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* Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York, New York 10029; and Division of Pharmacology and Toxicology, College of Pharmacy, Institute for Neuroscience, and Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, Texas 78712
To whom requests for reprints should be addressed at 1 The University of Texas at Austin, Division of Pharmacology/Toxicology, 1 University Station, A1915, Austin, TX 78712. E-mail: andrea.gore{at}mail.utexas.edu
Given the close relationship among neuroendocrine systems, it is likely that there may be common signals that coordinate the acquisition of adult reproductive function with other homeostatic processes. In this review, we focus on central nervous system insulin-like growth factor–1 (IGF-1) as a signal controlling reproductive function, with possible links to somatic growth, particularly during puberty. In vertebrates, the appropriate neurosecretion of the decapeptide gonadotropin-releasing hormone (GnRH) plays a critical role in the progression of puberty. Gonadotropin-releasing hormone is released in pulses from neuroterminals in the median eminence (ME), and each GnRH pulse triggers the production of the gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH). These pituitary hormones in turn stimulate the synthesis and release of sex steroids by the gonads. Any factor that affects GnRH or gonadotropin pulsatility is important for puberty and reproductive function and, among these factors, the neurotrophic factor IGF-1 is a strong candidate. Although IGF-1 is most commonly studied as the tertiary peripheral hormone in the somatotropic axis via its synthesis in the liver, IGF-1 is also synthesized in the brain, within neurons and glia. In neuroendocrine brain regions, central IGF-1 plays roles in the regulation of neuroendocrine functions, including direct actions on GnRH neurons. Moreover, GnRH neurons themselves co-express IGF-1 and the IGF-1 receptor, and this expression is developmentally regulated. Here, we examine the role of IGF-1 acting in the hypothalamus as a critical link between reproductive and other neuroendocrine functions.
Key Words: insulin-like growth factor–1 • gonadotropin-releasing hormone • hypothalamus • preoptic area • puberty • reproduction
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