Role of the Paraventricular Nucleus Microenvironment In Stress Integration* (original) (raw)
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European Journal of Neuroscience, 2002
Magnocellular vasopressinergic and oxytocinergic neurons of the hypothalamic supraoptic (SON) and paraventricular nuclei comprise the hypothalamic±neurohypophysial system, which is crucially involved in the regulation of body¯uid and electrolyte homeostasis. However, still controversial is to what extent the same system in¯uences the secretion of adrenocorticotropic hormone (ACTH) from the adenohypophysis. Therefore, we selectively stimulated magnocellular neurons of the SON of conscious male Wistar rats via retrodialysis. As expected, dialysis of the SON with hypertonic medium increased both the release of vasopressin within the SON and the secretion of vasopressin and oxytocin into the systemic blood circulation. This activation of the hypothalamic±neurohypophysial system was accompanied by a ®vefold increase in plasma ACTH concentration. This effect was observed only if the tip of the microdialysis probe was within the SON. Intravenous infusion of the vasopressin V1 receptor antagonist d(CH 2 ) 5 Tyr(Me)AVP signi®cantly attenuated the effects of local osmotic stimulation of the SON on ACTH secretion. In contrast, administration of the same antagonist directly into the SON signi®cantly enhanced the osmotically stimulated secretion of ACTH and corticosterone, primarily by delaying the restoration of the hormone secretion to prestimulation levels. We conclude from these ®ndings that vasopressin from the hypothalamic±neurohypophysial system participates in the regulation of the hormonal stress response in a counterbalanced manner at the level of the SON and the adenohypophysis.
Annals of the New York Academy of Sciences, 1977
A physiologic role for vasopressin in the regulation of ACTH secretion has been debated for more than 20 years.'-'< In the 1950s it was shown that a deficient adrenal response to stress in rats with experimental diabetes insipidus could be corrected by the administration of posterior pituitary extracts containing vasopre~sin.~, s However, the exogenous systemic dose of vasopressin required to release ACTH was a 1000-fold greater than the amount that produced antidiuresis.6 In addition, endogenous release of the hormone stimulated by intracarotid hypertonic saline was not associated with activation of the adrenal cortex.6 Unless vasopressin was secreted into the hypophyseal portal system in the zona externa of the median eminence in very high concentrations by a separate pathway from the one to the posterior pituitary, it did not seem likely that the hormone had any normal role in the regulation of ACTH.4j
The Journal of Neuroscience, 1984
Experiments were designed to identify hemodynamically sensitive neurons in the mediodorsal hypothalamus and to determine if they were also sensitive to electrical stimulation of areas in the dorsal rostra1 pons that were implicated previously in the control of adrenocorticotropin (ACTH) release. Cats were anesthetized with chloralose and urethane, immobilized with gallamine, and artificially respired. Hemodynamic stimuli included constriction (CC) of the supradiaphragmatic inferior vena cava to reduce venous return and sinusoidal volume pulsation (RA) of the right atrium (1 ml peak at 1 Hz). Previously, CC was shown to facilitate and RA was shown to inhibit ACTH release. Electrical stimulation in the pons consisted of single shocks (500 PA DC, 0.05 msec, negative-to-tip) delivered on each of an array of three or four bipolar co-axial electrodes in the pons. Twenty-three neurons were tested with only RA. Of these, two were inhibited, two were facilitated, and 19 did not respond. Thirty-two neurons were tested with CC. Of these, nine were inhibited, nine were facilitated, and 14 did not respond. Seventeen neurons that responded either to RA or to CC were tested with stimulation in the pons. Of these, three were orthodromicallv activated and two were inhibited from a total of eight pontine sites. Six of the eight sites were within 300 pm of an area shown previously to contain neurons that responded to CC. Of 31 additional sites that were stimulated, but at which stimulation did not drive neurons that responded to hemodynamic stimuli, 26 were located more than 300 pm from this area (p < 0.01, x2 test). The data suggest that some hypothalamic neurons involved in the hemodynamic control of ACTH release receive a projection from or through the dorsal raphe nucleus medially, and the ventral locus ceruleus, locus subceruleus, and underlying reticular formation laterally. However, other neurons may receive projections that bypass these regions. ' We thank Kathleen T. Cruz for preparing the manuscript.
Journal of Neuroendocrinology, 2012
Corticotrophin-releasing hormone (CRH) neuroendocrine neurones in the paraventricular nucleus of the hypothalamus (PVH) drive adrenocorticotrophic hormone (ACTH) and thereby glucocorticoid release from pituitary corticotrophs and the adrenal cortex, respectively. Glucocorticoids suppress the ability of neuroendocrine corticotrophin-releasing hormone (CRH) neurones to synthesise and release ACTH secretogogues. Despite the importance of glucocorticoids as regulatory signals to CRH neurones in the extended time domain, how and where they act in this capacity is still not fully understood. Ascending catecholamine projections encode important cardiovascular, metabolic and other visceral information to the rat PVH and surrounding hypothalamus. These afferents have previously been implicated as targets for glucocorticoid action, including a role in the feedback regulation of PVH neuroendocrine neurones. To determine the contribution of these neurones to the long-term actions of corticosterone on CRH and vasopressin (AVP) gene expression in the PVH, we used an immunocytotoxin (a conjugate of the cytotoxin saporin and an antibody against dopamine-b-hydroxylase) that specifically ablates adrenergic and noradrenergic neurones. Lesions were administered to intact animals and to adrenalectomised animals with either no corticosterone or corticosterone replacement that provided levels above those required to normalise Crh expression. The ability of elevated levels of corticosterone to suppress Crh expression was abolished in animals lacking catecholaminergic innervation of the PVH. No effect was seen in the absence of corticosterone or in animals with intact adrenals. Furthermore, Avp expression, which is increased in CRH neurones following adrenalectomy, was suppressed in adrenalectomised catecholaminergic-lesioned animals. Interactions between corticosterone and catecholaminergic projections to the hypothalamus therefore make significant contributions to the regulation of Crh and Avp expression. However, the importance of catecholamine inputs is only apparent when circulating corticosterone concentrations are maintained either below or above those required to maintain the activity of the hypothalamic-pituitary-adrenal axis that is seen in intact animals.
Journal of Neuroendocrinology, 1996
The role of afferent innervation to the hypothalamic paraventricular nucleus (PVN) on CRH mRNA and CRH receptor mRNA levels was studied in control and stressed rats. Groups of rats were subjected to unilateral transection of the stria terminalis (ST), the medial forebrain bundle at the rostra1 hypothalamic level (RMFB), or the lower brainstem through the medulla oblongata between the obex and the locus coeruleus (CBs). Twelve days after surgery, each group of rats was further divided into controls (basal conditions) and stressed (1 h immobilization), before collecting brains for mRNA analysis by in situ hybridization histochemistry. While ST and RMFB cuts had no effect on basal CRH mRNA levels in the PVN, CBs cut decreased CRH mRNA in the PVN ipsilaterally to the knife cut but it was without effect on the contralateral side (-40% and -37% vs contralateral and sham-operated, respectively, P<O.Ol). Acute stress (rats were killed 3 h after immobilization) increased CRH mRNA levels by about 30% bilaterally, an effect which was unchanged by any of the three hemisections.
Stress-the International Journal on The Biology of Stress, 2009
Although previous studies have examined the extent to which adrenocorticotropic hormone (ACTH) secretion depends on endogenous glucocorticoid levels, few have examined the parallel glucocorticoid dependency of gene expression within the corticotropin releasing hormone (CRH) neuron containing subregion of the hypothalamic paraventricular nucleus (PVN). This study examined resting and stress-induced expression of three immediate early genes (c-fos, zif268, and NGFI-B mRNAs) and two phenotypic restricted immediate early genes that code for ACTH secretagogues (CRH and arginine vasopressin [AVP] hnRNAs) in the PVN of adrenalectomized (ADX) rats given either 0.9% saline to drink for 5 days or saline with corticosterone (CORT; 25 µg/ ml). CORT-containing saline was replaced with saline 18 h before testing to ensure clearance of CORT at the time of testing. Dependent measures were examined 0, 15, 30, 60, or 120 min after 30 min restraint. Compared to sham surgery, ADX produced a large upregulation of basal ACTH secretion but only a trend for an increase in basal PVN CRH and parvocellular (mp) PVN AVP hnRNA expression, and a marked augmentation of restraint-induced ACTH secretion and the expression of all five genes examined. CORT containing saline partially normalized basal and restraint-induced ACTH secretion and restraint-induced AVP hnRNA, c-fos mRNA, and zif268 mRNA in the PVN in ADX rats. In contrast, expression patterns of restraint-induced PVN CRH hnRNA and NGFI-B mRNA were not different between ADX rats with or without CORT replacement. Given that there was no circulating CORT present at the time of restraint challenge in either group of ADX rats, the differential impact of CORT replacement on restraint-induced PVN gene expression must reflect differential dependency of the expression of these genes in the PVN on the prior presence of CORT.