Administration of human insulin-like growth factor-binding protein-1 increases circulating levels of growth hormone in mice.
GH is the major regulator of circulating IGF-I, which, in return, controls pituitary GH secretion by negative feedback. IGF-binding protein-1 (IGFBP-1) is believed to modify this feedback through its effects on free IGF-I. In the present study we investigated the potential influence of IGFBP-1 on GH secretion in the absence or presence of a GH receptor antagonist (GHRA) that specifically blocks peripheral GH action. We administered human (h) IGFBP-1 and GHRA to mice alone or in combination for 2 or 7 d. GHRA was administered in a dose previously shown to block GH action without an effect on circulating GH or IGF-I levels. hIGFBP-1 administration increased stimulated circulating GH levels and serum total IGF-I and IGFBP-3 levels. Coadministration of GHRA abolished the hIGFBP-1-induced increase in serum IGF-I and IGFBP-3 levels, whereas stimulated GH levels remained increased. Free IGF-I levels in serum were unchanged in all treatment groups. In conclusion, GH serum levels increased in response to hIGFBP-1 administration, even in the setting of normal IGF-I levels. This finding suggests a direct involvement of IGFBP-1 in GH secretion.
Cingel-Ristic
Vesna
V
Laboratory of Pediatrics, Subdivision of Molecular Endocrinology, Erasmus Medical Center, 3000 DR Rotterdam, Rotterdam, The Netherlands.
Van Neck
Johan W
JW
Frystyk
Jan
J
Drop
Stenvert L S
SL
Flyvbjerg
Allan
A
D000818:Animals; D001786:Blood Glucose; D004435:Eating; D025461:Feedback, Physiological; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D013006:Growth Hormone / Q000097:blood* / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000097:blood; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000235:genetics / Q000494:pharmacology*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000033:anatomy & histology / Q000378:metabolism; D008099:Liver / Q000033:anatomy & histology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009929:Organ Size
D001786:Blood Glucose; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone