GROWTH-HORMONE PREVENTS PREDNISOLONE-INDUCED INCREASE IN FUNCTIONAL HEPATIC NITROGEN CLEARANCE IN NORMAL MAN

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 r ats to involve an hepatic element in the form of upregulation of the k inetics of ureagenesis. Likewise, the anabolic action of growth hormon e administration has been shown to involve an hepatic element, just as growth hormone administration has been shown to prevent the protein c atabolic side effects of prednisolone. Whether glucocorticoids increas e the ability of the liver to convert amino-N to urea-N in man, and wh ether growth hormone counteracts any possible effect of glucocorticoid has not been studied. Methods: We measured urea nitrogen synthesis ra tes and blood alpha-amino-N levels before, during, and after a 4-h con stant i.v. infusion of alanine (2 mmol. kg BW-1 . h(-1)). The urea nit rogen synthesis rate was estimated hourly as urinary excretion correct ed 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-t o urea-N, and is denoted the functional hepatic nitrogen clearance. Ei ght normal male subjects (aged 22-28 years; BMI 21.6-26.3 kg/m(2)) wer e randomly studied four times: i) after 4 days of s.c. saline injectio ns, ii) after 4 days of s.c. growth hormone injections (0.1 IU . kg(-1 ) . day(-1)), iii) after 4 days of glucocorticoid administration (50 m g/d) and iv) after 4 days of growth hormone and glucocorticoid adminis tration. All injections were given at 20 00 hours and 25 mg prednisolo ne was given morning and evening. Results: Growth hormone decreased fu nctional 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 clearanc e by 23% (47.7+/-3.3 l/h, p<0.05), while growth hormone plus glucocort icoid 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 mechani sm, as shown by the increased functional hepatic nitrogen clearance. G rowth hormone has the opposite effect, and also neutralises the glucoc orticoid effect when given together with prednisolone. This adds to th e understanding of the development and treatment possibilities of ster oid catabolism.