INTRACEREBRAL ADMINISTRATION OF INSULIN-LIKE GROWTH FACTOR-I DECREASES CIRCULATING GROWTH-HORMONE LEVELS IN THE FETAL PIG

Radioimmunoassayable IGF-I levels were measured in the cerebrospinal fluid and plasma of pig fetuses at 94 days gestational age. Mean plasma IGF-I levels were 128.5 +/- 5.8-mu-g/l while the concentration in the cerebrospinal fluid was 25.8 +/- 4.4-mu-g/l. The effect of intracerebroventricular administration of IGF-I on circulating GH levels was also studied in pig fetuses in utero. Eighteen pig fetuses were fitted with indwelling carotid artery and jugular vein catheters. Nine fetuses were given 1500 ng of pure IGF-I in 100-mu-l 0.9% saline by direct injection into a right lateral ventricle. Nine further fetuses (controls) were similarly given 100-mu-l of saline without IGF-I. GH levels in the control fetuses were approximately 200-mu-g/l and showed marked fluctuations with episodic intervals of about 40 min. By contrast, in the IGF-I-treated fetuses, GH levels were dramatically lowered by 20 min after IGF administration and remained low throughout the 4-h study. The episodic variations in GH were abolished and levels remained fairly constant at ca. 40-mu-g/l. From these results we surmise that the low levels of IGF-I in the fetus may contribute to their high GH levels. At this stage it is not possible to identify whether the IGF-I inhibition is a direct effect on the pituitary or is mediated by increased somatostatin, decreased GHRH or both.