Effects of Adrenalectomy and Hypophysectomy on Enkephalin Content of the Rat Hypothalamus

Abstract

1Hypothalamic content of enkephalin in rats has been measured by bioassay against methionineenkephalin on field-stimulated mouse vas deferens after acid extraction and purification using Amberlite XAD-2 resin. 2 Surgical stress lowered hypothalamic enkephalin content initially but 6 days after operation the content was higher in sham-operated than in adrenalectomized animals. 3 Corticosteroid replacement therapy showed that hypothalamic enkephalin content was not related directly to circulating corticosteroid levels and that it was increased by the stress of handling and injection.4 Hypothalamic enkephalin content of rats that had undergone hypophysectomy 11 days earlier did not differ from that of intact animals but surgical stress, which lowered content in intact rats and had no effect after adrenalectomy, produced a rise in content in these hypophysectomized animals.5 The ingestion of 0.9% saline, in place of water, by sham-adrenalectomized rats altered the effect of surgical stress on hypothalamic enkephalin content without affecting the resting levels. 6 Of extracts from adrenalectomized rats, 10% contained a substance that behaved atypically on the mouse vas deferens. showing a slower onset and offset of action. The mol. wt. of the substance and sensitivity to naloxone reversal appeared to be similar to enkephalin, but it was resistant to carboxypeptidase-A and protease treatment. 7 It is concluded that the enkephalin content of the hypothalamus is affected by activity in the hypothalamus-pituitary-adrenal system but that it is not related in a simple manner to the levels of corticotrophin releasing hormone, corticotrophin or corticosteroids. IntroductionEnkephalins appear to be neurotransmitters in the brain (Hughes, 1979) and their involvement in the control of the endocrine system is suggested by the ability of morphine to affect anterior pituitary function (George, 1971). There is direct evidence that methionine-enkephalin is capable of increasing plasma concentrations of prolactin (Lien, Fenichel, Garsky, Sarantakis & Grant, 1976) and growth hormone (Dupont, Cusan, Garson, Labrie & Li, 1977) whilst it lowers those of luteinizing hormone and thyrotrophin (Bruni, Van Vugt, Marshall & Meites, 1977). That enkephalins might also be involved in the hypothalamus-pituitary-adrenal (HPA) system is suggested by the enhancement of the corticosterone response to ether stress produced by the intracerebroventricular administration of methionineenkephalin to mice (Gibson, Ginsburg, Hall & Hart, 1979b).Morphine is considered to affect the HPA system by an action in the hypothalamus (George & Way, 1959;Lotti, Kokka & George, 1969). The high content of opioid receptors (Kuhar, Pert & Snyder, 1973) and enkephalin-like immunoreactive material (Elde, Hokfelt, Johanssen & Terenius, 1976) (Table 1). Hypothalami were removed from rats at different times during the day but although the enkephalin content rose between 09 h 30 min and 16 h 00 min the change was not significant. The results in Table I show that there was no...

Leucine‐enkephalin and Methionine‐enkephalin Produce Opposing Effects on Plasma Corticosterone Levels in Ether‐stressed Mice

“…Thus Leu-enkephalin seemed to reinforce the negative feedback mechanisms within the HPA system which are activated by stress (Jones, Hillhouse & Burden, 1976), and produced an effect which opposed that of Met-enkephalin. (Rossier, Guillemin & Bloom, 1978;Gibson, Ginsburg, Hart & Kitchen, 1980). The present results would suggest that activation of Met-enkephalin containing nerves and Leuenkephalin containing nerves would produce opposing effects on the HPA system and therefore that the degree of activation of the system by stress may be dependent upon the balance of activity within the brain of the endogenous opioid peptides.…”

“…It is of interest that Buckingham & Hodges (1979) have recently found that endogenous opioid peptides can produce mutually antagonistic effects on the output of corticotrophin releasing hormone in vitro, and Larssen, Childers & Snyder (1979) have identified distinct Met-enkephalin containing and Leu-enkephalin containing nerve tracts in brain. It is known that various types of stress cause a reduction in hypothalamic enkephalin content, and this has been interpreted as being a result of stress-induced activation of central enkephalin containing nerves (Rossier, Guillemin & Bloom, 1978;Gibson, Ginsburg, Hart & Kitchen, 1980). The present results would suggest that activation of Met-enkephalin containing nerves and Leuenkephalin containing nerves would produce opposing effects on the HPA system and therefore that the degree of activation of the system by stress may be dependent upon the balance of activity within the brain of the endogenous opioid peptides.…”

Developmental responses to opioids reveals a lack of effect on stress‐induced corticosterone levels in neonatal rats

“…In particular there is evidence that stress responses are modulated by opioids. For example footshock alters levels of plasma P-endorphin and hypothalamic [Leu] enkephalin (Rossier et al, 1977;1978) and adrenalectomy lowers the content of hypothalamic opioid peptides (Gibson et al, 1980). In addition the basal and stress-induced secretion of 'Author for correspondence.…”

Stereospecific enhancement of evoked release of brain acetylcholine by narcotic antagonists

“…While the status of the enkephalin or endorphin release in the brain of hypophysectomized animals is unknown, the steady state brain levels of these peptides have been shown in some studies to remain unchanged in such animals (Rossier et al, 1977;Kobayashi etal., 1978;Gibson, Ginsburg, Hart & Kitchen, 1980). The ability of (-)-Nal to reverse the action of the exogenously administered opioid agonists was not affected ir these animals.…”

“…The decreased effect of Nal might be due to a weak enkephalin-mediated inhibition of cholinergic neurones resulting from a diminished release of endogenous opioids. While the status of the enkephalin or endorphin release in the brain of hypophysectomized animals is unknown, the steady state brain levels of these peptides have been shown in some studies to remain unchanged in such animals (Rossier et al, 1977;Kobayashi etal., 1978;Gibson, Ginsburg, Hart & Kitchen, 1980). However, in a recent study it was shown that removal of the anterior lobe of rat pituitary lowers P-endorphin levels in the hypothalamus and in the periventricular tissue (Przewlocki, Millan, Gramsch, Milan & Herz, 1982).…”