In vivo MRI evaluation of anabolic steroid precursor growth effects in a guinea pig model

Abstract

Anabolic steroids are widely used to increase skeletal muscle (SM) mass and improve physical performance. Some dietary supplements also include potent steroid precursors or active steroid analogs such as nandrolone. Our previous study reported the anabolic steroid effects on SM in a castrated guinea pig model with SM measured using a highly quantitative magnetic resonance imaging (MRI) protocol. The aim of the current study was to apply this animal model and in vivo MRI protocol to evaluate the growth effects of four widely used over-the-counter testosterone and nandrolone precursors: 4-androstene-3 17-dione (androstenedione), 4-androstene-3beta 17beta-diol (4-androsdiol), 19-nor-4-androstene-3beta-17beta-diol (bolandiol) and 19-nor-4-androstene-3 17-dione (19-norandrostenedione). The results showed that providing precursor to castrated male guinea pigs led to plasma steroid levels sufficient to maintain normal SM growth. The anabolic growth effects of these specific precursors on individual and total muscle volumes, sexual organs, and total adipose tissue over a 10-week treatment period, in comparison with those in the respective positive control testosterone and nandrolone groups, were documented quantitatively by MRI.

Fig. 1

High-resolution T1-weighted MR imaging provides sufficient soft tissue contrast for detection and quantification of various tissues and organs of interest to evaluate the growth effects of selected anabolic steroids and steroid precursors.

Fig. 2

The circulating steroid levels (in mean ± standard deviation) observed over 7weeks post capsule implantation in various groups for study of dosing effect (i.e., number of capsules) prior to in vivo MRI experiment. Animal sample sizes were 3–4 for each steroid precursor group and control steroid group, respectively.

Fig. 3

The steroid levels measured at baseline, week 5, and week 10 in different experimental groups during the in vivo MRI study. Difference from baseline: *p < 0.05 and **p < 0.01. Abbreviations: Testo: testosterone; Andros: androstenedione; 4-Andros: 4-androstenediol;Nandro: nandrolone; 19-Nor.: 19-norandrostenedione.

Fig. 4

The tissue and organ volumes measured at baseline and 10-week time points for the intact and castrated groups in response to the empty, control steroid, and respective steroid precursor replacement, demonstrating the growth effects of the steroid precursor replacements on the muscle compartments, and the prostate and seminal vesicle tissues. Difference from baseline: *p < 0.05 and **p < 0.01.

Fig. 5

The total skeletal muscle, adipose tissue, and body weight measured at baseline and 10-week time points for the intact and castrated groups in response to empty capsule, steroid, and respective steroid precursor capsule replacement. Difference from baseline: *p < 0.05 and **p < 0.01.

Fig. 6

The testes volumes measured at baseline and 10-week time points for the intact groups in response to empty capsule, steroid, and respective steroid precursor capsule replacement. Difference from baseline: *p < 0.05 and **p < 0.01.

Fig. 7

MRI muscle distribution (rostral to caudal) in intact empty, castrated empty, castrated steroid, and castrated steroid precursor capsule replacement groups at the 10-week endpoint.