Estrogens and Neuroendocrine Hypothalamic-pituitary-adrenal axis function

ALEJANDRO F. DE NICOLA; FLAVIA E. SARAVIA; JUAN BEAUQUIS; LUCIANA PIETRANERA; MONICA G. FERRINI

Pituitary Today: Molecular, Physiological and Clinical Aspects

Karger

Año: 2006; p. 1 - 1

Estrogens control reproductive and non-reproductive events in the brain, and also play a role in the function of the HPA axis. Concerning the last aspect, structures implicated in HPA axis control such as the hippocampus, hypothalamus and the anterior pituitary, are targets of estrogens. Our studies were focused in aging rodents, which presented a marked hyperfunction of the HPA axis. We confirmed that old animals show abnormalities in the response to stress, altered feedback mechanism and low expression of hippocampal 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 the forebrain cholinergic system, which is a known target of estrogens. We found that in old animals, estrogens restored to normal the deficient ChAT immunoreactivity and GAP43 mRNA of the forebrain cholinergic nuclei projecting to the hippocampus. We also studied the estrogen effects on cell proliferation in the dentate gyrus of aging animals. The latter may be an additional control mechanism of the HPA axis, because newborn cells in the subgranular zone of the dentate gyrus differentiate, send projections to the pyramidal cells and integrate into the hippocampal circuitry. It is possible that in aging animals, estrogens modulated the neuroendocrine hippocampus by increasing cell proliferation in the dentate gyrus, and also by attenuation of several markers of aging, such as astrocytosis, high lipofucsine content and neuronal loss in the hilus of the dentate gyrus. In aging animals, hippocampal function and the steroid negative feedback may be reestablished by estrogens, stabilizing the function of the HPA axis. Thus, estrogen regulation of the HPA axis remains an exciting area of research to further understand disbalances affecting the aging hippocampus.