cyclic-gmp and 22-hydroxycholesterol

Fenvalerate is a widely used synthetic pyrethroid insecticide and is known to impede the male reproductive function. However, the mechanisms remain to be elucidated. In this study, mouse Leydig tumor cells (MLTC-1) were used to investigate the effects of fenvalerate on progesterone production. Fenvalerate treatment inhibited progesterone secretion induced by human chorionic gonadotropin (hCG), cholera toxin (CT) or forskolin and decreased cAMP levels induced by hCG, but not by CT or forskolin, which suggested a repaired site on the upstream components of G protein or G protein per se by fenvalerate in the cAMP-mediated signal pathway. Furthermore, the addition of cAMP analog, 8-Br-cAMP, could not reverse fenvalerate-suppressed progesterone synthesis, indicating that fenvalerate interfered with the downstream molecules of cAMP. In addition, fenvalerate decreased steroidogenic acute regulatory protein (StAR) mRNA and protein levels, and also profoundly inhibited the activity of P450 side chain cleavage enzyme (P450scc) which was consistent with the decreased expression of P450scc mRNA and protein in MLTC-1 cells. These results suggested that fenvalerate might inhibit progesterone production by attenuating cAMP generation and inhibiting StAR expression and P450scc activity.

Topics: Animals; Cell Line, Tumor; Cell Survival; Cholera Toxin; Cholesterol Side-Chain Cleavage Enzyme; Chorionic Gonadotropin; Colforsin; Cyclic AMP; Cyclic GMP; Dose-Response Relationship, Drug; Enzyme Inhibitors; Hydroxycholesterols; Insecticides; Leydig Cell Tumor; Male; Mice; Nitriles; Phosphoproteins; Pregnenolone; Progesterone; Pyrethrins; RNA, Messenger; Signal Transduction

The effects of L-arginine on corticosterone production, cGMP, and nitrite levels were examined in zona fasciculata adrenal cells. L-Arginine significantly decreased both basal and ACTH-stimulated corticosterone production. This effect was still evident when steroidogenesis was induced by 8-bromo-cAMP and 22(R)-hydroxycholesterol, but not in the presence of exogenously added pregnenolone. L-Arginine increased cGMP and nitrite levels,; these effects were blocked by the nitric oxide synthase inhibitor, N(G)-nitro-L-arginine methyl-ester. Transport of L-[3H]arginine was rapid, saturable, and monophasic, with an apparent Km of 163+/-14 microM and a maximum velocity of 53+/-6 pmol/min x 10(5) cells. The basic amino acids L-lysine and L-ornithine, but not D-arginine or the nitric oxide synthase inhibitors N(G)-nitro-L-arginine methyl-ester and N(G)-nitro-L-arginine, impaired L-arginine uptake. Taken together, these results suggest that steroidogenesis in zona fasciculata adrenal cells may be negatively modulated by L-arginine-derived nitric oxide.

Topics: 8-Bromo Cyclic Adenosine Monophosphate; Adrenocorticotropic Hormone; Animals; Arginine; Corticosterone; Cyclic GMP; Drug Synergism; Enzyme Inhibitors; Hydroxycholesterols; Lysine; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; Ornithine; Pregnenolone; Rats; Rats, Wistar; Zona Fasciculata