Regulation of estradiol synthesis in the hippocampus
The steroid hormone estradiol is not only produced in the reproductive tract but also in the brain. Aromatase, the enzyme that converts testosterone into estradiol, has been detected in various brain regions in many species, including human, mouse and rat. Our laboratory is focused on the role of aromatase and estradiol in the hippocampus, a brain region that is crucial for learning and memory. Previously, we demonstrated that hippocampus-derived estradiol is an important regulator of synapse formation and maintenance. Furthermore, the locally produced estradiol influences neurogenesis in the hippocampus. However, the regulation of aromatase transcription and activity in the hippocampus is barely understood. Using molecular approaches we aim at identifying the underlying mechanisms of the regulation of aromatase transcription in the hippocampus. In a recent paper, we demonstrated that Gonadotropin Releasing Hormone (GnRH) regulates hippocampal estradiol synthesis in an in-vitro model. These findings suggest, that factors that are known to regulate the gonadal aromatase expression, like GnRH, are also involved in the aromatase regulation in the hippocampus. Another factor that might play a role in hippocampal aromatase transcription is SF-1. SF-1 is a transcription factor that is known to induce aromatase expression in the ovary and that is also expressed in the rat hippocampus. Using a brain-specific SF-1 knock out mouse we are going to elucidate its role in hippocampal aromatase expression.
The role of hippocampal aromatase in Alzheimer′s Disease
Recent studies using aromatase knock-out mice, showed that the lack of local production of estradiol results in an early development of symptoms of Alzheimer′s Disease (AD) in AD-model mice that express a mutant form of the amyloid precursor protein (APP). These findings imply that locally produced estradiol might be protective against this disease. Currently, very little is known on whether aromatase expression is altered in AD patients. The Alzheimer′s Disease Center at UT Southwestern provides human material that will allow us to answer this question. Furthermore, we use AD mouse models to investigate the time course of potential changes in aromatase expression in the progression of the disease and as an experimental approach.
RESEARCH INTERESTS
Steroids in the brain
Regulation of hippocampal estradiol synthesis
Effects of estradiol and synaptic plasticity
RECENT PUBLICATIONS
Prange-Kiel J, Jarry H, Schoen M, Kohlmann P, Lohse C, Zhou L, Rune GM, "Gonadotropin-releasing hormone regulates spine density via its regulatory role in hippocampal estradiol synthesis" Journal of Cell Biology, 180/2:417-26, January 2008
von Schassen C, Fester L, Prange-Kiel J, Lohse C, Huber C, Boettner M, Rune GM, "Oestrogen synthesis in the hippocampus: role in axon outgrowth" Journal of Neuroendocrinology, 18/11:847-56, November 2006
Rune GM, Lohse C, Prange-Kiel J, Fester L, Frotscher M., "Synaptic plasticity in the hippocampus: effects of estrogen from the gonads or hippocampus?" Neurochemical Research, 31/2:145-55, February 2006
Fester L, Ribeiro-Gouveia V, Prange-Kiel J, von Schassen C, Bottner M, Jarry H, Rune GM, "Proliferation and apoptosis of hippocampal granule cells require local oestrogen synthesis." Journal of Neurochemistry, 97/4:1136-44, May 2006
Prange-Kiel J, Fester L, Zhou L, Lauke H, Carretero J, Rune GM., "Inhibition of hippocampal estrogen synthesis causes region-specific downregulation of synaptic protein expression in hippocampal neurons." Hippocampus, 16/5:464-71, 2006
SIGNIFICANT PUBLICATIONS
Prange-Kiel J, Kreutzkamm C, Wehrenberg U, Rune GM., "Role of tumor necrosis factor in preovulatory follicles of swine." Biology of reproduction, 65/3:928-35, September 2001
Prange-Kiel J, Jarry H, Schoen M, Kohlmann P, Lohse C, Zhou L, Rune GM., "Gonadotropin-releasing hormone regulates spine density via its regulatory role in hippocampal estrogen synthesis." Journal of Cell Biology, 180/2:417-26, February 2008
Prange-Kiel J, Fester L, Zhou L, Lauke H, Carretero J, Rune GM., "Inhibition of hippocampal estrogen synthesis causes region-specific downregulation of synaptic protein expression in hippocampal neurons." Hippocampus, 16/5:464-71, 2006
Kretz O, Fester L, Wehrenberg U, Zhou L, Brauckmann S, Zhao S, Prange-Kiel J, Naumann T, Jarry H, Frotscher M, Rune GM., "Hippocampal synapses depend on hippocampal estrogen synthesis." Journal of Neuroscience, 24/26:5913-21, June 2004
Prange-Kiel J, Rune GM, Leranth C., "Median raphe mediates estrogenic effects to the hippocampus in female rats." European Journal of Neuroscience, 19/2:309-17, January 2004
Prange-Kiel J, Wehrenberg U, Jarry H, Rune GM., "Para/autocrine regulation of estrogen receptors in hippocampal neurons." Hippocampus, 13/2:226-34, 2003
Prange-Kiel J, Kreutzkamm C, Wehrenberg U, Rune GM., "Role of tumor necrosis factor in preovulatory follicles of swine." Biology of reproduction, 65/3:928-35, September 2001
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