Suppression of sex steroids by a gonadotrophin-releasing hormone agonist increases serum growth hormone-binding protein activity in girls with central idiopathic precocious puberty.
OBJECTIVE
The high-affinity growth hormone (GH)-binding protein corresponds to the extracellular domain of GH receptor. The direct role of sex steroids in pubertal bone growth may be an increased GH receptor-coupled GH action. We examine the GH-binding protein (GHBP) activity before and after the suppression of female sex steroids and the relation of GHBP to pubertal growth.


METHODS
We studied six girls with central idiopathic sexual precocity without any prior gonadal suppression therapy.


METHODS
We measured GHBP activity before and 12, 24 and 48 weeks after the treatment with s.c. injection of a GnRH agonist (leuprolide acetate) every 4 weeks.


METHODS
GHBP activity was measured by immunoprecipitation using anti-GH receptor monoclonal antibody.


RESULTS
The treatment caused a decrease in the LH and FSH responses to GnRH test and plasma oestradiol, which resulted in decreased urinary GH excretion, plasma IGF-I levels, height velocity and bone age maturation. GHBP activity before the start of the treatment was normal (75 +/- 27% relative to adult pooled serum, mean +/- SD), and it was increased above adult level (122 +/- 29% at 48 weeks, P < 0.01) by the suppression of the pituitary-gonadal axis. There were significant negative correlations between GHBP and oestradiol (r = 0.452, n = 24, P < 0.05) and between GHBP and urine GH excretion (r = -0.462, n = 24, P < 0.05).


CONCLUSIONS
The high-affinity GHBP is increased by the withdrawal of female sex steroid. The clinical significance of this finding may be interference with the binding of GH to its receptor resulting in a reduced IGF-I level and decreased height velocity. The mechanism warrants further study.
Kobayashi
Y
Y
Department of Paediatrics, Chiba University School of Medicine, Japan.
Murata
A
A
Yasuda
T
T
Minagawa
M
M
Wataki
K
K
Ohnishi
H
H
Niimi
H
H
D001827:Body Height / Q000187:drug effects; D002352:Carrier Proteins / Q000097:blood / Q000187:drug effects*; D002648:Child; D002675:Child, Preschool; D004958:Estradiol / Q000097:blood*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006065:Gonadotropins, Pituitary / Q000097:blood*; D013006:Growth Hormone / Q000652:urine; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000187:drug effects; D016729:Leuprolide / Q000494:pharmacology*; D007986:Luteinizing Hormone / Q000097:blood; D011629:Puberty, Precocious / Q000097:blood*
D002352:Carrier Proteins; D006065:Gonadotropins, Pituitary; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D013006:Growth Hormone; D016729:Leuprolide; C051815:somatotropin-binding protein