alters Very Low Density Lipoprotein-Triglyceride Kinetics in Postmenopausal Women

“…In men, T delivered orally or systemically has no effect on TG concentration (1, 8 -13), possibly because of the high baseline availability of T. In women, the results are equivocal. We have shown that transdermally delivered T has no effect on VLDL-TG kinetics and plasma TG concentration in premenopausal women (14) whereas different T preparations given orally have been found to decrease, increase, or have no effect on plasma TG concentration in postmenopausal women (15,16).…”

“…Blood samples to determine plasma glucose, insulin, FFA, and VLDL-TG concentrations were collected, prepared, and analyzed as previously described (14,17,19). The TTR of plasma free glycerol, glucose and palmitate, and the TTRs of glycerol and palmitate in VLDL-TG were determined by using electronimpact gas-chromatography mass-spectrometry (MSD 5973 system, Agilent) (14,17).…”

“…In addition, we measured free-fatty acid (FFA) rate of appearance (Ra) in plasma (a major source of fatty acids for VLDL-TG synthesis) (14,17) and glucose Ra, an index of hepatic glucose production, to provide a measure of hepatic insulin sensitivity, an important regulator of hepatic lipoprotein metabolism (18).…”

Proteome-wide muscle protein fractional synthesis rates predict muscle mass gain in response to a selective androgen receptor modulator in rats

“…Testosterone has previously been shown to increase muscle fractional synthesis rates (FSRs) in men (24) and in women (30). However, these studies have typically employed a primed constant infusion of stable isotope-labeled amino acids coupled with muscle biopsies collected over a short period to measure the FSR of mixed-muscle proteins rather than the FSR for individual proteins (9,17,29).…”

Síntese proteica em suínos: como fêmeas, machos não castrados e castrados respondem a este processo?

“…Tendo em consideração o efeito anabólico dos hormônios sexuais, principalmente da testosterona, explica-se porque machos inteiros apresentam maior deposição muscular que fêmeas e machos castrados. Em humanos, trabalhos evidenciaram que a testosterona aumenta a taxa de síntese proteica muscular (Wang et al, 2012). Utilizando a técnica de isótopos estáveis, observaram que homens apresentam PUBVET v.12, n.1, a14, p.1-10, Jan., 2018 taxa de síntese proteica muscular até 30% mais elevada que mulheres.…”