title: Exploring the cyclooxygenase 2 (COX2)/15d-Δ(12,14)PGJ(2) system in hamster Sertoli cells: regulation by FSH/testosterone and relevance to glucose uptake.
abstract: We have previously described a stimulatory effect of testosterone on cyclooxygenase 2 (COX2) expression and prostaglandin (PG) synthesis, and the involvement of PGs in the modulation of testosterone production in Leydig cells of the seasonal breeder Syrian hamster. In this study, we investigated the existence of a COX2/PGs system in hamster Sertoli cells, its regulation by testosterone and FSH, and its effect on glucose uptake. COX2 expression was observed in Sertoli cells of both reproductively active and inactive adult hamsters. Testosterone and the plasma membrane-impermeable testosterone-BSA significantly induced COX2 expression, mitogen activated protein kinases 1/2 (MAPK1/2) phosphorylation and 15d-Δ(12,14)PGJ(2) production in Sertoli cells purified from photoperiodically regressed hamsters. These actions were abolished by the antiandrogen bicalutamide and by the inhibitor of MAPK kinase (MEK1/2) U0126, suggesting that testosterone exerts its stimulatory effect on COX2/PGs through a non-classical mechanism that involves the presence of androgen receptors and MAPK1/2 activation. FSH also stimulated COX2/PGs via MAPK1/2 phosphorylation. FSH and testosterone stimulate, whereas 15d-Δ(12,14)PGJ(2) via PPARγ inhibits, [2,6-(3)H]-2-deoxy-d-glucose ([(3)H]-2-DOG) uptake. Meloxicam, a selective COX2 inhibitor, further increases [(3)H]-2-DOG uptake in the presence of FSH or testosterone. Thus, in addition to their positive effect, FSH and testosterone may also exert an indirect negative regulation on glucose uptake which involves the COX2/15d-Δ(12,14)PGJ(2)/PPARγ system. Overall, these results demonstrate the presence of a COX2/PG system in hamster Sertoli cells which might act as a local modulator of FSH and testosterone actions.
authors.affiliation: Instituto de Biología y Medicina Experimental, CONICET, Vuelta de Obligado 2490 (1428), Ciudad de Buenos Aires, Argentina.
authors.forename: María Eugenia
authors.initials: ME
authors.lastname: Matzkin
authors.forename: Eliana Herminia
authors.initials: EH
authors.lastname: Pellizzari
authors.forename: Soledad Paola
authors.initials: SP
authors.lastname: Rossi
authors.forename: Ricardo Saúl
authors.initials: RS
authors.lastname: Calandra
authors.forename: Selva Beatriz
authors.initials: SB
authors.lastname: Cigorraga
authors.forename: Mónica Beatriz
authors.initials: MB
authors.lastname: Frungieri
mesh_terms: D000726:Androgen Antagonists / Q000494:pharmacology; D000813:Anilides / Q000494:pharmacology; D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D006224:Cricetinae; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D003847:Deoxyglucose / Q000378:metabolism; D005640:Follicle Stimulating Hormone / Q000502:physiology*; D005947:Glucose / Q000378:metabolism*; D048369:MAP Kinase Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048370:MAP Kinase Kinase 2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D000077239:Meloxicam; D008647:Mesocricetus / Q000502:physiology*; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000502:physiology; D012708:Sertoli Cells / Q000378:metabolism; D013739:Testosterone / Q000502:physiology*; D013843:Thiazines / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D014105:Tosyl Compounds / Q000494:pharmacology
chemical_list: C097240:15-deoxy-delta(12,14)-prostaglandin J2; D000726:Androgen Antagonists; D000813:Anilides; D002070:Butadienes; D009570:Nitriles; D013843:Thiazines; D013844:Thiazoles; D014105:Tosyl Compounds; C113580:U 0126; D013739:Testosterone; D005640:Follicle Stimulating Hormone; D003847:Deoxyglucose; C053541:bicalutamide; D051546:Cyclooxygenase 2; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2; D005947:Glucose; D015230:Prostaglandin D2; D000077239:Meloxicam