Glucocorticoid sensitivity of vasopressin mRNA levels in the paraventricular nucleus of the rat.

Abstract

Immunocytochemical studies have shown that adrenalectomy produces changes in the content and distribution of [arginine-8]vasopressin (AVP) immunoreactivity in the paraventricular nucleus of the hypothalamus. The purpose of this study was to determine whether manipulation of adrenal hormones affects the levels of AVP mRNA. In situ hybridization assays with highly specific synthetic oligodeoxyribonucleotide probes and immunocytochemistry were used to detect the distribution of AVP mRNA and AVP-immunoreactive perikarya. AVP mRNA is codistributed with AVP immunoreactivity in the posterior magnocellular subdivision of the paraventricular nucleus and its accessory nuclei, the supraoptic nucleus and the suprachiasmatic nucleus. In adrenalectomized rats, the density and distribution of the hybridization signal were increased in the paraventricular nucleus; a 2-fold increase in the area comprising the signal was observed. At the cellular level, silver grains were detected in corticotropin-releasing-factor-immunoreactive neurons throughout the medial parvocellular subdivision of the paraventricular nucleus. No changes were seen in the distribution of AVP mRNA in the supraoptic or suprachiasmatic nuclei. Treatment with dexamethasone prevented the increase in AVP mRNA produced by adrenalectomy. In contrast, adrenalectomy did not alter the hybridization signal obtained with a probe for a-tubulin mRNA. These results suggest, at the cellular level, that adrenalectomy induces a glucocorticoid-sensitive stimulation of AVP mRNA synthesis in the central nervous system. Thus, considerable plasticity in gene expression is retained in the hypothalamus of the adult rat.The discrete anatomical organization of hypothalamic neurosecretory neurons within the paraventricular nucleus (PVN) has established this region as a unique site to study the neurohypophyseal secretory system. [arginine-8]Vasopressin (AVP) and oxytocin are contained within neurons of the PVN and the supraoptic nucleus (SON) (1, 2) and are involved in both autonomic and neurosecretory functions (3, 4). The axons emanating from these perikarya form the hypothalamoneurohypophyseal tracts, which project to the pars nervosa where AVP is released from their terminal endings (5,6). However, AVP has been detected in axon terminals within the external zone of the median eminence (7), suggesting that it may be involved, to some extent, in regulating anterior pituitary functions. Unlike the neurohypophyseal projection, the majority of AVP-immunoreactive axon terminals in the median eminence originate from neurons within the medial parvocellular subdivision of the PVN (8). Biochemical studies have confirmed quantitatively that adrenalectomy increases AVP immunoreactivity (7, 9). After adrenalectomy, corticotropin-releasing factor (CRF) and AVP were reported to be colocalized within neurons in the medial parvocellular region of the PVN (10, 12). This finding is of particular interest because immunocytochemical studies have shown that adrenalectomy produces a dexamethasonesen...

Expression of the vasopressin and oxytocin genes in rats occurs in mutually exclusive sets of hypothalamic neurons

“…This sequence element overlaps partially with an ERE of the oxytocin gene -91 to -72) suggesting that positively and negatively acting protein factors may be involved in the expression of this gene. Similar potential regulatory sequence elements can be found in the Table 1 The putative promoter region of the rat oxytocin gene contains several potential gincocorticoid (GRE)-and estrogen-responsive elements (ERE) upstream of the transcription start site promoter region of the vasopressin gene (Mohr, E., unpublished) which agrees with the finding that upregulation of one gene concomitantly affects expression of the other [1][2][3][4][5][6][7][8].…”

“…Conversely the two genes appear to be downregulated when rats are exposed to excess of serum vasopressin [2]. Another regulatory mechanism has been observed in certain cell types of the hypothalamo-pituitary axis where expression of the vasopressin gene is negatively controlled by steroids [3][4][5][6]. Upregulation of the oxytocin gene has been observed in female rats during pregnancy and lactation [7,8] and in analogy to the Correspondence address: D. Richter, Institut fiir Zeilbiochemie und klinisch¢ Neurobiologie, Universit~its-Krankenhaus Eppendorf, Martinistr.…”

Mineralocorticoid and glucocorticoid receptors in the brain. Implications for ion permeability and transmitter systems

“…The change in AVP synthesis was reversible by pretreatment with dexamethasone or corticosterone (Silverman et al, 1981;Davis et al, 1986;Swanson and Simmonds, 1989;Imaki et al, 1991). The effect of stressful stimuli on the synthesis of CRH and AVP in the PVN does not parallel the findings with high levels of exogenously applied corticosteroids.…”

“…Following ADX, CRH synthesizing parvocellular neurons start to produce AVP (Silverman et al, 1981;Tramu et al, 1983;Kiss et al, 1984;Sawchenko et al, 1984;Davis et al, 1986;Swanson and Simmonds, 1989;Imaki et al, 1991). The change in AVP synthesis was reversible by pretreatment with dexamethasone or corticosterone (Silverman et al, 1981;Davis et al, 1986;Swanson and Simmonds, 1989;Imaki et al, 1991).…”

Hypersecretion of corticotrophin-releasing hormone and arginine vasopressin in hypothyroid male rats as estimated with push-pull perfusion

“…Adrenalectomy markedly increases the levels of CRH and AVP immunoreactivity (Antoni et al 1983, Paull & Gibbs 1983, Kiss et al 1984, and the amount of mRNA transcripts of CRH and AVP gene (Wolfson et al 1985, Antoni 1986, Davis et al 1986 in the neurons of the PVN which contains glucocorticoid receptors in rats (Reul & De Kloet 1985). It has also been reported that adrenalectomy increases the concentration of CRH and AVP in hypophysial portal blood (Oliver et al 1983, Kooy et al 1990) and the median eminence (Suda et al 1983, Holmes et al 1986).…”