The effect of human growth hormone therapy on L-(methyl-2H3)-leucine turnover and urinary pseudouridine concentration in patients with Ullrich-Turner syndrome.
The effect of daily human growth hormone (hGH) injections (3 I.U./m2/day) on tissue anabolism was determined in six patients with Ullrich-Turner syndrome (XO) (8.7-19 years of age) using novel techniques such as whole body leucine kinetics during continuous infusion of L-(Methyl-2H3)-leucine and urinary pseudouridine (5-ribosyluracil) excretion on the one hand and traditional methods like serum urea and amino acid concentrations on the other. Pseudouridine is only found in ribonucleic acid (RNA) and is neither reincorporated nor catabolically broken down and is therefore considered an ideal index of whole body RNA turnover. The mean L-(Methyl-2H3)-leucine turnover of the six XO patients before hGH was 1.90 +/- 0.15 mumoles/kg per minute. After 3 months of hGH-treatment it had increased in three patients, whereas it had decreased in the other three. The results obtained with the stable isotope technique were correlated with the urinary pseudouridine concentrations (r = 0.68; P < 0.01). The growth rates were positively correlated with leucine turnover (r = 0.63; P < 0.02) and urinary pseudouridine concentration (r = 0.73; P < 0.006) as well as negatively correlated with the serum urea concentrations r = -0.62; P < 0.03). The decrease in the individual serum urea concentrations were tightly correlated with the hGH induced change in growth rate (r = -0.90; P < 0.01). The individual bone ages were negatively correlated with the hGH induced changes in leucine turnover (r = -0.77; P < 0.003) as well as with the urinary pseudouridine concentrations (r = -0.87; P < 0.0002). The hGH effect on leucine and RNA turnover, showing effectiveness only until a developmental age between 11 and 12 years, leads the discussion of the ideal moment of oestrogen supplementation when girls with Ullrich-Turner syndrome are treated with hGH in early adolescence.


CONCLUSIONS
The protein metabolism of patients with Ullrich-Turner syndrome is influenced by hGH in an age dependent manner. In a clinical setting, pseudouridine, an easily determined derivative of ribonucleic acids, may be able to replace the tedious work with expensive stable isotopes when questions related to tissue anabolism are to be answered.
Böhles
H
H
Zentrum der Kinderheilkunde, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt/Main, Germany.
Brendel
L
L
Förster
H
H
Träger
K
K
Vogt
J
J
Georgieff
M
M
D000293:Adolescent; D000328:Adult; D000365:Age Determination by Skeleton; D000597:Amino Acids, Branched-Chain / Q000097:blood; D002648:Child; D005260:Female; D005500:Follow-Up Studies; D013006:Growth Hormone / Q000008:administration & dosage*; D006801:Humans; D007930:Leucine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D011560:Pseudouridine / Q000652:urine*; D012741:Sexual Maturation / Q000187:drug effects; D014316:Tritium; D014424:Turner Syndrome / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*
D000597:Amino Acids, Branched-Chain; D014316:Tritium; D011560:Pseudouridine; C030365:leucine methyl ester; D013006:Growth Hormone; D007930:Leucine