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Identification and Characterization of a Gonadotropin-Inhibitory System in the Brains of Mammals
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Identification and Characterization of a Gonadotropin-Inhibitory System in the Brains of Mammals
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Journal Article
Identification and Characterization of a Gonadotropin-Inhibitory System in the Brains of Mammals
2006
Overview
Successful reproduction requires maintenance of the reproductive axis within fine operating limits through negative feedback actions of sex steroids. Despite the importance of this homeostatic process, our understanding of the neural loci, pathways, and neurochemicals responsible remain incomplete. Here, we reveal a neuropep-tidergic pathway that directly links gonadal steroid actions to regulation of the reproductive system. An RFamide (Arg-Phe-NH₂) peptide that inhibits gonadotropin release from quail pituitary was recently identified and named gonadotropin-inhibitory hormone (GnlH). Birds are known to have specialized adaptations associated with gonadotropin-releasing hormone (GnRH) regulation to optimize reproduction (e.g., encephalic photoreceptors), and the existence of a hypothalamic peptide inhibiting gonadotropins may or may not be another such specialization. To determine whether GnlH serves as a signaling pathway for sex steroid regulation of the reproductive axis, we used immunohistochemistry and in situ hybridization to characterize the distribution and functional role of this peptide in hamsters, rats, and mice. GnlH-immunoreactive (GnlH-ir) cell bodies are clustered in the mediobasal hypothalamus with pronounced projections and terminals throughout the CNS. In vivo GnlH administration rapidly inhibits luteinizing hormone secretion. Additionally, GnlH-ir neurons form close appositions with GnRH cells, suggesting a direct means of GnRH modulation. Finally, GnlH-ir cells express estrogen receptor-α and exhibit robust immediate early gene expression after gonadal hormone stimulation. Taken together, the distribution of GnlH efferents to neural sites regulating reproductive behavior and neuroendocrine secretions, expression of steroid receptors in GnlH-ir nuclei, and GnlH inhibition of luteinizing hormone secretion indicate the discovery of a system regulating the mammalian reproductive axis.
Publisher
National Academy of Sciences,National Acad Sciences
Subject
/ Animals
/ Brain
/ Female
/ Gonadal Steroid Hormones - pharmacology
/ Gonadotropins - antagonists & inhibitors
/ Hamsters
/ Hypothalamic Hormones - analysis
/ Hypothalamic Hormones - genetics
/ Hypothalamic Hormones - metabolism
/ Luteinizing Hormone - antagonists & inhibitors
/ Luteinizing Hormone - secretion
/ Mammalia
/ Mammals
/ Mice
/ Neurons
/ Peptides
/ Rats
/ Receptors, Steroid - drug effects
/ Receptors, Steroid - genetics
/ Rodents
/ Steroids
