IGF-I, IGF-II, 'free' IGF-I and IGF-binding proteins-2 to -6 during high-dose oestrogen treatment in constitutionally tall girls.
OBJECTIVE
To investigate the effect of high-dose oestrogen treatment on IGF-I, IGF-II, free-dissociable IGF-I and the IGF-binding proteins (IGFBP)-2 to -6 in girls with constitutional tall stature.


METHODS
In patient cohort 1, blood samples were drawn before and after 3 months of daily oral treatment with 0.1 mg ethinyloestradiol. In cohort 2, samples were collected at the end of the treatment period and 3 to 6 months afterwards. IGFs and IGFBPs were analysed by specific immunoassays and by Western ligand blot.


RESULTS
Total IGF-I decreased significantly on oestrogen treatment and increased again after oestrogen withdrawal. Ligand blot analysis showed a clear reduction in a 34 kDa band, corresponding to IGFBP-2, and a strong induction of a 24 kDa band, corresponding to the non-glycosylated form of IGFBP-4. These changes were confirmed by specific immunological methods. The serum levels of IGFBP-3, IGFBP-5 and IGFBP-6 remained unchanged during the first 3 months of treatment. In cohort 2, IGFBP-3 and IGFBP-6 increased after oestrogen withdrawal. Free-dissociable IGF-I fell to 35+/-4% during oestrogen therapy and rose again when the treatment was stopped.


CONCLUSIONS
Oestrogens modulate the serum concentrations of several components of the IGF system. The fall in total IGF-I is not explained by a decrease in IGFBPs but probably results from a decreased synthesis.
Rooman
Raoul P A
RP
Department of Pediatrics, Antwerp University Hospital, Edegem, Belgium. raoul.rooman@uza.be
De Beeck
Lieve Op
LO
Martin
Manou
M
Van Doorn
Jaap
J
Mohan
Subburaman
S
Du Caju
Marc V L
MV
D000293:Adolescent; D001824:Body Constitution; D001827:Body Height / Q000187:drug effects*; D002648:Child; D004967:Estrogens / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000378:metabolism; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000378:metabolism; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000378:metabolism; D018976:Insulin-Like Growth Factor Binding Protein 6 / Q000378:metabolism; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D008137:Longitudinal Studies
D004967:Estrogens; 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; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II