Recent studies on the role of brain peptides in control of anterior pituitary hormone secretion

Abstract Recent work in our laboratory on the role of peptides to influence release of pituitary hormones by direct action on the gland and also some of the interactions of these peptides at the hypothalamic level to alter release of pituitary hormones will be reviewed. Considerable evidence from hypothalamic stimulation and lesion studies suggests the existence of a separate FSH-releasing factor (FSHRF). We have been able to purify a bioactive FSHRF which appears to be distinct from LHRH. Consequently, we believe that a distinct FSHRF will ultimately be isolated. With regard to prolactin, it is now clear that it is under dual control by both prolactin-inhibiting (PI) and prolactin-releasing factors (PRF). Although dopamine acts as a PIF, our recent fractionation studies indicate the existence of a peptidic PIF in hypothalamic extracts which can be separated from dopamine and GABA. The peptidic PIF is eluted from Sephadex in the same position originally described by us a number of years ago. Thus, inhibitory control is probably mediated by a combination of factors which would include dopamine, possibly GABA and a peptidic PIF. A number of peptides have been shown to have PRF activity which include TRF and also VIP. In recent studies, we have shown a prolactin-releasing action of oxytocin on male hemipituitaries or dispersed pituitary cells. Furthermore, high doses of oxytocin given intravenously released prolactin in male rats. There is a correlation between estrogen-induced prolactin release and an increase in plasma oxytocin and a correlation between suckling-induced oxytocin and prolactin release. These results suggest that oxytocin may be an important PRF. Control of growth hormone (GH) secretion is similarly under dual control via panhibin (somatostatin) and GRF. We have recently shown that motilin can stimulate release of GH from hemipituitaries or dispersed pituitary cells in vitro and that large doses are also effective in vivo . Furthermore, antisera raised against motilin were capable of lowering plasma GH. Motilin has been found in the median eminence and also in somatotrophs. Therefore, these results suggest that motilin may be a physiologically important GRF. In the meantime, a tumor (t) GRF has been synthesized by two laboratories and is extremely potent to release GH in vivo and in vitro . This peptide is much more potent than motilin and has an additive effect with motilin to increase GH release in vitro . We also have evidence for an important interplay amongst the various releasing and inhibiting factors at the hypothalamic level. For example, somatostatin injected into the ventricle will elevate GH instead of lowering it. This action is probably due to an ultrashort loop feedback to suppress somatostatin release and/or also stimulate GRF release. Similarly, peptides which stimulate prolactin release via direct action on the pituitary tend to inhibit it when given intraventricularly. Motilin, which stimulates GH release when given systemically, inhibits it when given intraventricularly and we have found similar results with synthetic GRF, low doses of which given intraventricularly suppress instead of stimulating GH release.