IGF FEEDBACK EFFECTS ON GROWTH-HORMONE SECRETION IN EWES - EVIDENCE FOR ACTION AT THE PITUITARY BUT NOT THE HYPOTHALAMIC LEVEL

The putative negative feedback effects of IGF-I and IGF-II on GH secre tion were tested by intracerebroventricular (icy) and intrapituitary a dministration to sheep. Over two consecutive days, serial jugular bloo d samples were taken at 10 min intervals for 6 h from ewes (n=3/group) fitted with indwelling stainless steel cannulae into the lateral or t hird cerebral ventricles. The sheep were injected (icy) with either ve hicle or purified ovine IGF-I (2, 4 or 8 mu g). IGF-I injection had no effect on plasma GH secretion. Serial blood samples were taken from a second group of nine ewes in which ovine or recombinant human (rh) IG F-I was infused (2.5 mu g/h for 2 h) into the third ventricle; once ag ain, IGF-I failed to affect the episodic pattern of GH secretion. Thre e ewes fitted with indwelling stainless steel cannulae placed in the a nterior pituitary gland were consecutively infused with either ovine o r rhIGF-I (2.5 mu g/h for 2 h) or vehicle. Plasma GH concentrations we re suppressed in 3/3 sheep from 1-1.5 h after the commencement of infu sion and GH levels remained low for the remainder of the sampling peri od. In another group of five ewes synergistic effects of IGF-I and IGF -II on GH secretion were tested by icy infusion of rhIGF-I, rhIGF-II, or rhIGF-I+rhIGF-II (5 mu g/h for 2 h) or vehicle (sterile 10 mM HCl/s aline). Each sheep received each treatment in a randomised design. Inf usion (icy) of IGF-I and IGF-II alone or in combination failed to alte r GH secretion. These observations suggest that IGF-I derived from per ipheral tissues may modulate GH release at the pituitary level but tha t IGF-I acts neither alone nor in conjunction with IGF-II as a negativ e feedback regulator of GH secretion via the hypothalamus in the ewe.