In Vivo and in Vitro Effects of Substance P and Neurotensin on Gonadotropin and Prolactin Release*

Abstract

Conscious ovariectomized rats bearing a cannula implanted in the third ventricle were injected with 2 μl 0.9% NaCl containing varying doses of substance P (SP) or neurotensin (NT), and plasma gonadotropins and PRL were measured by RIA of jugular blood samples drawn through an indwelling silastic catheter. Control injections of saline iv or into the thirdventricle did not modify plasma hormone levels. Intraventricular injection of NT at doses of either 0.5 or 2 μg lowered plasma LHconcentrations within 5 min and they remained low for 60 min. These doses of NT also lowered plasma PRL with a similar time course. An intermediate dose of 1 μg NT iv had no effect on plasma LH but elevated plasma PRL. Incubation of hemipituitaries from OVX rats with varying doses of NT did not alter gonadotropin release into the medium, but PRL release was enhanced with doses of 50 or more ng/ml medium. It is suggested that NT acts centrally to inhibit LHRH release and to bring about an inhibition of PRL release and that it can act directly on the pituitary to stimulate release of PRL. Intraventricular injection of 0.5- or 2-μg doses of SP induced a significant elevation in plasma LH levels within 5 min of injection, and the values returned toward the preinjection level by 60 min. The elevations were dose related at 15 and 30 min. The lower dose of SP had no effect on plasma PRL levels, but they were elevated significantly within 5 min by a dose of 2 μg. Values remained elevated until 30 min and then declined toward preinjection levels. A l-μg dose of SP injected iv produced an effect on plasma LH opposite to that obtained with intraventricular injection and there was a slight but significant decline at 15 and 30 min. Plasma PRL was elevated by iv SP even more than by a 2-μg dose injected into the ventricle. As in the case of NT, incubation of pituitaries in vitro with SP resulted in an increased PRL release into the medium with doses of 50 or more ng/ml. It would appear that SP can act centrally to stimulate the release of LHRH, which then brings about a release of LH. The elevation in PRL after intraventricular SP may be via a direct action on the pituitary to stimulate PRL release, since it was active in vitro. The results are consistent with central actions of both peptides to alter release of releasing and/or inhibiting hormones and with a direct action on the pituitary to stimulate PRL release.