Impact of suprapharmacological androgenic steroid administration on basal and insulin-stimulated glucose and amino acid metabolism

Abstract

Effects of androgenic steroids at doses used by athletes were studied in a canine model system in which dosage, diet, and activity were controlled. Dogs were treated with 19-nortestosterone (200 mg/wk intramuscularly) or vehicle and were studied at 18 (n = 4 in steroid and vehicle) or 32 (n = 6 in steroid and n = 4 in vehicle) days. A laparotomy was performed under general anesthesia 17 days before experimentation, and catheters were placed in an artery, portal vein, and hepatic vein. Studies consisted of an equilibration (120 minutes) and a control (40 minutes) period and a three-step immunoreactive insulin euglycemic clamp (1, 2, and 15 mU/kg·min). Step 1 was 150 minutes, and steps 2 and 3 were 90 minutes. Data were collected during the last 30 minutes of each step. Glucose and leucine kinetics were assessed with 3H-glucose and 14C-leucine. Plasma glucose in steroid and vehicle groups was 104 ± 5 (mean ± SE) versus 108 ± 3 mg/dL and 100 ± 5 versus 107 ± 4 mg/dL at 18 and 32 days. Glucose turnover was similar at 18 days in steroid and vehicle groups (3.9 ± 0.3 v 3.6 ± 0.3mg/kg·min, respectively), but was elevated in the steroid group at 32 days (5.4 ± 0.5 v 3.2 ± 0.4mg/kg·min). Glucose infusion rates were lower in the steroid group with 15 mU/kg·min immunoreactive insulin at 32 days (15.0 ± 1.1 v 21.2 ± 1.4mU/kg·min). Immunoreactive insulin-independent glucose utilization (R d) was unaffected at 18 days of steroid treatment, but was increased by almost fourfold at 32 days. Submaximal (6.4 ± 1.8 v 9.8 ± 1.2mg/kg·min at 2 mU/kg·min) and maximal (10.1 ± 0.9 v 19.4 ± 1.8mg/kg·min) immunoreactive insulin-stimulated glucose R ds were reduced at 32 days in the steroid group compared with the vehicle group. Plasma leucine levels were similar in the basal state and were suppressed equally with immunoreactive insulin in steroid and vehicle groups at 18 and 32 days. In addition, basal and immunoreactive insulin-stimulated leucine kinetics and metabolic fate (oxidation and protein synthesis) were not affected by steroid treatment. In summary, suprapharmacological doses of the androgenic steroid 19-nortestosterone (1) influence glucose kinetics in a manner that is dependent on the duration of exposure, since effects were present at 32 but not at 18 days. After 32 days, 19-nortestosterone (2) stimulates basal glucose fluxes, (3) diminishes insulin-dependent but increases insulin-independent glucose R d, and (4) has no influence on whole-body leucine flux or the specific metabolic pathways by which this amino acid is disposed.