title: Regulation of angiotensin II receptors and steroidogenic responsiveness in cultured bovine fasciculata and glomerulosa adrenal cells.
abstract: The aim of the present study was to investigate the effect of several effectors on angiotensin II (A-II) receptors and steroidogenic responsiveness in cultured bovine fasciculata cells. Treatment of adrenal cells for 24 h with A-II (0.1 microM), corticotropin (1 nM), phorbol ester (PMA 0.1 microM), calcium ionophore A23187 (0.1 microM) and cyclic 8-bromoAMP (1 mM) produced a loss of A-II receptors whereas the A-II antagonist [Sar1-Ala8]A-II (0.1 microM) led to a small but significant increase. The extent of the down-regulation of receptors following maximal concentrations of A-II was greater than that produced by the other agents. The effects of A-II were dose-dependent with a ID50 of 3 nM. Since cycloheximide and actinomycin blocked the down-regulation of receptors, it seems likely that the effectors lead to the synthesis of certain proteins which inhibit the recycling of internalized receptors. Pretreatment of adrenal cells with A-II induced both homologous (90% decrease) and heterologous (corticotropin 83, PMA and ionophore 76% decrease) steroidogenic desensitization. However, the cAMP response to corticotropin of A-II-pretreated cells was higher (P less than 0.001) than for control cells. Pretreatment with PMA and A23187 also resulted in both homologous and heterologous steroidogenic refractoriness but to a lesser degree than that induced by A-II. In contrast, corticotropin-pretreated cells responded normally to further stimulation with corticotropin or A-II. Similarly pretreatment of bovine adrenal glomerulosa cells with A-II (1 nM and 0.1 microM) and corticotropin (1 nM) also induced A-II receptor loss and steroidogenic refractoriness. The present findings indicate that, in contrast to the results reported in vivo in the rat, where A-II leads to up-regulation of its own receptors on glomerulosa cells and increases steroidogenic responsiveness, this peptide results in both down-regulation and desensitization in cultured bovine fasciculata and glomerulosa cells. Our results also emphasize the absence of correlation between A-II receptor loss and steroidogenic responsiveness.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale Unité 307, Hôpital Debrousse, Lyon.
authors.forename: A
authors.initials: A
authors.lastname: Penhoat
authors.forename: C
authors.initials: C
authors.lastname: Jaillard
authors.forename: A
authors.initials: A
authors.lastname: Crozat
authors.forename: J M
authors.initials: JM
authors.lastname: Saez
mesh_terms: D000302:Adrenal Cortex / Q000187:drug effects / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002417:Cattle; D002478:Cells, Cultured; D003345:Corticosterone / Q000096:biosynthesis*; D000242:Cyclic AMP / Q000096:biosynthesis*; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D010703:Phorbol Esters / Q000494:pharmacology; D011945:Receptors, Angiotensin / Q000187:drug effects / Q000378:metabolism*
chemical_list: D010703:Phorbol Esters; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D003609:Dactinomycin; D000001:Calcimycin; D000324:Adrenocorticotropic Hormone; D003513:Cycloheximide; D000242:Cyclic AMP; D003345:Corticosterone