Heme oxygenase-derived carbon monoxide modulates gonadotropin-releasing hormone release in immortalized hypothalamic neurons. 2010

Stefania Errico, and Rugia Shohreh, and Eugenio Barone, and Angela Pusateri, and Nadia Mores, and Cesare Mancuso
Institute of Pharmacology, Catholic University School of Medicine, Largo Francesco Vito, 1-00168 Roma, Italy.

Heme oxygenase (HO), the main enzyme deputed to heme metabolism, has been identified as two main isoforms called HO-1 and HO-2 both present in the central nervous system. Heme oxygenase has been shown to regulate the hypothalamic release of neuropeptides such as corticotrophin-releasing hormone and arginin-vasopressin. The aim of this study was to investigate and further characterize the presence of HO in gonadotropin-releasing hormone (GnRH) secreting hypothalamic neurons, GT1-7 and the role of HO by-products on GnRH secretion. The pulsatile release of GnRH from scattered hypothalamic neurons is the key regulator of mammalian fertility in the central nervous system. GT1-7 cells are immortalized hypothalamic neurons, characterized by spontaneous electrical activity and pulsatile GnRH release, resembling the central control pathway of the hypothalamic pituitary gonadal axis (HPG) in mammals. Hemin, the substrate of HO, significantly stimulated HO activity in static cultures, causing a rapid increase in GnRH release. Neither biliverdin nor bilirubin were able to mimic this rapid stimulatory effect, which was instead caused by carbon monoxide. Evidence of a possible involvement of prostaglandin E(2) in the HO by-product modulated GnRH secretion was reported. The hemin-evoked effect on GT1-7 neurons suggests a direct activity of HO by-products on the hypothalamic neuropeptide secretion, and claims for a possible role of CO in both the modulation of gonadotropin secretion and crosstalk among HPG and stress axis within the mammalian hypothalamus.

UI MeSH Term Description Entries
D007031 Hypothalamus Ventral part of the DIENCEPHALON extending from the region of the OPTIC CHIASM to the caudal border of the MAMMILLARY BODIES and forming the inferior and lateral walls of the THIRD VENTRICLE. Lamina Terminalis,Preoptico-Hypothalamic Area,Area, Preoptico-Hypothalamic,Areas, Preoptico-Hypothalamic,Preoptico Hypothalamic Area,Preoptico-Hypothalamic Areas
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
D008565 Membrane Proteins Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. Cell Membrane Protein,Cell Membrane Proteins,Cell Surface Protein,Cell Surface Proteins,Integral Membrane Proteins,Membrane-Associated Protein,Surface Protein,Surface Proteins,Integral Membrane Protein,Membrane Protein,Membrane-Associated Proteins,Membrane Associated Protein,Membrane Associated Proteins,Membrane Protein, Cell,Membrane Protein, Integral,Membrane Proteins, Integral,Protein, Cell Membrane,Protein, Cell Surface,Protein, Integral Membrane,Protein, Membrane,Protein, Membrane-Associated,Protein, Surface,Proteins, Cell Membrane,Proteins, Cell Surface,Proteins, Integral Membrane,Proteins, Membrane,Proteins, Membrane-Associated,Proteins, Surface,Surface Protein, Cell
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
D002248 Carbon Monoxide Carbon monoxide (CO). A poisonous colorless, odorless, tasteless gas. It combines with hemoglobin to form carboxyhemoglobin, which has no oxygen carrying capacity. The resultant oxygen deprivation causes headache, dizziness, decreased pulse and respiratory rates, unconsciousness, and death. (From Merck Index, 11th ed) Monoxide, Carbon
D006427 Hemin Chloro(7,12-diethenyl-3,8,13,17-tetramethyl-21H,23H-porphine-2,18-dipropanoato(4-)-N(21),N(22),N(23),N(24)) ferrate(2-) dihydrogen. Ferriprotoporphyrin,Hematin,Alkaline Hematin D-575,Chlorohemin,Ferrihaem,Ferriheme Chloride,Ferriprotoporphyrin IX,Ferriprotoporphyrin IX Chloride,Panhematin,Protohemin,Protohemin IX,Alkaline Hematin D 575,Chloride, Ferriheme,Chloride, Ferriprotoporphyrin IX,Hematin D-575, Alkaline
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001663 Bilirubin A bile pigment that is a degradation product of HEME. Bilirubin IX alpha,Bilirubin, (15E)-Isomer,Bilirubin, (4E)-Isomer,Bilirubin, (4E,15E)-Isomer,Bilirubin, Calcium Salt,Bilirubin, Disodium Salt,Bilirubin, Monosodium Salt,Calcium Bilirubinate,Hematoidin,delta-Bilirubin,Bilirubinate, Calcium,Calcium Salt Bilirubin,Disodium Salt Bilirubin,Monosodium Salt Bilirubin,Salt Bilirubin, Calcium,delta Bilirubin
D015232 Dinoprostone The most common and most biologically active of the mammalian prostaglandins. It exhibits most biological activities characteristic of prostaglandins and has been used extensively as an oxytocic agent. The compound also displays a protective effect on the intestinal mucosa. PGE2,PGE2alpha,Prostaglandin E2,Prostaglandin E2alpha,PGE2 alpha,Prepidil Gel,Prostaglandin E2 alpha,Prostenon,E2 alpha, Prostaglandin,E2, Prostaglandin,E2alpha, Prostaglandin,Gel, Prepidil,alpha, PGE2,alpha, Prostaglandin E2
D045744 Cell Line, Tumor A cell line derived from cultured tumor cells. Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines

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