Elsevier

Neuroscience

Volume 99, Issue 4, 23 August 2000, Pages 751-760
Neuroscience

Insulin-like growth factor I receptors and estrogen receptors colocalize in female rat brain

https://doi.org/10.1016/S0306-4522(00)00228-1Get rights and content

Abstract

Several findings indicate that there is a close interaction between estrogen and insulin-like growth factor I in different brain regions. In adult brain, both estrogen and insulin-like growth factor I have co-ordinated effects in the regulation of neuroendocrine events, synaptic plasticity and neural response to injury. In this study we have qualitatively assessed whether estrogen receptors and insulin-like growth factor I receptor are colocalized in the same cells in the preoptic area, hypothalamus, hippocampus, cerebral cortex and cerebellum of female rat brain using confocal microscopy. Immunoreactivity for estrogen receptors α and β was colocalized with immunoreactivity for insulin-like growth factor I receptor in many neurons from the preoptic area, hypothalamus, hippocampus and cerebral cortex. Furthermore, estrogen receptor β and insulin-like growth factor I receptor immunoreactivities were colocalized in the Purkinje cells of the cerebellum. Colocalization of estrogen receptor β and insulin-like growth factor I receptor was also detected in cells with the morphology of astrocytes in all regions assessed. The co-expression of estrogen receptors and insulin-like growth factor I receptor in the same neurons may allow a cross-coupling of their signaling pathways. Furthermore, the colocalization of immunoreactivity for estrogen receptor β and insulin-like growth factor I receptor in glial cells suggests that glia may also play a role in the interactions of insulin-like growth factor I and estrogen in the rat brain.

In conclusion, the co-expression of estrogen receptors and insulin-like growth factor I receptors in the same neural cells suggests that the co-ordinated actions of estrogen and insulin-like growth factor I in the brain may be integrated at the cellular level.

Section snippets

Animals

Female Wistar rats from our in-house breeding colony were kept in a 12:12 h light/dark cycle and studied when they were 40 days old. Animals received food and water ad libitum. They were handled according to European Union (86/609/EEC) guidelines on animal care. Special care was taken to minimize animal suffering and to reduce the number of animals used.

Inmunohistochemistry

All animals were killed by perfusion, under pentobarbital anesthesia, through the left cardiac ventricle when they were 40 days old. Animals

Results

ERα immunoreactivity had a neuronal localization and was observed exclusively in cell nuclei. Cell nuclei immunoreactive for ERα were observed in different brain regions, including the preoptic area, hypothalamus, hippocampus and cerebral cortex (Fig. 2). ERβ immunoreactivity was observed in neuronal cell nuclei and in the neuronal cytoplasm (Fig. 3, Fig. 4). Neurons in some areas such as the supraoptic nucleus (Fig. 3d) or the paraventricular nucleus (magnocellular neurons) showed an almost

Discussion

Our findings indicate that ERs colocalize with IGF-IR in different neuronal subpopulations in the female rat brain. In agreement with previous studies, we have found IGF-I receptor immunoreactivity in neurons and glial cells in the preoptic area, hypothalamus, hippocampus, cerebral cortex and cerebellum.1., 14., 32., 37., 51., 55., 96. The localization of ERα immunoreactivity in our study is also in agreement with previous reports showing that ERα has a neuronal and nuclear localization and it

Acknowledgements

We would like to thank Concha Bailon for excellent technical assistance in confocal microscopy, and Dr Sebastián Pons and the Instituto Cajal, CSIC antibodies service for their production of the IGF-IR mouse polyclonal antibody. This work was sponsored by Comunidad de Madrid (grant no. 08.5/0009/97), Dirección General de Enseñanza Superior e Investigación Cientı́fica (grant no. PM98-0110), and the Fundación Endocrinologı́a y Nutrición. G.P.C.-G. is a fellow from Colciencias,

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