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Hormonal Regulation of Clonal, Immortalized Hypothalamic Neurons Expressing Neuropeptides Involved in Reproduction and Feeding

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Abstract

The hypothalamus has been particularly difficult to study at the molecular level because of the inherent cellular heterogeneity and complexity of neuronal circuits within. We have generated a large number of immortalized, clonal cell lines through retroviral gene transfer of the oncogene SV40 T-Ag into primary murine hypothalamic neuronal cell cultures. A number of these neuronal cell lines express neuropeptides linked to the control of feeding behavior and reproduction, including neuropeptide Y (NPY) and neurotensin (NT). We review recent studies on the direct regulation of NPY gene expression by estrogen, and the leptin-mediated control of signal transduction pathways and NT transcription. These studies provide new insights into the direct control of neuropeptide synthesis by hormones and nutrients at a mechanistic level in the individual neuron, not yet possible in the whole brain. Using these novel cell models, we expect to contribute substantially to the understanding of how individual neuronal cell types control overall endocrine function, especially with regard to two of the most well-known roles of distinct peptidergic neurons; these being the control of reproduction and energy homeostasis.

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Abbreviations

SV40 T-Ag:

simian virus large T antigen

GnRH:

gonadotropin-releasing hormone

NPY:

neuropeptide Y

NT:

neurotensin

AgRP:

agouti-related peptide

MCH:

melanin-concentrating hormone

GHRH:

growth hormone-releasing hormone

POMC:

proopiomelanocortin

CNS:

central nervous system

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Acknowledgements

Thanks to the members of the Belsham Lab, past and present, for the contributions presented herein, particularly Fang Cai, Hong Cui, and Danny Titolo. This work was supported by grants from the Canadian Institutes for Health Research, Natural Sciences and Engineering Research Council of Canada, Canada Foundation for Innovation, and a Premier’s Research Excellence Award. DDB holds a Canada Research Chair in Neuroendocrinology.

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  1. Departments of Physiology, Obstetrics and Gynecology, and Medicine, University of Toronto, Medical Sciences Building 3247A, 1 King’s College Circle, Toronto, ON, M5S 1A8, Canada

    Denise D. Belsham

  2. Division of Cellular and Molecular Biology, Toronto General Hospital Research Institute, University Health Network, Toronto, ON, M5S 1A8, Canada

    Denise D. Belsham

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Correspondence to Denise D. Belsham.

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Belsham, D.D. Hormonal Regulation of Clonal, Immortalized Hypothalamic Neurons Expressing Neuropeptides Involved in Reproduction and Feeding. Mol Neurobiol 35, 182–194 (2007). https://doi.org/10.1007/s12035-007-0010-5

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  • DOI: https://doi.org/10.1007/s12035-007-0010-5

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