Adrenalectomy and Experimental Hypercorticalism Modulate the Basal, Corticotropin-Releasing-Hormone- and Arginine-Vasopressin-Stimulated Release of Hypothalamic Beta-Endorphin

Abstract

Recent in vitro studies have shown that the release of hypothalamic β-endorphin (β-END), like that of adenohypo-physial origin, is enhanced by both corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP). However, whereas AVP merely synergizes with CRH in the pituitary, it seems to be essential for the release of hypothalamic β-END by CRH. The present paper reports on the effects of long-term adrenalectomy (ADX) and subsequent replacement with supraphysiological doses of corticosterone (compound B, CB) upon the in vitro basal and CRH- and AVP-stimulated release of β-END from the rat hypothalamus. Basal release of β-END was significantly elevated by ADX, and returned to control levels following CB overdosage. Both ADX and CB replacement significantly reduced the stimulatory effect of CRH (10^–8 M) upon β-END release. ADX caused no significant change in the AVP (10^–6 M)-induced release of β-END. However, the AVP-stimulated release of β-END was completely abolished in ADX rats treated with a high dose of CB. The hypothalamic content of β-END was also measured following ADX and subsequent CB treatment. Compared with control tissues, those from ADX animals had significantly greater contents of β-END; the hypothalami from rats with experimentally induced hypercorticalism had markedly reduced concentrations of the opioid peptide. Measurements of basal release and content of AVP in the hypothalamus following long-term ADX and CB treatment revealed that AVP neuronal activity is also subject to manipulations of the glucocorticoid hormone environment. There was a tendency for hypothalamic levels of AVP to decrease and increase in ADX rats and CB-treated ADX rats, respectively. On the other hand, in the in vitro study, basal release of AVP was significantly increased and decreased in ADX and ADX/CB-supplemented rats, respectively. We conclude that hypothalamic β-END synthesis and basal release, as well as the efficacy of two of the endogenous secretagogues of β-END release, are determined by a fine balance in the levels of circulating glucocorticoids.

Inherent glucocorticoid response potential of isolated hypothalamic neuroendocrine neurons

“…The results from studies in which PVN cells were exposed to DEX, and subsequently deprived of the steroid, were concordant with expectations based on earlier in vivo and in vitro reports (4,5,35,46,47): DEX exposure produced a significant suppression of CRH and AVP secretion, whereas its withdrawal produced a 'rebound' response in the secretion of AVP and restored CRH secretion to basal levels. The results from studies in which PVN cells were exposed to DEX, and subsequently deprived of the steroid, were concordant with expectations based on earlier in vivo and in vitro reports (4,5,35,46,47): DEX exposure produced a significant suppression of CRH and AVP secretion, whereas its withdrawal produced a 'rebound' response in the secretion of AVP and restored CRH secretion to basal levels.…”

“…Experiments were also performed on cultures excluding the ARC, the major b-END-producing site in the brain. The results from studies in which PVN cells were exposed to DEX, and subsequently deprived of the steroid, were concordant with expectations based on earlier in vivo and in vitro reports (4,5,35,46,47): DEX exposure produced a significant suppression of CRH and AVP secretion, whereas its withdrawal produced a 'rebound' response in the secretion of AVP and restored CRH secretion to basal levels. Since b-END may not represent the sole opioid responsible for the observed DEX-stimulated secretion of CRH (PVN neurons also secrete two other opioid peptides, dynorphin and enkephalin, and the receptors for these peptides are also NAL sensitive; see ref 7), we also incubated these PVN cultures with DEX in the presence of NAL.…”

Chronic Daily Ethanol and Withdrawal: 3. Forebrain Pro-Opiomelanocortin Gene Expression and Implications for Dependence, Relapse, and Deprivation Effect

“…Although removal of glucocorticoids by adrenalectomy has been reported not to alter forebrain POMC mRNA concentrations (Scanlon et al, 1992b), there is also evidence that decreased circulating glucocorticoids can increase, and increased glucocorticoids can decrease, forebrain opiomelanocortinergic activity (Almeida et al, 1992;Beaulieu et al, 1988;Patchev et al, 1991). Although removal of glucocorticoids by adrenalectomy has been reported not to alter forebrain POMC mRNA concentrations (Scanlon et al, 1992b), there is also evidence that decreased circulating glucocorticoids can increase, and increased glucocorticoids can decrease, forebrain opiomelanocortinergic activity (Almeida et al, 1992;Beaulieu et al, 1988;Patchev et al, 1991).…”

Effects of Thyroidectomy or Thiouracil Treatment on Copulatory Behavior in Adult Male Rats.

“…Considering the present data and previous observations at our laboratory, we propose that increased levels of CRH from the hypothalamus suppress copulatory behavior in hypothyroid adult male rats. CRH has been also known to increase the β-endorphin release [16] and CRH neurons have a direct synaptic connection to the GnRH neuron within MPOA [13]. β-endorphin and GnRH also may be involved in the process of suppressed copulatory behavior in hypothyroid male rats.…”