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The brain controls the body's physiology through neurohormones secreted from hypothalamic neurons. In particular, reproduction is regulated by gonadotropin-releasing hormone (GnRH). GnRH is produced in ~800 specialized neurons in the hypothalamus. It controls release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the pituitary. These hormones, in turn, control fertility, gametogenesis, synthesis of gonadal steroids, puberty, menopause, and menstrual cycles. We study the regulation of these hormone genes at the molecular level by steroid and peptide hormones, neurotransmitters, obesity, metabolic state, and throughout development. Using a variety of clonal cell culture models we created for pituitary endocrine cells and hypothalamic neurons in vitro, and analysis in transgenic and knock-out mice in vivo, we investigate the transcriptional regulatory proteins that control development, cellular identity, gene expression, and hormonal response, the pulsatile secretion and circadian rhythms involved in controlling reproductive rhythms, and the hormonal, growth factor, paracrine, autocrine, and endocrine mechanisms regulating these neurons and pituitary cells and thus reproductive function. For example, a series of pituitary cell lines representing sequential stages in differentiation in pituitary endocrine cell lineages has allowed us to significantly illuminate the control of hormone gene expression, synthesis and secretion, as well as pituitary cell fate determination in development. The creation of immortal hypothalamic GnRH neurons has facilitated rapid advances in understanding the roles of neurotransmitters and transcriptional regulators in hypothalamic function. These cells recapitulate the pulsatile release of the GnRH neuropeptide found in the intact hypothalamus, allowing us to determine that this ultradian rhythm is dependent upon circadian rhythm and that cell-cell communication is required for synchrony of the pulsatile rhythm. Thus, a multi-disciplinary approach allows us to investigate and understand the molecular and developmental mechanisms by which the brain governs reproductive function in mammals.

Keywords: Neurobiology, Genetics, Physiology, Endocrinology, Development, Cancer Biology, Hormones, Reproduction, Transgenic Mice, Knock-out Mice, Neuroscience, Hypothalamus, Neuropeptides, Circadian Rhythm, Differentiation

Track(s):
Genetics


BMS Focus Areas:
Neurobiology
Developmental Biology


Endocrinology