Ethinylestradiol and testosterone have divergent effects on circulating IGF system components in adolescents with constitutional tall stature.
OBJECTIVE
Pharmacological doses of estrogens or testosterone are used to limit the final height of girls or boys with constitutional tall stature but the mechanism behind this growth inhibition is still debated. We therefore studied the changes in the circulating components of the insulin-like growth factor (IGF) system during high dose sex steroid therapy.


METHODS
Twenty three girls and twenty boys with constitutional tall stature were treated with 100 microg ethinylestradiol per day or 250 mg testosterone ester every 14 days respectively. In 19 girls and 18 boys, the levels of IGF-I, free IGF-I, IGF-II, acid-labile subunit (ALS) and IGF binding proteins (IGFBP)-2 to -6 were measured before and 3-6 months after the start of therapy (group 1). In 18 girls and 11 boys, samples were collected at the end of therapy and 3 to 6 months afterwards (group 2). Fourteen girls and nine boys belonged to both groups. All parameters were measured by radioimmunoassay or ELISA.


RESULTS
Levels of IGF-I were decreased significantly by estrogen treatment but remained unchanged during testosterone treatment. Free IGF-I decreased during estrogen treatment but increased during testosterone therapy. Estrogens increased IGF-II and testosterone reduced it. The important reduction of IGFBP-2 during estrogen therapy is not reproduced by androgen therapy, neither is the stimulation by estrogens of IGFBP-4. IGFBP-3 is not modulated by either sex steroid. We found that IGFBP-6 is up-regulated by testosterone but not by estrogens; the reverse is true for ALS, which increased during estrogen treatment but remained unchanged during testosterone treatment.


CONCLUSIONS
Our findings demonstrate that androgens and estrogens exert differential effects on the circulating levels of several IGF components.
Rooman
Raoul P A
RP
Department of Pediatrics, Antwerp University Hospital, Belgium. raoul.rooman@ua.ac.be
De Beeck
Lieve Op
LO
Martin
Manou
M
van Doorn
Jaap
J
Mohan
Subburaman
S
Du Caju
Marc V L
MV
D000293:Adolescent; D001827:Body Height; D002352:Carrier Proteins / Q000097:blood; D004997:Ethinyl Estradiol / Q000008:administration & dosage*; D005260:Female; D006023:Glycoproteins / Q000097:blood; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000097:blood; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000097:blood; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000097:blood; D018976:Insulin-Like Growth Factor Binding Protein 6 / Q000097:blood; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D007335:Insulin-Like Growth Factor II / Q000032:analysis*; D008297:Male; D013739:Testosterone / Q000008:administration & dosage*
D002352:Carrier Proteins; D006023:Glycoproteins; D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D018974:Insulin-Like Growth Factor Binding Protein 4; D018975:Insulin-Like Growth Factor Binding Protein 5; D018976:Insulin-Like Growth Factor Binding Protein 6; D018969:Insulin-Like Growth Factor Binding Proteins; C075944:insulin-like growth factor binding protein, acid labile subunit; D013739:Testosterone; D004997:Ethinyl Estradiol; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II