Protein metabolism in acromegaly: differential effects of short- and long-term treatment.
BACKGROUND
GH acutely increases body protein by stimulating protein synthesis and reducing protein oxidation.


OBJECTIVE
The objective of the study was to determine whether these changes in protein metabolism are sustained in long-term GH excess and reversed by correction.


METHODS
We conducted a cross-sectional study in 16 acromegalic and 18 normal subjects and a longitudinal study in which acromegalic subjects were studied before and after short-term (n=8) or long-term (n=10) treatment.


METHODS
The study was conducted at a clinical research center.


METHODS
Whole-body rates of leucine appearance (leucine Ra; an index of protein breakdown), leucine oxidation, and nonoxidative leucine disposal (NOLD; an index of protein synthesis) estimated using infusion of 1-[13C] leucine were measured.


RESULTS
Leucine Ra and NOLD were greater (P<0.01) in acromegalic compared with normal subjects, whereas leucine oxidation did not differ. Leucine oxidation increased significantly (P<0.05) after short-term treatment but returned to baseline after long-term treatment. Both leucine Ra and NOLD decreased significantly (P<0.05) after short- and long-term treatment. Adjustment for body composition did not affect results.


CONCLUSIONS
In acromegalic subjects, protein breakdown and synthesis are increased, whereas protein oxidation does not differ from normal subjects. Protein oxidation increases transiently, whereas protein breakdown and synthesis are stably reduced after treatment. Because protein oxidation represents irreversible loss, we conclude that the normal state of protein oxidation found in acromegaly and after long-term treatment represents metabolic adaptation, which maintains protein mass at a steady state after stable changes in GH status.
Gibney
James
J
Department of Endocrinology, St. Vincent's Hospital, and Garvan Institute of Medical Research, University of New South Wales, Sydney, Australia.
Wolthers
Troels
T
Burt
Morton G
MG
Leung
Kin-Chuen
KC
Umpleby
A Margot
AM
Ho
Ken K Y
KK
D000172:Acromegaly / Q000378:metabolism*; D000328:Adult; D000368:Aged; D001823:Body Composition; D015992:Body Mass Index; D003430:Cross-Sectional Studies; D005091:Exons; D005260:Female; D019382:Human Growth Hormone / Q000235:genetics*; D006801:Humans; D007930:Leucine / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011506:Proteins / Q000378:metabolism*; D012016:Reference Values
D011506:Proteins; D019382:Human Growth Hormone; D007930:Leucine