Effect of loop diuretics and nonsteroidal antiinflammatory drugs on thyrotropin release by rat anterior pituitary cells in vitro. 1995

C F Lim, and N M Loidl, and J A Kennedy, and D J Topliss, and J R Stokigt
Ewen Downie Metabolic Unit, Alfred Hospital, Melbourne, Victoria, Australia.

The close inverse-feedback relationship between serum free thyroxine (T4) and thyrotropin (TSH) is altered in some patients receiving therapeutic doses of drugs such as furosemide, fenclofenac, and diphenylhydantoin. We therefore examined the effect of nonsteroidal antiinflammatory drugs (NSAID), diuretics, and diphenylhydantoin on TSH release in rat anterior pituitary cells in primary culture. TSH content of the culture medium was measured at 22 hours at 37 degrees C either with or without thyrotropin-releasing hormone ([TRH] 10 nmol/L) in medium containing 0.5% bovine serum albumin. The mean basal TSH release by pituitary cells was 6.2 +/- 1.2 ng/mL (n = 10) and was not influenced by unlabeled triiodothyronine ([T3] 100 nmol/L) or any of the drugs tested at < or = 400 mumol/L, except ethyacrynic acid. TRH 10 nmol/L increased mean TSH release by 346% +/- 95% (n = 10). T3 1 and 100 nmol/L inhibited TRH-stimulated TSH release by 24% and 31%, respectively (P < .001), whereas TRH-stimulated TSH release was inhibited by 100 mumol/L meclofenamic acid (29%), fenclofenac (28%), furosemide (24%), and diphenylhydantoin (48%) (P < .001 v TRH alone). Meclofenamic acid and furosemide (100 mumol/L) did not significantly alter the inhibitory effect of T3 1 nmol/L on TRH-stimulated TSH release. These in vitro studies suggest that meclofenamic acid, fenclofenac, furosemide, and diphenylhydantoin could influence TSH release by attenuating the TSH response to TRH. This effect may influence T4-TSH relationships when these agents are used in vivo.

UI MeSH Term Description Entries
D008297 Male Males
D008469 Meclofenamic Acid A non-steroidal anti-inflammatory agent with antipyretic and antigranulation activities. It also inhibits prostaglandin biosynthesis. Benzoic acid, 2-((2,6-dichloro-3-methylphenyl)amino)-, monosodium salt, monohydrate,Meclofenamate,Meclofenamate Sodium,Meclofenamate Sodium Anhydrous,Meclofenamate Sodium Monohydrate,Meclomen,Sodium Meclofenamate,Meclofenamate, Sodium
D010648 Phenylacetates Derivatives of phenylacetic acid. Included under this heading are a variety of acid forms, salts, esters, and amides that contain the benzeneacetic acid structure. Note that this class of compounds should not be confused with derivatives of phenyl acetate, which contain the PHENOL ester of ACETIC ACID. Benzeneacetates,Benzeneacetic Acids,Phenylacetic Acids,Acids, Benzeneacetic,Acids, Phenylacetic
D010672 Phenytoin An anticonvulsant that is used to treat a wide variety of seizures. It is also an anti-arrhythmic and a muscle relaxant. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. The mechanism of its muscle relaxant effect appears to involve a reduction in the sensitivity of muscle spindles to stretch. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs. Diphenylhydantoin,Fenitoin,Phenhydan,5,5-Diphenylhydantoin,5,5-diphenylimidazolidine-2,4-dione,Antisacer,Difenin,Dihydan,Dilantin,Epamin,Epanutin,Hydantol,Phenytoin Sodium,Sodium Diphenylhydantoinate,Diphenylhydantoinate, Sodium
D010903 Pituitary Gland, Anterior The anterior glandular lobe of the pituitary gland, also known as the adenohypophysis. It secretes the ADENOHYPOPHYSEAL HORMONES that regulate vital functions such as GROWTH; METABOLISM; and REPRODUCTION. Adenohypophysis,Anterior Lobe of Pituitary,Anterior Pituitary Gland,Lobus Anterior,Pars Distalis of Pituitary,Adenohypophyses,Anterior Pituitary Glands,Anterior, Lobus,Anteriors, Lobus,Lobus Anteriors,Pituitary Anterior Lobe,Pituitary Glands, Anterior,Pituitary Pars Distalis
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
D004232 Diuretics Agents that promote the excretion of urine through their effects on kidney function. Diuretic,Diuretic Effect,Diuretic Effects,Effect, Diuretic,Effects, Diuretic
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
D005665 Furosemide A benzoic-sulfonamide-furan. It is a diuretic with fast onset and short duration that is used for EDEMA and chronic RENAL INSUFFICIENCY. Frusemide,Fursemide,Errolon,Frusemid,Furanthril,Furantral,Furosemide Monohydrochloride,Furosemide Monosodium Salt,Fusid,Lasix
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

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