Central Nervous System Sites of Action of an Enkephalin Analogue, (D‐Met², Pro⁵)‐Enkephalinamide, and Naloxone on the Secretion of Five Anterior Pituitary Hormones of Male Rats

Abstract

Central nervous system sites of action of opioid peptides on pituitary hormone secretion were investigated. One nmol of an enkephalin analogue, (D-Met', Pros)-enkephalinamide, and 10 nmol of the opiate antagonist naloxone were injected into ten different regions of the brain of conscious male rats and their effect on the release of five anterior pituitary hormones tested. The injections were made through a special injection cannula which was inserted into the brain through a guide cannula fixed on the skull and implanted into the brain 5 to 7 days earlier. Both compounds injected into the medial septum, medial preoptic area and hypothalamic paraventricular nucleus affected prolactin, growth hormone and luteinizing hormone (LH) secretion. The enkephalin analogue stimulated prolactin and growth hormone and inhibited LH release. Naloxone induced the opposite effect. Drugs given into the hypothalamic ventromedial nucleus caused changes in plasma prolactin and growth hormone levels. Enkephalinamide increased and naloxone decreased plasma concentrations of both hormones. Administration of the compounds into the dorsal raphe area resulted in alterations of prolactin and LH release, the analogue caused elevation of prolactin and inhibition of LH release, whereas the opiate antagonist resulted in opposite changes. Only an LH response was obtained from the hypothalamic dorsomedial nucleus and a growth hormone response from the central amygdala. Also in these cases the enkephalin analogue decreased LH and elevated growth hormone plasma levels, and naloxone brought about a rise in LH and a diminution of growth hormone concentration. None of the regions were effective in inducing a clear-cut adrenocorticotrophin or follicle-stimulating hormone response. The parietal cortex, medial amygdala and the dentate gyrus were entirely ineffective sites. The findings suggest that in the brain there are multiple sites of action of opioids on pituitary trophic hormone secretion and the effective sites are not identical in terms of pituitary hormone response.4 large number of experimental data indicate (1-5) that opioid peptides affect secretion of pituitary trophic hormones. In general, it appears that they stimulate prolactin (PRL) and growth hormone (GH), inhibit the release of gonadotrophins, primarily of luteinizing hormone (LH), and elevate or depress plasma adrenocorticotrophin (ACTH) and thyrotroph hormone levels. These effects can be counteracted by the opiate antagonist naloxone. Although there are some observations indicating a direct action of opioid peptides on the anterior pituitary (6-9), most of the findings suggest that they may exert their influence via the CNS (10-13). Such a view is consistent with the presence of all three families of endogenous opioid peptides (proopiomelanocortin-derived endorphins, enkephalins and dynorphins) and opioid peptide receptors in the brain. The observations that opiate antagonists or opiate receptor blockcrs cause alterations in pituitary trophic hormone secretion suggest that en...