Carbachol induces homologous steroidogenic refractoriness of bovine fasciculata-reticularis cells.
Recently it was shown that the cholinergic agonist carbachol stimulates cortisol production in bovine ZFR cells via muscarinic receptor M(3). In the present study, we investigated the effect of chronic cholinergic stimulation on steroidogenic response and muscarinic receptor regulation in ZFR cells. Cortisol secretion of ZFR cells treated with 10(-4) M of carbachol decreased in a dose- and time-dependent manner. The carbachol-elicited loss of response was associated with a decrease in M(3) receptor number, which was also time- and dose-dependent. The down-regulation of the receptors was not associated with the decrease of M(3) receptor mRNA level. The marked steroidogenic desensitization caused by pretreatment of carbachol did not alter ACTH or angiotensin II activated steroid response. Northern blot analysis showed that carbachol pretreatment did not change the gene expression of P450scc, P450cl7, 3betaHSD and StAR mRNAs. These results suggest that carbachol induces homologous steroidogenic refractoriness of ZFR cells.
Janossy
A
A
Institute of Experimental Medicine, Hungarian Academy of Sciences, P.O. Box 67, H-1450, Budapest, Hungary. janossy@koki.hu
Saez
J M
JM
Li
J Y
JY
D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D002417:Cattle; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D006854:Hydrocortisone / Q000096:biosynthesis; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000235:genetics; D015290:Second Messenger Systems / Q000187:drug effects; D013256:Steroids / Q000096:biosynthesis; D015383:Zona Fasciculata / Q000166:cytology / Q000187:drug effects*; D015385:Zona Reticularis / Q000166:cytology / Q000187:drug effects*
D012333:RNA, Messenger; D011976:Receptors, Muscarinic; D013256:Steroids; D000804:Angiotensin II; D002217:Carbachol; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone