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Research Topics
Neuroendocrinology of Stress
The goal of the laboratory is to understand the neuroendocrine mechanisms underlying the stress response, with emphasis on the regulation of the hypothalamic pituitary adrenal (HPA) axis. Not only during early development but also during adult life, the ability of the organism to adapt to acute and chronic stress situations is determined by genetic constitution and life experiences. The organism’s degree of adaptability may lead to long-term consequences for the responsiveness of the HPA axis, with altered expression of hypothalamic corticotrophin releasing hormone (CRH) and circulating levels of glucocorticoids—hormones implicated in the pathogenesis of several psychiatric and metabolic disorders. Our laboratory studies the mechanisms of positive and negative regulation of expression of the hypothalamic hormones CRH and vasopressin (VP) and the proteins mediating adrenal steroidogenesis under various physiological situations as well as the impact of stress on HPA axis regulation. The influence of life experiences, especially during early development, on neuroendocrine regulation and the expression of genes involved in the stress response are important aspects of our research program. Elucidation of the mechanisms regulating the production of stress hormones and the effects of life experiences on the stress response is critical for understanding the mechanisms leading to HPA axis dysregulation and for developing diagnostic, preventive, and therapeutic tools for stress-related disorders.
Biography
Dr. Greti Aguilera received an M.D. degree from the University of Chile in 1968. She trained in Clinical Endocrinology, Department of Medicine, University of Chile, and in basic research on steroid biochemistry in the Department of Physiology and Biophysics. In 1975 she joined Dr. Kevin Catt's laboratory at NICHD as an International Fogarty Fellow, in 1977 she was appointed as Visiting Scientist, and then as a Senior Researcher in 1984. Since 1989, she has served as Chief of the Section of Endocrine Physiology within the Program on Developmental Endocrinology and Genetics in NICHD. Research contributions include identification of factors responsible for regulation of adrenal glomerulosa responsiveness to angiotensin II; characterization of the relative role of corticotropin releasing hormone and vasopressin on the HPA axis adaptation during stress; characterization of the properties, signaling-transduction, and regulation of the receptors for these peptide hormones, and the identification of novel mechanisms for the transcriptional regulation of CRH. Current work in Dr. Aguilera's laboratory focuses on the molecular mechanisms of positive and negative regulation of CRH transcription responsible for the rapid but transient responses to stress, the consequences of early life experiences and circadian and ultradian rhythms of glucocorticoid secretion on gene transcription, and the mechanisms determining pulsatile glucocorticoid secretion by the adrenal.
Selected Publications
Liu Y, Knobloch HS, Grinevich V, Aguilera G. Stress induces parallel changes in corticotrophin-releasing hormone (CRH) Transcription and nuclear translocation of transducer of regulated cAMP response element-binding activity 2 in hypothalamic CRH neurones. J Neuroendocrinol. 2011;23(3):216-23.
Spiga F, Waite EJ, Liu Y, Kershaw YM, Aguilera G, Lightman SL. ACTH-dependent ultradian rhythm of corticosterone secretion. Endocrinology. 2011;152(4):1448-57.
Watts AG, Sanchez-Watts G, Liu Y, Aguilera G. The distribution of messenger RNAs encoding the three isoforms of the transducer of regulated cAMP responsive element binding protein activity in the rat forebrain. J Neuroendocrinol. 2011;23(8):754-66.
Spiga F, Liu Y, Aguilera G, Lightman SL. Temporal effect of adrenocorticotrophic hormone on adrenal glucocorticoid steroidogenesis: involvement of the transducer of regulated cyclic AMP-response element-binding protein activity. J Neuroendocrinol. 2011;23(2):136-42.
Stroth N, Liu Y, Aguilera G, Eiden LE. Pituitary adenylate cyclase-activating polypeptide controls stimulus-transcription coupling in the hypothalamic-pituitary-adrenal axis to mediate sustained hormone secretion during stress. J Neuroendocrinol. 2011;23(10):944-55.