title: Biphasic effect of nitric oxide on testosterone and cyclic GMP production by purified rat Leydig cells cultured in vitro.
abstract: Nitric oxide (NO) biphasically modulates osteoclast function and sperm motility by exerting a positive effect at low concentrations and a negative effect at high concentrations. We therefore tested whether NO exerts a comparable effect on testosterone secretion by cultured rat Leydig cells. Three NO-donors, S-nitroso-N-acetylpenicillamine (SNAP), diethylamine/nitric oxide complex sodium salt (DEA/NO) and diethylenetriamine nitric oxide adduct (DETA/NO) were administered in a wide range of concentrations (10(-8)-10(-3) M for 3 h) to Percoll-purified Leydig cells from adult rats. These drugs raised testosterone and cGMP secretion when used at low concentrations (10(-8)-10(-5) M); however, they inhibited testosterone, but did not affect cGMP, secretion at concentrations higher than 10(-5) M. Administration of the NO scavenger haemoglobin (160 micrograms/mL) prevented both the stimulatory and the inhibitory effect of these drugs. Nitrite accumulation was measured as a marker of NO released by the drugs in our in vitro system; it fell within the range of control media in the presence of NO-donor concentrations lower than 10(-5) M, but was several-fold higher in the media of cells treated with concentrations of the NO-donors greater than 10(-5) M. These data show that (1) NO exerts a biphasic effect on testosterone secretion, which is stimulatory at low and inhibitory at high concentrations; (2) the stimulatory effect of NO is mediated by cGMP, the classic second messenger for NO action.
authors.affiliation: Department of Endocrinology and Metabolism, University School of Medicine of Genoa, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Valenti
authors.forename: C M
authors.initials: CM
authors.lastname: Cuttica
authors.forename: L
authors.initials: L
authors.lastname: Fazzuoli
authors.forename: G
authors.initials: G
authors.lastname: Giordano
authors.forename: M
authors.initials: M
authors.lastname: Giusti
mesh_terms: D000328:Adult; D000818:Animals; D002478:Cells, Cultured; D003470:Culture Media; D006152:Cyclic GMP / Q000096:biosynthesis*; D006801:Humans; D007985:Leydig Cells / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D011073:Polyamines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013739:Testosterone / Q000378:metabolism*
chemical_list: D003470:Culture Media; D009573:Nitrites; D011073:Polyamines; C110881:S-nitro-N-acetylpenicillamine; C005391:diethylenetriamine; D009569:Nitric Oxide; D013739:Testosterone; D010396:Penicillamine; D006152:Cyclic GMP