Estrogens and neuroendocrine hypothalamic-pituitary-adrenal axis function.

DE NICOLA, ALEJANDRO F; FLAVIA EUGENIA SARAVIA; JUAN BEAUQUIS; PETRANERA, LUCIANA; FERRINI, M

FRONTIERS OF HORMONE RESEARCH.

Año: 2006 vol. 35 p. 157 - 168

0301-3073

Estrogens and Neuroendocrine Hypothalamic-Pituitary-Adrenal Axis Function Alejandro F. De Nicolaa,b, Flavia E. Saraviaa,b, Juan Beauquisa, Luciana Pietraneraa,b, Monica G. Ferrinic aLaboratory of Neuroendocrine Biochemisty, Instituto de Biología y Medicina Experimental, Buenos Aires, bDepartment of Human Biochemistry, Faculty of Medicine, University of Buenos Aires, Buenos Aires, Argentina; cResearch and Education Institute, Harbor-UCLA Medical Center, Urology, Torrance, Calif., USA Abstract The function of the HPA axis is subject to regulation by many factors, which achieve relevance under normal and pathological conditions. In the case of aging, this period of life is associated with disturbances of the HPA axis and signs of hippocampal vulnerability. We examined 20-month-old male rats, in which abnormalities of the HPA axis included altered response to stress, reduced effectiveness of the steroid negative feedback and low expression of hippocampal glucocorticoid receptors (GR). Estrogen treatment of aging rats normalized the response to stress, restored the dexamethasone inhibition of the stress response and increased GR density in defined hippocampal areas. Although estrogens could influence the hippocampus of aging animals directly, their effects could be also mediated by estrogen-sensitive forebrain cholinergic neurons projecting to the hippocampus. Additionally, estrogens normalized the deficient granule cell proliferation that aging mice present in the dentate gyrus, and attenuated several markers of hippocampal aging, such as astrocytosis, high lipofucsin content and neuronal loss in the hilus of the dentate gyrus. These effects may be important for the regulation of the HPA axis, in the context that hippocampal function as a whole was normalized by estrogen action. Therefore, estrogens are powerful neuroprotectants in cases of hippocampal dysfunction, and as part of this effect, they contribute to stabilize the function of the HPA axis.