Rapid stimulatory effects of testosterone upon myotubule metabolism and sugar transport,as assessed by silicon microphysiometry

A considerable number of studies have revealed behavioral circumstances that give rise to small or transient differences in circulating testosterone concentrations; however, careful consideration of androgen physiology leads to the disquieting conclusion that these differences are often unlikely to have much physiologic or behavioral significance. In the present report, we observe that small transients of testosterone secretion could have very rapid anabolic effects on a cultured muscle-derived cell line. Specifically, we have examined the effects of testosterone on metabolism in cultured C2C12 myotubules, using a silicon microphysiometer. The instrument monitors cellular extrusion of protons and acidic metabolites, and such extrusion is directly linked to ATP hydrolysis, thus providing a real-time measure of cellular metabolism. Testosterone caused a small but significant increase in metabolism. The most striking feature of this effect was its rapidity, in that it occurred within 3 hr. This rapid enhancement of metabolism suggested that testosterone might be enhancing substrate uptake even more rapidly. Indeed, we found that testosterone increased 2-deoxyglucose uptake within 1 min. The rapidity of this effect seemed to preclude mediation by classical intracellular steroid receptors. In support of this, we were unable to detect specific intracellular binding of testosterone. These findings show that testosterone can exert rapid anabolic effects on substrate transport and metabolism in myotubules. Should this finding general to muscle in vivo, it suggests that relatively small individual differences in testosterone profiles, in response to various social interactions, may have very real consequence for subsequent muscle physiology. © 1996 Wiley-Liss, Inc.