Effect of growth hormone on caffeine metabolism in hypophysectomized rats

Two groups of six male Sprague-Dawley hypophysectomized rats (operated on day 0), 8 weeks old, treated by sc tetracosactid (ACTH, 10 micrograms every 24 hr), thyroxine (5 micrograms/100 g every 24 hr) and desmopressin (240 ng/kg/24 hr continuous infusion) received SC either saline (group I) or human growth hormone (hGH, 120 micrograms/24 hr) (group II) continuous infusion. ACTH and thyroxine were administered on days 7-19 and desmopressin and hGH on days 8-19, after surgery. They received po caffeine 4 mg/kg as citrate salt on day 15. The 0-12, 12-24 and 24-48 hr urine samples were collected after caffeine administration. Caffeine and metabolites concentrations in urines were determined using HPLC. Effect on hGH on caffeine metabolism was assessed comparing group I and group II. In 0-48-hr urine, 1-methylxanthine (154 +/- 169 pmol/g) and 3-7-dimethyluric acid (5.57 +/- 19.3 pmol/g) in group II were significantly lower than in group I (391 +/- 340 pmol/g and 262 +/- 338 nmol/g, respectively) (p less than 0.05). Other metabolites (6-amino-5-(N-methyl formylamino)-1,3-dimethyluracil included) excretion was not altered. Total, N3-, N7- and N1-demethylation ratios on 0-48 hr urine were not modified by hGH treatment. However, demethylation ratios on 12-24 and 24-48 hr (N3 + N7 + N1) and on 24-48 hr urine samples (N3 and N7) were significantly reduced in group II (p less than 0.05) suggesting an increase in the rate of appearance of demethylated metabolites during hGH treatment.(ABSTRACT TRUNCATED AT 250 WORDS)