Regulation of gonadotropin-releasing hormone gene expression.
Reproductive function is influenced by several internal and external cues, which ultimately exert their effects on the gonadotropin-releasing hormone (GnRH) neuron. As the final common pathway in the brain for regulating reproduction, GnRH neurons receive signals from multiple cell types, and alterations in GnRH production impact reproductive competence. Historically, the paucity of GnRH neurons and their scattered distribution in the brain have limited the study of GnRH gene expression. With transgenic technology, newer model systems (such as immortalized GnRH-expressing cell lines and GnRH-reporter gene transgenic mice) have been developed, making molecular studies possible. This article provides an update on the molecular mechanisms responsible for the regulation of GnRH gene expression, focusing on tissue-specific expression and transcriptional regulation. After an overview of GnRH gene structure, synthesis, and secretion, the model systems for studying GnRH neurons are examined. The molecular mechanisms that translate physiologic stimuli, such as nutritional status or stress, into changes in GnRH expression will be reviewed, concentrating on the regulatory regions within the GnRH gene promoter and the critical transcription factors.
Kim
Helen H
HH
In Vitro Fertilization Program, Section of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, The University of Chicago, 5841 South Maryland, Chicago, IL 60637, USA. hkim@babies.bsd.uchicago.edu
D000818:Animals; D002460:Cell Line; D018507:Gene Expression Regulation, Developmental; D012739:Gonadal Steroid Hormones / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007031:Hypothalamus / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D009474:Neurons / Q000378:metabolism*; D009752:Nutritional Status / Q000235:genetics; D011401:Promoter Regions, Genetic; D012098:Reproduction / Q000235:genetics*; D015398:Signal Transduction; D013312:Stress, Physiological / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
D012739:Gonadal Steroid Hormones; D014157:Transcription Factors; D007987:Gonadotropin-Releasing Hormone