Vasopressinergic Regulation of the Hypothalamic Pituitary Adrenal Axis and Stress Adaptation

“…leading to the production of intermediate early genes or transcription factors capable to interact with glucocorticoid receptors and to modify their activity at the responsive element in the gene promoter (Diamond et al., 1990; Morgan and Curran, 1991; Webster and Cidlowski, 1999).”

“Glucocorticoids are likely to act at multiple sites, inhibiting VP secretion by direct actions on the parvocellular neuron, and indirectly by modifying the activity of neural pathways to the parvocellular neuron such as GABAergic and glutamatergic afferents (Herman and Cullinan, 1997; Kiss, 1998).”

“Upstream ORFs have been described in yeast and several eukaryotic mRNAs and are recognized to reduce the ability of ribosomes to linearly scan the V1b 50UTR mRNA according to conventional scanning models and therefore to slow translation (Kozak, 1991).”

“…leading to the production of intermediate early genes or transcription factors capable to interact with glucocorticoid receptors and to modify their activity at the responsive element in the gene promoter (Diamond et al., 1990; Morgan and Curran, 1991; Webster and Cidlowski, 1999).”

“In humans and rodents, VP alone is a weak stimulus of ACTH secretion, but through its interaction with CRH it contributes to maintaining corticotroph responsiveness in spite of elevated glucocorticoid levels during chronic stress (Gilles et al., 1982; Antoni, 1993; Aguilera, 1994).”

“Recent studies show that glucocorticoids induce the release of endogenous cannabinoids in the PVN, which can mediate rapid indirect, non-genomic glucocorticoid feedback in the parvocellular neuron (Di et al., 2003).”

“Circulating glucocorticoids exert a negative feedback effect on the expression of CRH and VP in parvocellular PVN neurons (Dallman et al., 1987), but there is evidence of preferential inhibition of VP compared with CRH expression (Ma et al.”

“external zone of the median eminence (Antoni, 1993).”

“Also, VP markedly potentiates the stimulatory effects of corticotropin releasing hormone (CRH) on ACTH secretion (Gilles et al., 1982; DeGoeij et al., 1991; Aguilera, 1994).”

“In addition to receptor synthesis, the number of active VP receptors could be influenced by ligand binding, leading to receptor desensitization and internalization as occurs with other G-protein coupled receptors (Catt et al., 1979; Ferguson and Caron, 1998).”

“Molecular cloning and pharmacological tools have identified three major receptor subtypes encoded by different genes; kidney V2 receptors, which are coupled to the G-protein, Gs, and adenylate cyclase; V1a receptors, present in smooth muscle and liver, coupled to phospholipase C (PLC); and the pituitary V1b receptors…”

“…G-protein, Gs, and adenylate cyclase; V1a receptors, present in smooth muscle and liver, coupled to phospholipase C (PLC); and the pituitary V1b receptors (V1bR or V3), also linked to PLC; (Lolait et al., 1992; Morel et al., 1992; Seibold et al., 1992; Sumimoto et al., 1994; Lolait et al., 1995).”

“The isolation of the V1bR cDNA (Sumimoto et al., 1994; Lolait et al., 1995) and the more recent identification and characterization of genomic clones and 50flanking region have facilitated the understanding of the molecular mechanisms of regulation of the receptor (De Keyser et al.”

“Experiments using adrenalectomized rats and glucocorticoid administration have shown that the parvocellular neuron becomes more sensitive to stress in the absence of glucocorticoids (Makino et al., 1995; Ma and Aguilera, 1999; Kovacs et al., 2000).”

“The isolation of the V1bR cDNA (Sumimoto et al., 1994; Lolait et al., 1995) and the more recent identification and characterization of genomic clones and 50flanking region have facilitated the understanding of the molecular mechanisms of regulation of the receptor (De Keyser et al., 1994; Ventura…”

“Acute stress leads to rapid release of CRH and VP into the pituitary portal circulation from parvocellular neurons of the PVN (Berkenbosh et al., 1989; Plotsky, 1991; Kovacs and Sawchenko, 1996).”

“…to its recognized role in water conservation, the nanapeptide vasopressin (VP) plays a role in stress adaptation acting as a neurotransmitter in the brain (Engelmann et al., 1996) as well as a regulator of pituitary corticotroph function (McCann and Brobeck, 1954; Antoni, 1993; Aguilera, 1994).”

“Acute stress leads to rapid release of CRH and VP into the pituitary portal circulation from parvocellular neurons of the PVN (Berkenbosh et al., 1989; Plotsky, 1991; Kovacs and Sawchenko, 1996).”

“Also, VP markedly potentiates the stimulatory effects of corticotropin releasing hormone (CRH) on ACTH secretion (Gilles et al., 1982; DeGoeij et al., 1991; Aguilera, 1994).”

“There is evidence that upstream peptides encoded by uORFs of the mRNAs of the CRH type 1 receptor, b2-adrenergic and type 1 angiotensin II receptors may also mediate inhibition of translation of the receptor proteins (Parola and Kobilka, 1994; Mori et al., 1996; Xu et al., 2001).”

“can stimulate ACTH secretion under acute conditions (Holmes et al., 1986; Irvine et al., 1989; Aguilera, 1994)”

“In addition to receptor synthesis, the number of active VP receptors could be influenced by ligand binding, leading to receptor desensitization and internalization as occurs with other G-protein coupled receptors (Catt et al., 1979; Ferguson and Caron, 1998).”

“…glucocorticoids exert a negative feedback effect on the expression of CRH and VP in parvocellular PVN neurons (Dallman et al., 1987), but there is evidence of preferential inhibition of VP compared with CRH expression (Ma et al., 1997; Ma and Aguilera, 1999; Kovacs et al., 2000).”

“The actions of VP are mediated by plasma membrane receptors of the guanyl nucleotide binding protein (Gprotein) coupled receptor family (Jard et al., 1987; Peter et al., 1995).”

“…leading to the production of intermediate early genes or transcription factors capable to interact with glucocorticoid receptors and to modify their activity at the responsive element in the gene promoter (Diamond et al., 1990; Morgan and Curran, 1991; Webster and Cidlowski, 1999).”

“…to its recognized role in water conservation, the nanapeptide vasopressin (VP) plays a role in stress adaptation acting as a neurotransmitter in the brain (Engelmann et al., 1996) as well as a regulator of pituitary corticotroph function (McCann and Brobeck, 1954; Antoni, 1993; Aguilera, 1994).”

“A similar lack of correlation between VP binding and receptor mRNA has been observed for the V1a and V2 VP receptors (Terada et al., 1993; Young et al., 1993).”

“The actions of VP are mediated by plasma membrane receptors of the guanyl nucleotide binding protein (Gprotein) coupled receptor family (Jard et al., 1987; Peter et al., 1995).”

“Glucocorticoids are likely to act at multiple sites, inhibiting VP secretion by direct actions on the parvocellular neuron, and indirectly by modifying the activity of neural pathways to the parvocellular neuron such as GABAergic and glutamatergic afferents (Herman and Cullinan, 1997; Kiss, 1998).”

“However, transfection of an expression vector for a GAGA binding protein identified in Drosophila (Benyajati et al., 1997) increases V1bR mRNA in H32 or MCF-7 cells, which express endogenous receptor (Volpi et al.”

“This suggests that VP receptor content is controlled at the translational and posttranslational levels rather than by the levels of V1bR mRNA (Rabadan-Diehl et al., 1995; 1997).”

“This effect of glucocorticoids is in part mediated by increase in the content of the coupling protein Gq in the pituitary (Rabadan-Diehl and Aguilera, 1998) (Fig.”

“The mechanism of the synergism between CRH and VP includes protein kinase C-(PKC) mediated potentiation of CRH-stimulated cAMP production, as well as post-cAMP dependent mechanisms (Bilezikjian et al., 1987; Carvallo and Aguilera, 1989).”

“Corticosterone markedly decreases the elevated basal VP hnRNA levels in parvocellular PVN neurons observed 48 h or 6 days after adrenalectomy (Ma et al., 1997; Ma and Aguilera, 1999).”

“Recent studies show that glucocorticoids induce the release of endogenous cannabinoids in the PVN, which can mediate rapid indirect, non-genomic glucocorticoid feedback in the parvocellular neuron (Di et al., 2003).”

“A similar lack of correlation between VP binding and receptor mRNA has been observed for the V1a and V2 VP receptors (Terada et al., 1993; Young et al., 1993).”

“The mechanism of the synergism between CRH and VP includes protein kinase C-(PKC) mediated potentiation of CRH-stimulated cAMP production, as well as post-cAMP dependent mechanisms (Bilezikjian et al., 1987; Carvallo and Aguilera, 1989).”

“can stimulate ACTH secretion under acute conditions (Holmes et al., 1986; Irvine et al., 1989; Aguilera, 1994)”

“Studies in hypothalamic organotypic cultures containing parvocellular neurons revealed that glucocorticoids inhibit forskolin-stimulated VP hnRNA expression in the presence of tetrodotoxin, which inhibits synaptic transmission (Kuwahara et al., 2003).”

“…ACTH secretion under acute conditions (Holmes et al., 1986; Irvine et al., 1989; Aguilera, 1994) but prolonged activation of magnocellular VP neurons inhibits rather than stimulates the hypothalamic– pituitary–adrenal (HPA) axis (Dohanics et al., 1990; Chowdry et al., 1991; Aguilera, 1994).”

“There is evidence that upstream peptides encoded by uORFs of the mRNAs of the CRH type 1 receptor, b2-adrenergic and type 1 angiotensin II receptors may also mediate inhibition of translation of the receptor proteins (Parola and Kobilka, 1994; Mori et al., 1996; Xu et al., 2001).”

“, 1995) and the more recent identification and characterization of genomic clones and 50flanking region have facilitated the understanding of the molecular mechanisms of regulation of the receptor (De Keyser et al., 1994; Ventura et al., 1999; Rabadan-Diehl et al., 2000; Rene et al., 2000).”

“This suggests that VP receptor content is controlled at the translational and posttranslational levels rather than by the levels of V1bR mRNA (Rabadan-Diehl et al., 1995; 1997).”

“…ACTH secretion under acute conditions (Holmes et al., 1986; Irvine et al., 1989; Aguilera, 1994) but prolonged activation of magnocellular VP neurons inhibits rather than stimulates the hypothalamic– pituitary–adrenal (HPA) axis (Dohanics et al., 1990; Chowdry et al., 1991; Aguilera, 1994).”

“, 2002), suggests that the GAGA repeats are required for initiation of transcription, similar to observations in the type-1 angiotensin receptor and serine protease inhibitor genes (Simar-Blanchet et al., 1998; Wyse et al., 2000).”

“In vitro experiments have shown that VP increases the number of cells responsive to CRH in vitro (Jia et al., 1992), possibly by increasing the number of cells expressing CRH receptors.”

“On the other hand, the VP gene promoter contains an active glucocorticoid response element (GRE; Burke et al., 1997) capable of mediating transcriptional inhibition by glucocorticoids.”

“, 2002), suggests that the GAGA repeats are required for initiation of transcription, similar to observations in the type-1 angiotensin receptor and serine protease inhibitor genes (Simar-Blanchet et al., 1998; Wyse et al., 2000).”

“…et al., 1995) and the more recent identification and characterization of genomic clones and 50flanking region have facilitated the understanding of the molecular mechanisms of regulation of the receptor (De Keyser et al., 1994; Ventura et al., 1999; Rabadan-Diehl et al., 2000; Rene et al., 2000).”

“corresponds to a homo- or heterodimer of proteins of about ,70 kDa (Volpi et al., 2002).”

“of translation of the receptor proteins (Parola and Kobilka, 1994; Mori et al., 1996; Xu et al., 2001).”

“Mutations that inactivate the upstream ORFs in the V1bR mRNA have been shown to increase in vitro translation of a 46 kDa band corresponding to the V1bR (Rabadan-Diehl and Aguilera, 2002), or luciferase activity using reporter gene constructs (Nomura et al., 2001).”

“Vasopressinergic regulation of ACTH secretion depends on the number of V1bRs as well as coupling of the receptor to phospholipase C (PLC) in the pituitary.”

“Recent studies have focused on the translational regulation of the V1bR, and especially on the role of the 50UTR (Nomura et al., 2001; Rabadan-Diehl and Aguilera, 2002; Rabadan-Diehl et al., 2003).”

“As such, VP is part of the hypothalamic-pituitaryadrenal (HPA) axis, a system involved in the neuroendocrine stress response (Herman, 1995; Volpi et al., 2004).”

“Although the role of vasopressin in regulating ACTH secretion in responses to stress is well known (Volpi et al., 2004), current evidence suggests that vasopressin does not regulate basal HPA axis activity.”

“…the role of the Avpr1b in regulating adrenocorticotropin hormone from the anterior pituitary in response to stress, especially chronic, has been extensively studied (for reviews, see (Engelmann et al., 2004; Volpi et al., 2004)) ever since the receptor was first described (Antoni et al., 1984).”