Role of insulin-like growth factor I in regulating growth hormone release and feedback in the male rat.
In vivo and in vitro (static incubation and perifusion) procedures were used to examine the role of insulin-like growth factors (IGFs) in growth hormone (GH) feedback. An alpha 2-adrenergic agonist, clonidine (CLON; 2 x 10(-8) M in vitro or 30 micrograms/ml/kg body weight i.v. in vivo), which mimics the hypothalamic mechanism triggering GH release, was injected to induce a GH surge. Feedback was initiated by human GH (hGH; 2 x 10(-6) M) in vitro or ovine GH (oGH) (20 micrograms/2 microliters intraventricularly) in vivo. GH-releasing factor (GRF; 1 x 10(-8) M) was added at the end of in vitro experiments to test pituitary responsiveness. The involvement of somatostatin (SRIF), GRF and IGFs in mediating GH feedback was evaluated in hypothalamic-pituitary coperifusion. CLON-induced GH release in this system was associated with increased GRF and decreased SRIF release, and the pattern was reversed by hGH. The influence of hGH was mimicked by IGF-I (1.5 x 10(-8) M), except that the GH release was depressed below baseline levels, suggesting a direct effect of IGF-I on the pituitary. Furthermore, the inhibitory effect of hGH on the CLON-induced GH surge and hypothalamic releasing factors (increased SRIF and decreased GRF) was reversed by antisera to IGF-I (1:100), IGF-II (1:100), or both. To determine whether IGF-I is released from hypothalamus or pituitary in response to GH, tissues were tested separately in static incubation. As compared with basal levels, incubation of hypothalami with hGH increased IGF-I and SRIF and decreased GRF release. Because GH and IGF-I release remained unchanged when pituitaries were incubated alone with hGH, the site of IGF-I release and GH feedback is most likely at the hypothalamic level. To evaluate the role of IGFs on GH feedback in vivo, male rats were prepared with permanently implanted 3rd-ventricular and jugular cannulae. CLON was administered intravenously, and oGH, IGF-I (0.5 microgram/2 microliters), and IGF-I and -II antisera (1:100) were injected intraventricularly. In this as in in vitro studies, IGF-I mimicked the inhibitory feedback effect of GH on the CLON-induced GH surge, and IGF antisera blocked GH feedback. We propose that these studies suggest that endogenous hypothalamic IGF-I mediates the influence of GH in the feedback mechanism by increasing SRIF and depressing GRF release.
Becker
K
K
Department of Biological Sciences, Northern Illinois University, De Kalb 60115, USA.
Stegenga
S
S
Conway
S
S
D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D005246:Feedback; D013006:Growth Hormone / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D007031:Hypothalamus / Q000378:metabolism; D007106:Immune Sera / Q000494:pharmacology; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D007335:Insulin-Like Growth Factor II / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D010477:Perfusion; D010902:Pituitary Gland / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000502:physiology
D007106:Immune Sera; D011942:Receptors, Adrenergic, alpha; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D013006:Growth Hormone; D003000:Clonidine