The anabolic steroid methandienone targets the hypothalamic–pituitary–testicular axis and myostatin signaling in a rat training model

Abstract

There is increasing evidence that the biological activity of myostatin (MSTN), a negative regulator of muscle growth, is affected by training but also anabolic steroids. In this study, we analyzed the effects of the frequently abused anabolic steroid methandienone (Md) on the hypothalamic-pituitary-testicular axis and androgen-sensitive tissues in intact rats performing a treadmill training to simulate the situation of abusing athletes. The anabolic effects were correlated with the expression of members of the MSTN signaling cascade. Md treatment resulted in a significant stimulation of anabolic activity of the levator ani muscle, which was further increased by training, while prostate and seminal vesicle weights decreased in conformance with hormone concentrations of LH and testosterone. In gastrocnemius muscle, mRNA expression of genes of the MSTN signaling cascade (MSTN, Smad7 and MyoD) was reduced by training but not after Md treatment, in soleus muscle MSTN and its inhibitors, follistatin (FLST) and Smad-7 were only affected after training in combination with Md treatment. In summary, our data demonstrate that Md treatment of intact rats results in anabolic effects which are enhanced in combination with physical activity. Interestingly, the anabolic activity on the levator ani was increased in combination with training, although the levator ani muscle was not specifically stimulated by our training protocol. In the m. gastrocnemius and soleus, the anabolic effects correlate with changes in the expression patterns of genes involved in MSTN signaling. Our data provide evidence that the decrease in the weight of androgen-sensitive sexual glands, observed after Md treatment, is caused by a suppression of endogenous testosterone synthesis. These observations provide new insights into the molecular mechanisms of the interaction between anabolic steroids, training and MSTN signaling during skeletal muscle adaptation.

Modulation of Follistatin and Myostatin Propeptide by Anabolic Steroids and Gender

“…The role of endogenous testosterone levels on MSTN serum levels during aging is described [ 20 , 25 ] , but to our knowledge no study exists that has investigated the infl uence of exogenous anabolic steroids on serum FOLLI and MYOPRO concentrations in humans. Contrary to recent results obtained from intact rats [ 17 ] where the anabolic steroid methandienone did not alter serum concentrations of FOLLI, here we detected signifi cantly increased FOLLI concentrations in the bodybuilders who had used several types of anabolic steroids (including nandrolone, drostanolone, trenbolone and methandienone) compared to the natural bodybuilders ( • ▶ Fig. 1a ).…”

Androgens Regulate Gene Expression in Avian Skeletal Muscles

“…Prior studies that examine the effects of androgens on the expression of MyoD have given contradictory results [70], which may be due to differences in the examined tissue or muscle type [71]. Our results suggest MyoD is androgen-insensitive in passerine skeletal muscle.…”

Combined effects of androgen anabolic steroids and physical activity on the hypothalamic–pituitary–gonadal axis

“…The decrease of prostate and seminal vesicle weights after 321 exogenous administration of anabolic steroids is a typical 322 indication for an interrupted endogenous testosterone production 323 in the testis. This phenomenon has been described already in 324 previous own studies [26,27] and by other investigators [25,28]. 325 The increase of muscle fiber area of the M. soleus demonstrates 326 that administration of all three substances results in a stimulation 327 of hypertrophy.…”

“…25 a spreading sedentary life style [3]. A scenario of extremely high 26 relevance for the health status of the population is the gradual 27 decrease in the ability to maintain skeletal muscle function and mass 28 during aging (sarcopenia). For these reasons there is an urgent need 29 to develop strategies for prevention or treatment of skeletal muscle 30 loss.…”