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The brain controls the body’s physiology through neurohormones secreted from the hypothalamus. In particular, reproduction is regulated by the decapeptide gonadotropin-releasing hormone (GnRH). GnRH is produced by as few as 800 specialized neurons in the hypothalamus. Its function is to control release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the pituitary. These hormones in turn control gametogenesis, puberty, menopause, menstrual cycles, and fertility.
We study the regulation of these hormone genes at the molecular level both by hormones and neurotransmitters and throughout development. We use an integrated program of molecular approaches including: 1) Analysis in transgenic and knock-out mice; 2) Generation of novel pituitary and hypothalamic cell lines; 3) Investigation of the transcriptional regulatory proteins that control development, cellular identity, gene expression, and hormonal response; 4) Pulsatile secretion and circadian rhythms; and 5) Genomic approaches including DNA array analysis.
Using targeted oncogenesis in transgenic mice, we have created a variety of cultured cell models for pituitary endocrine cells and hypothalamic neurons. The impact of the development of these models has been enormous, creating entirely new directions for molecular research in reproductive neuroendocrinology. The creation of a series of pituitary cell lines representing sequential stages in development within several of the anterior pituitary endocrine cell lineages has allowed us to significantly illuminate the developmental and hormonal regulation of hormone gene expression, synthesis and secretion. The creation of immortal hypothalamic GnRH neurons has facilitated rapid advances in understanding the roles of neurotransmitters and transcriptional regulators in hypothalamic function. For example, this model allowed the demonstration that the GnRH pulse generator is intrinsic to the GnRH neuron, since secretion is pulsatile in these clonal cells in culture. In addition to Dr. Mellon's own important contributions, researchers around the world are using her cultured cell models to study key issues in neuroendocrinology that were previously unapproachable. The impact of these model systems has produced a revolution in the approaches used to study the neuroendocrinology of reproduction.
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