Background/aims: Glucocorticoid treatment increases urea excretion and leads to negative nitrogen balance. This effect is presumed mainly to reflect actions on tissue protein metabolism, but has been shown in rats to involve an hepatic element in the form of upregulation of the kinetics of ureagenesis. Likewise, the anabolic action of growth hormone administration has been shown to involve an hepatic element, just as growth hormone administration has been shown to prevent the protein catabolic side effects of prednisolone. Whether glucocorticoids increase the ability of the liver to convert amino-N to urea-N in man, and whether growth hormone counteracts any possible effect of glucocorticoid has not been studied.
Methods: We measured urea nitrogen synthesis rates and blood alpha-amino-N levels before, during, and after a 4-h constant i.v. infusion of alanine (2 mmol x kg BW(-1) x h(-1)). The urea nitrogen synthesis rate was estimated hourly as urinary excretion corrected for gut hydrolysis and accumulation in body water. The slope of the linear relationship between urea nitrogen synthesis rate and amino-N concentration represents the hepatic kinetics of conversion of amino- to urea-N, and is denoted the functional hepatic nitrogen clearance. Eight normal male subjects (aged 22-28 years; BMI 21.6-26.3 kg/m2) were randomly studied four times: i) after 4 days of s.c. saline injections, ii) after 4 days of s.c. growth hormone injections (0.1 IU x kg(-1) x day(-1)), iii) after 4 days of glucocorticoid administration (50 mg/d) and iv) after 4 days of growth hormone and glucocorticoid administration. All injections were given at 20 00 hours and 25 mg prednisolone was given morning and evening.
Results: Growth hormone decreased functional hepatic nitrogen clearance (l/h) by 21% (from 38.8+/-1.8 l/h (control) to 30.5+/-2.7 l/h (4 d growth hormone) (mean+/-SE) (ANOVA; p<0.05)). Glucocorticoid increased functional hepatic nitrogen clearance by 23% (47.7+/-3.3 l/h, p<0.05), while growth hormone plus glucocorticoid offset any effect on functional hepatic nitrogen clearance (36.2+/-3.3 l/h, p=0.83).
Conclusions: Glucocorticoid administration leads to loss of nitrogen as urea, in part due to a specific hepatic mechanism, as shown by the increased functional hepatic nitrogen clearance. Growth hormone has the opposite effect, and also neutralises the glucocorticoid effect when given together with prednisolone. This adds to the understanding of the development and treatment possibilities of steroid catabolism.