Hormonal regulation of clonal, immortalized hypothalamic neurons expressing neuropeptides involved in reproduction and feeding.

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.