PHYSIOLOGICAL SIGNIFICANCE OF NEUROTENSIN IN PITUITARY GLYCOPROTEIN HORMONE-RELEASE AS REVEALED BY IN-VIVO AND IN-VITRO STUDIES WITH NEUROTENSIN ANTISERUM

The neuropeptide, neurotensin, is localized to neurons within the hypo thalamus which project to the median eminence. It is released from the terminals in the median eminence into the hypophyseal portal vessels and is carried to the gland. The content in the pituitary gland cells may be partly related to the delivery of the peptide via the portal ve ssels, but it also appears to be produced directly in pituitary cells. The peptide has actions on the release of glycoprotein hormones from the pituitary and in the present experiments, we attempted to determin e whether these actions of the peptide were physiologically significan t by microinjecting purified antiserum directed against neurotensin in to the third cerebral ventricle or intravenously into conscious freely moving rats. Blood samples were withdrawn from an indwelling intra-ri ght atrial catheter. In ovariectomized rats with high levels of plasma gonadotropins because of removal of ovarian steroid negative feedback , the intraventricular injection of the higher (3 mu l) dose of neurot ensin antiserum (NT-AS) induced a more than 2-fold increase in plasma LH within 2 h which was maintained until 3 h after the injection and r eturned to basal values in the 4th and 5th hour. The lower 1-mu l dose was ineffective and there was no response to the control normal rabbi t serum (NRS) injections into the third ventricle in this and the othe r experiments. When the animals were primed with estrogen and progeste rone to mimic preovulatory conditions, the results were altered in tha t the lower 1-mu l dose of NT-AS produced an increase in plasma LH app arent from 3 to 5 h following injection whereas the 3-mu l dose was in effective. The antiserum induced the opposite response of FSH to that previously described for LH in the ovariectomized animals, namely a si gnificant decrease in plasma FSH following the higher but not the lowe r dose of NT-AS. In the ovariectomized estrogen, progesterone-primed r ats (OEP rats), the antiserum had no effect on plasma FSH. The intrave ntricular injection of either the 1- or 3-mu l dose of NT-AS induced a depression in plasma TSH in the ovariectomized rats apparent from 3 t o 5 h after injection, whereas in the OEP rats, this suppression was s ignificant from 1 to 5 h only with the higher 3-mu l dose. Intravenous injection of the antiserum was ineffective to modify FSH or LH in eit her the ovariectomized or OEP animals; however, intravenous injection of 40 mu l of NT-AS suppressed plasma TSH within 2 h in ovariectomized and intact male rats. There was no effect of NT-AS on the release of FSH, LH or TSH from overnight cultured dispersed pituitary cells of ma le rats. We conclude that neurotensin has a physiologically significan t inhibitory action on the release of LH mediated at the hypothalamic level, presumably by suppressing the release of LHRH. On the other han d, at least in the ovariectomized rat, there is a physiologically sign ificant hypothalamic action of the peptide to stimulate FSH release, i llustrating the differential hypothalamic control of these two hormone s. In contradistinction to these hypothalamic actions of the peptide, neurotensin appears to have a physiologically significant TSH-releasin g action by direct stimulation of the thyrotropes.