Localization of hypophysiotropic peptides and other biologically active peptides within the brain

Immunohistochemical analysis of hypophysiotropic and other neuropeptides reveals unique and striking neural perikarya, axons, and terminals containing specific peptide immunoreactivity. The hypophysiotropic peptides are most highly concentrated in nerve terminals in the external layer of the median eminence. From this site they may be released and carried via the portal circulation to the adenohypophysis. The occurrence of hypophysiotropic peptides in other areas of the nervous system suggests that they may act, at these sites, as neurotransmitters. Enkephalins, SP, angiotensin II, and cholecystokinin-like immunoreactivity are also found in nerve terminals in the external layer of the median eminence of some species. Although these peptides have not been considered hypophysiotropic hormones, the location of their terminals in the median eminence suggests that they participate indirectly in regulation of anterior pituitary hormone release. This control may be accomplished via axo-axonal influences of terminals containing these peptides upon the terminals containing the genuine hypophysiotropic peptides. An analogous interaction is thought to be exerted by dopamine terminals upon LHRH terminals in the median eminence (39). All of the neuropeptides discussed above are found within neuronal structures in the hypothalamus. Most of these peptides are also found, at least to a limited extent, in the brainstem, spinal cord, and deep nuclei of the telencephalon. Few peptides have been localized in neurons of the cerebral cortex. These include SOM, VIP, and cholecystokinin-like immunoreactivity. The cerebellum, to date, has not been shown to contain significant immunoreactivity for any of the presently identifiable neuropeptides. The demonstration of the coexistence of neuropeptides (SOM and SP) in some monoaminergic (adrenergic and serotonergic) neurons raises questions about the one-neuron-one-transmitter hypothesis. It is presently unknown whether or not such coexistence is widespread in the mammalian nervous system. For those neurons that contain two neuroeffector substances, it will be important to determine whether or not both substances play an active role in the function of the neuron. Finally, the details of the morphological interactions of peptidergic elements with other neuronal systems offer the possibility to understand more completely the circuitry of many regions of the central nervous system.