30. Van Soeren M, Graham T: Effect of caffeine on metabolism, exercise endurance, and catecholamine responses after withdrawal. J Appl Physiol 1998, 85:1493–1501.PubMed 31. Kaplan GB, Greenblatt DJ, Kent MA, Cotreau-Bibbo MM: Caffeine treatment and withdrawal in mice: relationships between dosage, find more concentrations, locomotor activity and A1 adenosine receptor binding. J Pharmacol Exp Ther 1993, 266:1563–1572.PubMed Competing interests The authors declare that they have no competing of interests. Authors’ contributions HB, LRA, MVC and ESC were significant manuscript

writers; HB, LRA and ESC participated in the concept and design; HB and MVC were responsible for data acquisition; HB, LRA, MVC and ESC participated in data analysis and interpretation. HKI-272 in vivo All authors read and approved the final manuscript.”
“Background Aging is associated with a decline in a variety of endocrine functions including menopause in women and a deterioration in androgen production in men [1]. Gradual reductions in testosterone levels can lead to many symptoms of andropause including a lack of energy, decreased mental acuity, a loss of overall well-being, and sexual dysfunction [2–4]. Androgen deficiency in aging men IWP-2 purchase may also occur concomitantly with a geriatric

syndrome called sarcopenia or the loss of significant amounts of lean skeletal muscle mass [5]. Sarcopenia is significantly associated with a variety of adverse outcomes which can result in increased incidences of slips, trips and falls leading to bone fractures, hospitalization and physical disability leading to a poor quality of life [6]. Although the causal factors leading to sarcopenia are complex and multifactorial, there is a clear association between age-related decreases in testosterone levels and increased incidences of sarcopenia [2,6]. In males, testosterone is predominantly

synthesized by Leydig cells of the testes using the steroid biosynthesis pathway. Testosterone acts on target cells expressing the androgen receptor to induce changes in gene expression related to the anabolic growth of muscle and an increase bone density, C59 ic50 as well as the androgenic maturation of sex organs. Testosterone levels are directly regulated by 5α-reductase, an enzyme which catalyzes and regulates the synthesis of the more potent androgenic steroid hormone dihydrotestosterone (DHT) from free testosterone, and aromatase, an enzyme that directly converts testosterone into the estrogenic steroid hormone estradiol [7]. As men age, bioavailable levels of testosterone decrease by 2% per year after age 30 [8]. Given the role of testosterone in directly increasing the synthesis of muscle protein and counteracting the catabolic effects of the hormone cortisol in breaking down muscle, researchers and clinicians have developed a variety of pharmacological treatment modalities that aim to increase serum testosterone levels.