Sex Steroids, Sleep, and Metabolic Dysfunction in Women

Summary

Increased plasma triglyceride concentration is a common feature of the metabolic abnormalities associated with obesity and a major risk factor for cardiovascular disease. Obesity is a major risk factor for two conditions that appear to be increasing in prevalence in women: the polycystic ovary syndrome (PCOS) and sleep disordered breathing. PCOS affects 5-8% of women. Sleep disordered breathing affects up to 10% of women. Obstructive sleep apnea (OSA) is the most common cause for sleep disordered breathing and particularly prevalent in obese women with PCOS (\~50%). Both PCOS and OSA augment the increase in plasma triglyceride (TG) concentration associated with obesity, and the effects of PCOS and OSA on plasma TG concentration appear to be additive. The mechanisms responsible for the adverse effects on plasma TG metabolism are not known. The primary goal of this project, therefore, is to determine the mechanisms responsible for the increase in plasma TG concentration in obese women with PCOS and OSA. It is our general hypothesis that alterations in the hormonal milieu that are characteristic of these two conditions are, at least in part, responsible for the increase in plasma TG concentration in obese women with the conditions. Furthermore, we hypothesize that the hormonal aberrations characteristic of the two conditions are particularly harmful to obese, compared with lean, women. The effects of PCOS on skeletal muscle protein metabolism are also not known. However, sex hormones are thought to be important regulators of muscle protein turnover suggesting that muscle protein metabolism is likely to be affected by PCOS. We will examine this by determining the effect of individual sex hormones on muscle protein metabolism and hypothesize that testosterone administration will stimulate muscle protein metabolism while estrogen and progesterone administration will inhibit muscle protein metabolism.

Timeline

Start

2007-09

Primary completion

2013-03

Completion

2013-03

Publications

• Results Wang X, Magkos F, Patterson BW, Reeds DN, Kampelman J, Mittendorfer B. Low-dose dexamethasone administration for 3 weeks favorably affects plasma HDL concentration and composition but does not affect very low-density lipoprotein kinetics. Eur J Endocrinol. 2012 Aug;167(2):217-23. doi: 10.1530/EJE-12-0180. Epub 2012 May 22.
• Results 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. 2012 Mar 15;302(6):E740-6. doi: 10.1152/ajpendo.00533.2011. Epub 2012 Jan 17.
• Results Smith GI, Reeds DN, Okunade AL, Patterson BW, Mittendorfer B. Systemic delivery of estradiol, but not testosterone or progesterone, alters very low density lipoprotein-triglyceride kinetics in postmenopausal women. J Clin Endocrinol Metab. 2014 Jul;99(7):E1306-10. doi: 10.1210/jc.2013-4470. Epub 2014 Apr 2.
• Results Smith GI, Yoshino J, Reeds DN, Bradley D, Burrows RE, Heisey HD, Moseley AC, Mittendorfer B. Testosterone and progesterone, but not estradiol, stimulate muscle protein synthesis in postmenopausal women. J Clin Endocrinol Metab. 2014 Jan;99(1):256-65. doi: 10.1210/jc.2013-2835. Epub 2013 Dec 20.

Drugs

Indications