Ursula B. Kaiser, MD
My laboratory studies the neuroendocrine regulation of reproductive function, with a focus on determining the molecular mechanisms by which pulsatile gonadotropin-releasing hormone (GnRH) specifically and differentially regulates luteinizing hormone (LH) and follicle-stimulating hormone (FSH). The frequency and amplitude of pulsatile GnRH release vary temporally and developmentally, and this variation is critical for normal reproductive maturation and function. We are using four approaches to determine how gonadotropes respond to varying frequencies of pulsatile GnRH with differential LH and FSH production. First, we have identified and characterized the roles of transcription factors Sp1, Egr1, and SF-1 in regulating LH gene expression, and of Pitx1 and Smad proteins in regulation of the FSH gene, towards the goal of identifying the unique transcriptional control mechanisms that allow differential responses to distinct patterns of pulsatile GnRH. Second, we have identified signal transduction pathways by which pulsatile GnRH mediates the transcriptional responses of the LH and FSH genes, and have developed evidence supporting a model wherein GnRH receptor (GnRHR) concentrations are critical in dictating these responses. Third, given this important role for GnRHR concentrations, we have studied GnRHR gene regulation. Finally, we have applied our knowledge of the cellular mechanisms of GnRH and gonadotropin regulation to better understand the genetic and molecular defects in patients with idiopathic hypogonadotropic hypogonadism (IHH) and other reproductive disorders. These studies will provide a better understanding of reproductive development and lead to improved management of disorders of reproductive function, and may also aid in the development of innovative approaches to contraception.