Metab Brain Dis DOI 10.1007/s11011-015-9655-3

REVIEW ARTICLE

Testosterone deficiency, insulin-resistant obesity and cognitive function Hiranya Pintana & Nipon Chattipakorn & Siriporn Chattipakorn

Received: 27 August 2014 / Accepted: 3 February 2015 # Springer Science+Business Media New York 2015

Abstract Testosterone is an androgenic steroid hormone, which plays an important role in the regulation of male reproduction and behaviors, as well as in the maintenance of insulin sensitivity. Several studies showed that testosterone exerted beneficial effects in brain function, including preventing neuronal cell death, balancing brain oxidative stress and antioxidant activity, improving synaptic plasticity and involving cognitive formation. Although previous studies showed that testosterone deficiency is positively correlated with cognitive impairment and insulin-resistant obesity, several studies demonstrated contradictory findings. Thus, this review comprehensively summarizes the current evidence from in vitro, in vivo and clinical studies of the relationship between testosterone deficiency and insulin-resistant obesity as well as the correlation between either insulin-resistant obesity or testosterone deficiency and cognitive impairment. Controversial reports and the mechanistic insights regarding the roles of testosterone in insulin-resistant obesity and cognitive function are also presented and discussed. Keywords Obesity . Insulin resistance . Testosterone deprivation . Neuroprotective effect . Cognitive function H. Pintana : N. Chattipakorn : S. Chattipakorn (*) Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand e-mail: [email protected] S. Chattipakorn e-mail: [email protected] H. Pintana : N. Chattipakorn Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand S. Chattipakorn Department of Oral Biology and Diagnostic Sciences, Faculty of Dentistry, Chiang Mai University, Chiang Mai 50200, Thailand

Introduction Testosterone is an androgenic sex steroid hormone, synthesized from the endoplasmic reticulum of Leydig cells in testis (95 %) and from the adrenal gland (5 %) (Ewing et al. 1983; Vinson et al. 1976). The synthesis and secretion of testosterone are mainly controlled by the hypothalamic-pituitary-testes axis (HPT axis) (Emanuele and Emanuele 2001; Franchimont et al. 1975; Nunemaker and Satin 2014). There are three different forms of circulating testosterone, including free testosterone (2–3 %), albumin-bound testosterone (20–40 %), and sex hormone-binding globulin (SHBG) bound testosterone (60–80 %) (Betancourt-Albrecht and Cunningham 2003; Kapoor et al. 2005). Free testosterone, an active form of testosterone, is metabolized to be 5α-dihydrotestosterone (DHT) via 5α-reductase enzyme (Janowsky 2006; Li and Al-Azzawi 2009). Free testosterone and DHT directly exert their effects via binding androgen receptors (ARs) in various parts of the body, including reproductive organs, liver, kidney, muscles, bone, heart and brain (Janowsky 2006; Pelletier et al. 2000; Takeda et al. 1990; Volterrani et al. 2012). Under physiological condition, testosterone plays important roles in the development of secondary male sexual characteristics (Schiavi and White 1976), the regulation of glucose and lipid metabolism (Aydilek and Aksakal 2005; Christoffersen et al. 2010), bone growth as well as the modulation of normal brain function, including cognition (Filova et al. 2013; Janowsky 2006; Meydan et al. 2010). However, testosterone can be converted to be estradiol via the aromatase enzyme. Therefore, it implies that testosterone can also activate estrogen receptors (ERs) (Filova et al. 2013; Janowsky 2006; Ogawa et al. 1997). Testosterone deficiency is a low testosterone condition with serum total testosterone levels

Testosterone deficiency, insulin-resistant obesity and cognitive function.

Testosterone is an androgenic steroid hormone, which plays an important role in the regulation of male reproduction and behaviors, as well as in the m...
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