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.

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doi.org/10.1210/en.2003-1742, hdl.handle.net/1765/13400
Endocrinology
Erasmus MC: University Medical Center Rotterdam

Cingel-Ristic, V., van Neck, H., Frystyk, J., Drop, S., & Flyvbjerg, A. (2004). Administration of human insulin-like growth factor-binding protein-1 increases circulating levels of growth hormone in mice. Endocrinology, 145(9), 4401–4407. doi:10.1210/en.2003-1742