Research / Clinical
Summary
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Diseases/Research Topics
Cancer, Control of Differentiation and Development, Development Hormones, Differentiation, Endocrinology, Genetics, Gonadotropin, Hypothalamus, Mouse, Mouse Cancer Genetics, Neuroendocrinology, Pituitary, Reproduction, Steroid Hormones
Leadership Roles:
Leader, Transgenic Core Facility; Vice-Chair for Research in the Department of Reproductive Medicine
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, fertility, and secondary sex characteristics.
Dr. Mellon studies 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 chip analysis.
Using targeted oncogenesis in transgenic mice, Dr. Mellon created a variety of cultured cell models for pituitary endocrine cells and hypothalamic neurons. These models created entirely new directions for molecular research in reproductive neuroendocrinology. A series of pituitary cell lines representing sequential stages in differentiation in pituitary endocrine cell lineages has allowed significant illumination of the control 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.
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