Effects of growth hormone deficiency and rhGH replacement therapy on the 6beta-hydroxycortisol/free cortisol ratio, a marker of CYP3A activity, in growth hormone-deficient children.
OBJECTIVE
To determine the effect of both growth hormone deficiency (GHD) and rhGH replacement therapy on CYP3A activity as well as the potential influence of gender.


METHODS
The sample consisted of 35 GHD children (16 males and 19 females), aged 2.9-13.1 years, and a control group of 35 healthy children matched for age and sex. The urinary ratio 6beta-hydroxycortisol/free cortisol was used as a marker of CYP3A activity. In patients, urine samples were collected at two times, prior to starting rhGH replacement treatment and 30 days after beginning therapy.


RESULTS
A significantly higher metabolic activity in GHD children was observed in relation to controls ( P=0.0001) without sex differences. Paired comparisons demonstrated a sexually dimorphic effect of rhGH therapy on the CYP3A activity. While boys displayed a significant decrease ( P=0.003), girls showed no significantly different values of CYP3A marker ( P>0.05). Unpaired comparison between controls and GHD children after therapy demonstrated absence of significant differences in boys ( P>0.05) and a strikingly higher activity in girls ( P=0.0001).


CONCLUSIONS
The data suggests that: (a) GHD in children increases CYP3A activity in a non-sex-dependent manner, (b) rhGH treatment for 30 days to GHD children results in a sexually dimorphic effect on CYP3A activity, with a significant decrease in males toward normalization in relation to controls and non-significant changes in females. The results of this study may have important clinical implications for GHD children, since changes in CYP3A activity importantly affect the metabolism of both steroid hormones and CYP3A substrate drugs.
Sinués
Blanca
B
Clinical Pharmacology Unit, Medicine School, University of Zaragoza, Domingo Miral s/n, 50009, Zaragoza, Spain. bsinues@unizar.es
Mayayo
Esteban
E
Fanlo
Ana
A
Mayayo
Esteban
E
Bernal
María L
ML
Bocos
Pilar
P
Bello
Elena
E
Labarta
Jose I
JI
Ferrández-Longás
Angel
A
D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D004393:Dwarfism, Pituitary / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000652:urine; D005260:Female; D019382:Human Growth Hormone / Q000008:administration & dosage / Q000172:deficiency* / Q000627:therapeutic use; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives* / Q000652:urine; D008297:Male; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use
D011994:Recombinant Proteins; D019382:Human Growth Hormone; C001380:6 beta-hydroxycortisol; D003577:Cytochrome P-450 Enzyme System; D006854:Hydrocortisone