IMPACT OF SUPRAPHARMACOLOGICAL ANDROGENIC STEROID-ADMINISTRATION ON BASAL AND INSULIN-STIMULATED GLUCOSE AND AMINO-ACID-METABOLISM

Effects of androgenic steroids at doses used by athletes were studied in a canine model system in which dosage, diet, and activity were cont rolled. Dogs were treated with 19-nortestosterone (200 mg/wk intramusc ularly) or vehicle and were studied at 18 (n = 4 in steroid and vehicl e) or 32 (n = 6 in steroid and n = 4 in vehicle) days. A laparotomy wa s performed under general anesthesia 17 days before experimentation, a nd 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 cla mp (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 ea ch step. Glucose and leucine kinetics were assessed with H-3 glucose a nd C-14-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 i n steroid and vehicle groups (3.9 +/- 0.3 v 3.6 +/- 0.3 mg/kg min, res pectively), but was elevated in the steroid group at 32 days (5.4 +/- 0.5 v 3.2 +/- 0.4 mg/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 +/- 1.4 mU/kg min). Immunoreactive insulin-independe nt glucose utilization (R(d)) was unaffected at 18 days of steroid tre atment, but was increased by almost fourfold at 32 days. Submaximal (6 .4 +/- 1.8 v 9.8 +/- 1.2 mg/kg.min at 2 mU/kg min) and maximal (10.1 /- 0.9 v 19.4 +/- 1.8 mg/kg min) immunoreactive insulin-stimulated glu cose R(d)s were reduced at 32 days in the steroid group compared with the vehicle group. Plasma leucine levels were similar in the basal sta te and were suppressed equally with immunoreactive insulin in steroid and vehicle groups at 18 and 32 days. In addition, basal and immunorea ctive insulin-stimulated leucine kinetics and metabolic fate (oxidatio n and protein synthesis) were not affected by steroid treatment. In su mmary, suprapharmacological doses of the androgenic steroid 19-nortest osterone (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 glu cose fluxes, (3) diminishes insulin-dependent but increases insulin-in dependent glucose Rd, and (4) has no influence on whole-body leucine f lux or the specific metabolic pathways by which this amino acid is dis posed. Copyright (C) 1994 by W.B. Saunders Company