Effects of long-term growth hormone (GH) and triiodothyronine (T3) administration on functional hepatic nitrogen clearance in normal man.
OBJECTIVE
A decline in urea excretion is seen following long-term growth hormone administration, reflecting overall protein anabolism. Conversely, hyperthyroidism is characterized by increased urea synthesis and negative nitrogen metabolism. These seemingly opposite effects are presumed to reflect different actions on peripheral protein metabolism. The extent to which these hormonal systems have different direct effects on hepatic urea genesis has not been fully characterized.


METHODS
We measured urea nitrogen synthesis rates and blood alanine levels concomitantly before, during, and after a 4-h constant intravenous infusion of alanine (2 mmol.kg bw-1.h-1). 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 alanine concentration represents the liver function as to conversion of amino-N, and is denoted the functional hepatic nitrogen clearance. Eight normal male subjects (age 21-27 years; body mass index 22.4-27.0 kg/m2) were randomly studied four times: 1) after 10 days of subcutaneous saline injections, 2) after 10 days of subcutaneous growth hormone injections (0.1 IU/kg per day), 3) after 10 days of triiodothyronine administration (40 micrograms on even dates, 20 micrograms on uneven dates) and 4) after 10 days given 2)+3). All injections were given at 20 00 h.


RESULTS
Growth hormone decreased functional hepatic nitrogen clearance (l/h) by 30% (from 33.8 +/- 3.2 l/h (control) to 23.8 +/- 1.5 l/h (10 days growth hormone) (mean +/- SE) (ANOVA; p < 0.01)). Triiodothyronine did not change functional hepatic nitrogen clearance (36.7 +/- 3.2 l/h), but triiodothyronine given together with growth hormone abolished the effect of growth hormone functional hepatic nitrogen clearance (38.8 +/- 4.8 l/h).


CONCLUSIONS
The results show that long-term growth hormone administration acts on liver by decreasing functional hepatic nitrogen clearance, thereby retaining amino-N in the body. Triiodothyronine has no effect on functional hepatic nitrogen clearance, but given together with growth hormone, it abolishes the effect of growth hormone on functional hepatic nitrogen clearance. A possible mechanism is the known effect of thyroid hormones in reducing the bioavailability of insulin-like growth factor-I. Thus, the effects of growth hormone and triiodothyronine on amino-N homeostasis are interdependent and to some extent exerted via interplay in their regulation of liver function as to amino-N conversion.
Wolthers
T
T
Department of Medicine M (Endocrinology and Diabetes), Aarhus University Hospital, Denmark.
Grøfte
T
T
Møller
N
N
Vilstrup
H
H
Jørgensen
J O
JO
D000328:Adult; D000409:Alanine / Q000008:administration & dosage / Q000097:blood; D000704:Analysis of Variance; D001786:Blood Glucose / Q000378:metabolism; D004338:Drug Combinations; D015200:Fluoroimmunoassay; D013006:Growth Hormone / Q000008:administration & dosage*; D006801:Humans; D007328:Insulin / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009584:Nitrogen / Q000378:metabolism*; D014284:Triiodothyronine / Q000008:administration & dosage*; D014508:Urea / Q000378:metabolism
D001786:Blood Glucose; D004338:Drug Combinations; D007328:Insulin; D014284:Triiodothyronine; D014508:Urea; D013006:Growth Hormone; D009584:Nitrogen; D000409:Alanine