title: GH and GHBP activity and not IGF-1 and its receptor activity express growth velocity reduction during treatment of central precocious puberty by a superactive GNRH analogue.
abstract: We studied six patients with central precocious puberty (CPP) (five girls and one boy, aged 9-14.4 years) before and after 5 and 12 months of treatment with GnRH-A (D-TRP-6-LHRH-depo, DECAPEPTYL Ferring, Sweden), and 14 age-matched prepubertal children serving as controls. GnRH suppressed gonadal sex hormone secretion and arrested the gonadarche development. Growth velocity decreased from 9.8 +/- 1.6 (mean +/- SD) to 4.6 +/- 1.0 cm/year after 1 year of treatment. Basal serum IGF-1 levels of the CPP patients were 35.4 +/- 2.8 nmol/l, which was significantly higher than that of the controls (18.8 +/- 1.9, P = 0.00007). After GnRH-A there was a slight but significant increase in serum IGF-1 levels from 35.4 +/- 2.8 (mean +/- SE) to 40.3 +/- 2.1 nmol/l after 5 months (mean difference of 4.9 +/- 1.7, P = 0.02), reversing to 35.6 +/- 2.8 nmol/l after 12 months. The number of high affinity IGF-1 binding sites on erythrocytes (RBC) in the controls was 3.3 +/- 0.3 sites/cell, similar to that found in the patients before treatment. Following therapy, the number of the binding sites decreased from 4.0 +/- 0.8 (mean +/- SE) to 2.5 +/- 0.6 sites/cell after 5 months (mean difference of -1.4 +/- 0.5, P = 0.01), to 2.7 +/- 0.7 sites/cell after 12 months. Basal levels of plasma GH in the CPP patients were 7.1 +/- 1.3 ng/ml, significantly higher than those of the controls (1.2 +/- 0.2, P = 0.00001). Treatment decreased plasma GH in patients from 7.1 +/- 1.3 to 1.3 +/- 0.3 ng/ml after 5 months (mean difference of -5.8 +/- 1.3, P = 0.003) and to 2.7 +/- 1.5 ng/ml after 12 months. The GH binding protein (GHBP) activity in the controls was 76.2 +/- 6.2% relative specific binding, similar to that of the patients before therapy. The mean basal GHBP activity of the patients increased from 75.5 +/- 7.3 to 101 +/- 6.4% (mean difference of 25.5 +/- 9.7, P = 0.01) after 5 months and to 90.1 +/- 5.6% after 12 months of treatment. In conclusion, plasma GH and its receptor activity are a better indicator of the GnRH-A effect on growth than IGF-1 and its receptor activity.
authors.affiliation: Endocrinology and Diabetes Research Unit, Felsenstein Medical Research Center, Petah Tikva, Israel.
authors.forename: R
authors.initials: R
authors.lastname: Eshet
authors.forename: A
authors.initials: A
authors.lastname: Silbergeld
authors.forename: R
authors.initials: R
authors.lastname: Kauli
authors.forename: L
authors.initials: L
authors.lastname: Lazar
authors.forename: Z
authors.initials: Z
authors.lastname: Laron
mesh_terms: D000293:Adolescent; D002352:Carrier Proteins / Q000187:drug effects / Q000502:physiology*; D002648:Child; D005260:Female; D006128:Growth / Q000187:drug effects* / Q000502:physiology; D013006:Growth Hormone / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000187:drug effects; D008297:Male; D011629:Puberty, Precocious / Q000188:drug therapy* / Q000503:physiopathology*; D011863:Radioimmunoassay; D017526:Receptor, IGF Type 1 / Q000187:drug effects; D017329:Triptorelin Pamoate / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D002352:Carrier Proteins; D017329:Triptorelin Pamoate; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D017526:Receptor, IGF Type 1; C051815:somatotropin-binding protein