Neuroendocrine Control of the Stress Response

Aguilera, G.

Abstract

Research has focused on the mechanism of regulation of hypothalamic and pituitary function during stress. The studies have shown that the level of response of the pituitary corticotroph is determined by differential regulation of the hypothalamic regulators corticotropin releasing hormone (CRH) and vasopressin (VP) and the sensitivity of the glucocorticoid feedback. While the inhibition of the HPA axis during osmotic is associated with stimulation of VP secretion by magnocellular neurons of the paraventricular (PVN) and supraoptic nuclei of the hypothalamus, physical-psychological stress paradigms associated with corticotroph hyperresponsiveness show activation of CRH and CRH/VP parvicellular neurons in the PVN. Binding studies using [3H]VP and anterior pituitary membranes from rats under osmotic stress (water deprivation and 2% saline intake) or physical-psychological stress (immobilization or i.p. hypertonic saline injection) showed a good correlation between changes in pituitary VP receptors and corticotroph responsiveness. Northern blot analysis of VP receptor mRNA in pituitaries from chronically stressed rats revealed changes in mRNA levels parallel to those in VP binding. In contrast to the findings in chronic stress, continuous exposure of the pituitary to increased levels of VP by surgical shunting of magnocellular VP to the hypophyseal portal circulation caused corticotroph desensitization and pituitary VP receptor downregulation. These data suggest that regulation of VP receptor number plays a critical role in the regulation of corticotroph responsiveness during chronic stress. Studies on the expression of CRH receptors in the brain revealed that while CRH binding and CRH receptor mRNA are undetectable in the PVN under basal conditions, they markedly increase during stress with expression in parvicellular cells after physical psychological stress and in magnocellular cells after osmotic stimulation. These data suggest an autoregulatory role for CRH in the control of PVN function.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
• Type: Intramural Research (Z01)
• Project #: 1Z01HD000631-05
• Application #: 3756664
• Support Year: 5
• Fiscal Year: 1994

Institution

• Name: Eunice Kennedy Shriver National Institute of Child Health & Human Development
• Country: United States

Publications

Liu, Ying; Smith, Lorna I; Huang, Victoria et al. (2013) Transcriptional regulation of episodic glucocorticoid secretion. Mol Cell Endocrinol 371:62-70

Stroth, N; Liu, Y; Aguilera, G et al. (2011) Pituitary adenylate cyclase-activating polypeptide controls stimulus-transcription coupling in the hypothalamic-pituitary-adrenal axis to mediate sustained hormone secretion during stress. J Neuroendocrinol 23:944-55

Chen, J; Aguilera, G (2010) Vasopressin protects hippocampal neurones in culture against nutrient deprivation or glutamate-induced apoptosis. J Neuroendocrinol 22:1072-81

Yang, Shutong; Liu, Aiyi; Weidenhammer, Adam et al. (2009) The role of mPer2 clock gene in glucocorticoid and feeding rhythms. Endocrinology 150:2153-60

Blume, Annegret; Torner, Luz; Liu, Ying et al. (2009) Prolactin activates mitogen-activated protein kinase signaling and corticotropin releasing hormone transcription in rat hypothalamic neurons. Endocrinology 150:1841-9

Liu, Ying; Kamitakahara, Anna; Kim, Alice Joohee et al. (2008) Cyclic adenosine 3',5'-monophosphate responsive element binding protein phosphorylation is required but not sufficient for activation of corticotropin-releasing hormone transcription. Endocrinology 149:3512-20

Aguilera, Greti; Subburaju, Sivan; Young, Sharla et al. (2008) The parvocellular vasopressinergic system and responsiveness of the hypothalamic pituitary adrenal axis during chronic stress. Prog Brain Res 170:29-39

Chen, Jun; Volpi, Simona; Aguilera, Greti (2008) Anti-apoptotic actions of vasopressin in H32 neurons involve MAP kinase transactivation and Bad phosphorylation. Exp Neurol 211:529-38

Chen, Jun; Young, Sharla; Subburaju, Sivan et al. (2008) Vasopressin does not mediate hypersensitivity of the hypothalamic pituitary adrenal axis during chronic stress. Ann N Y Acad Sci 1148:349-59

Armando, Ines; Volpi, Simona; Aguilera, Greti et al. (2007) Angiotensin II AT1 receptor blockade prevents the hypothalamic corticotropin-releasing factor response to isolation stress. Brain Res 1142:92-9