Cetrorelix, a gonadotropin-releasing hormone antagonist, induces the expression of melatonin receptor 1a in the gonadotropin-releasing hormone neuronal cell line GT1-7. 2009

Hirotaka Ishii, and Shun Sato, and Chengzhu Yin, and Yasuo Sakuma, and Masakatsu Kato
Department of Physiology, Nippon Medical School, Tokyo, Japan. hirotaka@nms.ac.jp

Melatonin has been implicated in the control of the reproductive system, and the modulatory actions of melatonin on gonadotropin-releasing hormone (GnRH) neurons have been assumed to be indirectly mediated through afferent neurons. However, our previous studies demonstrate sexually dimorphic modulation of A-type gamma-aminobutyric acid (GABA) receptor (GABA(A)R) currents by melatonin in adult rat GnRH neurons and a preferential expression of melatonin 1a receptor (MT1) in male GnRH neurons. Using immortalized GnRH neurons (GT1-7 cells), the present study investigated the mechanism by which the expression of melatonin receptors is regulated in GnRH neurons. Like endogenous GnRH neurons, GT1-7 cells express both GnRH and GnRH receptor mRNAs, indicating that the cells have a self-stimulatory system. A 2-iodomelatonin binding assay and RT-PCR analysis demonstrated that the cells expressed neither MT1 nor MT2. However, treatment of GT1-7 cells with the GnRH antagonist cetrorelix significantly increased 2-iodomelatonin binding and induced a time- and concentration-dependent MT1 mRNA expression. The GABA(A)R currents were then measured using a perforated patch-clamp technique to examine whether the treatment with cetrorelix changed the responses to melatonin. Melatonin augmented the GABA(A)R currents in GT1-7 cells treated with 1 muM cetrorelix for 24 h, while melatonin decreased the currents in the cells not treated with cetrorelix, probably via receptor-independent processes. The present results suggest that GnRH downregulates the expression of MT1 via an autocrine-paracrine mechanism in GT1-7 cells, and modifies the melatonin-induced modulation of GABA(A)R currents. These findings may provide one possible mechanism for the sexually dimorphic responses to melatonin in adult rat GnRH neurons.

UI MeSH Term Description Entries
D007987 Gonadotropin-Releasing Hormone A decapeptide that stimulates the synthesis and secretion of both pituitary gonadotropins, LUTEINIZING HORMONE and FOLLICLE STIMULATING HORMONE. GnRH is produced by neurons in the septum PREOPTIC AREA of the HYPOTHALAMUS and released into the pituitary portal blood, leading to stimulation of GONADOTROPHS in the ANTERIOR PITUITARY GLAND. FSH-Releasing Hormone,GnRH,Gonadoliberin,Gonadorelin,LH-FSH Releasing Hormone,LHRH,Luliberin,Luteinizing Hormone-Releasing Hormone,Cystorelin,Dirigestran,Factrel,Gn-RH,Gonadorelin Acetate,Gonadorelin Hydrochloride,Kryptocur,LFRH,LH-RH,LH-Releasing Hormone,LHFSH Releasing Hormone,LHFSHRH,FSH Releasing Hormone,Gonadotropin Releasing Hormone,LH FSH Releasing Hormone,LH Releasing Hormone,Luteinizing Hormone Releasing Hormone,Releasing Hormone, LHFSH
D008550 Melatonin A biogenic amine that is found in animals and plants. In mammals, melatonin is produced by the PINEAL GLAND. Its secretion increases in darkness and decreases during exposure to light. Melatonin is implicated in the regulation of SLEEP, mood, and REPRODUCTION. Melatonin is also an effective antioxidant.
D008564 Membrane Potentials The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization). Resting Potentials,Transmembrane Potentials,Delta Psi,Resting Membrane Potential,Transmembrane Electrical Potential Difference,Transmembrane Potential Difference,Difference, Transmembrane Potential,Differences, Transmembrane Potential,Membrane Potential,Membrane Potential, Resting,Membrane Potentials, Resting,Potential Difference, Transmembrane,Potential Differences, Transmembrane,Potential, Membrane,Potential, Resting,Potential, Transmembrane,Potentials, Membrane,Potentials, Resting,Potentials, Transmembrane,Resting Membrane Potentials,Resting Potential,Transmembrane Potential,Transmembrane Potential Differences
D009474 Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM. Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D011963 Receptors, GABA-A Cell surface proteins which bind GAMMA-AMINOBUTYRIC ACID and contain an integral membrane chloride channel. Each receptor is assembled as a pentamer from a pool of at least 19 different possible subunits. The receptors belong to a superfamily that share a common CYSTEINE loop. Benzodiazepine-Gaba Receptors,GABA-A Receptors,Receptors, Benzodiazepine,Receptors, Benzodiazepine-GABA,Receptors, Diazepam,Receptors, GABA-Benzodiazepine,Receptors, Muscimol,Benzodiazepine Receptor,Benzodiazepine Receptors,Benzodiazepine-GABA Receptor,Diazepam Receptor,Diazepam Receptors,GABA(A) Receptor,GABA-A Receptor,GABA-A Receptor alpha Subunit,GABA-A Receptor beta Subunit,GABA-A Receptor delta Subunit,GABA-A Receptor epsilon Subunit,GABA-A Receptor gamma Subunit,GABA-A Receptor rho Subunit,GABA-Benzodiazepine Receptor,GABA-Benzodiazepine Receptors,Muscimol Receptor,Muscimol Receptors,delta Subunit, GABA-A Receptor,epsilon Subunit, GABA-A Receptor,gamma-Aminobutyric Acid Subtype A Receptors,Benzodiazepine GABA Receptor,Benzodiazepine Gaba Receptors,GABA A Receptor,GABA A Receptor alpha Subunit,GABA A Receptor beta Subunit,GABA A Receptor delta Subunit,GABA A Receptor epsilon Subunit,GABA A Receptor gamma Subunit,GABA A Receptor rho Subunit,GABA A Receptors,GABA Benzodiazepine Receptor,GABA Benzodiazepine Receptors,Receptor, Benzodiazepine,Receptor, Benzodiazepine-GABA,Receptor, Diazepam,Receptor, GABA-A,Receptor, GABA-Benzodiazepine,Receptor, Muscimol,Receptors, Benzodiazepine GABA,Receptors, GABA A,Receptors, GABA Benzodiazepine,delta Subunit, GABA A Receptor,epsilon Subunit, GABA A Receptor,gamma Aminobutyric Acid Subtype A Receptors
D011966 Receptors, LHRH Receptors with a 6-kDa protein on the surfaces of cells that secrete LUTEINIZING HORMONE or FOLLICLE STIMULATING HORMONE, usually in the adenohypophysis. LUTEINIZING HORMONE-RELEASING HORMONE binds to these receptors, is endocytosed with the receptor and, in the cell, triggers the release of LUTEINIZING HORMONE or FOLLICLE STIMULATING HORMONE by the cell. These receptors are also found in rat gonads. INHIBINS prevent the binding of GnRH to its receptors. GnRH Receptors,Gonadoliberin Receptors,Gonadorelin Receptors,Gonadotropin Releasing-Hormone Receptors,LHFSHRH Receptors,LHRH Receptors,Luliberin Receptors,Receptors, GnRH,Receptors, Gonadoliberin,Receptors, Gonadorelin,Receptors, Luliberin,Follicle Stimulating Hormone-Releasing Hormone Receptors,GnRH Receptor,Gonadorelin Receptor,Gonadotropin-Releasing Hormone Receptor,LHRH Receptor,Luteinizing Hormone Releasing Hormone Receptors,Luteinizing Hormone Releasing-Hormone Receptor,Receptor, LHRH,Receptors, Gonadotropin Releasing-Hormone,Receptors, LHFSHRH,Follicle Stimulating Hormone Releasing Hormone Receptors,Gonadotropin Releasing Hormone Receptor,Gonadotropin Releasing Hormone Receptors,Hormone Receptor, Gonadotropin-Releasing,Luteinizing Hormone Releasing Hormone Receptor,Receptor, GnRH,Receptor, Gonadorelin,Receptor, Gonadotropin-Releasing Hormone,Receptors, Gonadotropin Releasing Hormone,Releasing-Hormone Receptors, Gonadotropin
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D002492 Central Nervous System Depressants A very loosely defined group of drugs that tend to reduce the activity of the central nervous system. The major groups included here are ethyl alcohol, anesthetics, hypnotics and sedatives, narcotics, and tranquilizing agents (antipsychotics and antianxiety agents). CNS Depressants,Depressants, CNS
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D006727 Hormone Antagonists Chemical substances which inhibit the function of the endocrine glands, the biosynthesis of their secreted hormones, or the action of hormones upon their specific sites. Antagonists, Hormone

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