Biomaterial Database

Biphasic regulation of the gonadotropin-releasing hormone receptor by receptor microaggregation and intracellular Ca2+ levels. 1984

P M Conn, and D C Rogers, and S G Seay

In the present work we show that Ca2+ is both necessary and sufficient to evoke homologous up-regulation of the gonadotropin-releasing hormone (GnRH) receptor. Extracellular Ca2+ as well as RNA and protein synthesis were required for this event, and it was blocked by Ca2+ ion channel blockers. Drugs which stimulated increased intracellular Ca2+ levels also stimulated receptor up-regulation and enhanced responsiveness even in the absence of added GnRH. Such drugs were effective below the concentrations needed to evoke luteinizing hormone (LH) release, suggesting that enhanced levels of Ca2+ ion, rather than LH depletion, is the responsible agent. A GnRH antagonist did not evoke up- or down-regulation; however, a conjugate of this antagonist, which stimulated microaggregation of the GnRH receptor, also stimulated these biphasic actions. In contrast to up-regulation, down-regulation of the GnRH receptor appears to be Ca2+-independent and does not require RNA or protein synthesis. These data are consistent with a model in which microaggregation of the GnRH receptor is the final step in common to a branched pathway consisting of Ca2+-dependent (LH release, enhanced sensitivity, up-regulation) and Ca2+-independent (desensitization, down-regulation) events.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D007986	Luteinizing Hormone	A major gonadotropin secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). Luteinizing hormone regulates steroid production by the interstitial cells of the TESTIS and the OVARY. The preovulatory LUTEINIZING HORMONE surge in females induces OVULATION, and subsequent LUTEINIZATION of the follicle. LUTEINIZING HORMONE consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH and FSH), but the beta subunit is unique and confers its biological specificity.	ICSH (Interstitial Cell Stimulating Hormone),Interstitial Cell-Stimulating Hormone,LH (Luteinizing Hormone),Lutropin,Luteoziman,Luteozyman,Hormone, Interstitial Cell-Stimulating,Hormone, Luteinizing,Interstitial Cell Stimulating Hormone
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
D010902	Pituitary Gland	A small, unpaired gland situated in the SELLA TURCICA. It is connected to the HYPOTHALAMUS by a short stalk which is called the INFUNDIBULUM.	Hypophysis,Hypothalamus, Infundibular,Infundibular Stalk,Infundibular Stem,Infundibulum (Hypophysis),Infundibulum, Hypophyseal,Pituitary Stalk,Hypophyseal Infundibulum,Hypophyseal Stalk,Hypophysis Cerebri,Infundibulum,Cerebri, Hypophysis,Cerebrus, Hypophysis,Gland, Pituitary,Glands, Pituitary,Hypophyseal Stalks,Hypophyses,Hypophysis Cerebrus,Infundibular Hypothalamus,Infundibular Stalks,Infundibulums,Pituitary Glands,Pituitary Stalks,Stalk, Hypophyseal,Stalk, Infundibular,Stalks, Hypophyseal,Stalks, Infundibular
D011956	Receptors, Cell Surface	Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.	Cell Surface Receptor,Cell Surface Receptors,Hormone Receptors, Cell Surface,Receptors, Endogenous Substances,Cell Surface Hormone Receptors,Endogenous Substances Receptors,Receptor, Cell Surface,Surface Receptor, Cell
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
D002118	Calcium	A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.	Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D002478	Cells, Cultured	Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.	Cultured Cells,Cell, Cultured,Cultured Cell
D005260	Female		Females
D000001	Calcimycin	An ionophorous, polyether antibiotic from Streptomyces chartreusensis. It binds and transports CALCIUM and other divalent cations across membranes and uncouples oxidative phosphorylation while inhibiting ATPase of rat liver mitochondria. The substance is used mostly as a biochemical tool to study the role of divalent cations in various biological systems.	4-Benzoxazolecarboxylic acid, 5-(methylamino)-2-((3,9,11-trimethyl-8-(1-methyl-2-oxo-2-(1H-pyrrol-2-yl)ethyl)-1,7-dioxaspiro(5.5)undec-2-yl)methyl)-, (6S-(6alpha(2S,3S),8beta(R*),9beta,11alpha))-,A-23187,A23187,Antibiotic A23187,A 23187,A23187, Antibiotic