Bimodal inhibition of connexin 43 gap junctions decreases ACTH-induced steroidogenesis and increases bovine adrenal cell population growth.
In order to elucidate the role of gap junctions in adrenal cell responses, we measured the effect of inhibiting gap junctions with 18-alpha glycerrhetinic acid (GA; a potent inhibitor of cell-cell communication) and connexin antisense transfection on cell proliferation and adrenocorticotropin (ACTH)-stimulated steroidogenesis. In these experiments we utilized a bovine adrenocortical cell (SBAC) population, which responds to ACTH treatment with a dose-dependent increase in steroid production, an increase in connexin 43 (alpha(1)-Cx43) gap junction protein concentrations, and a decrease in cell population growth. SBAC cell populations treated with GA had increased growth rates, decreased ACTH-stimulated steroidogenesis, but no reduction in alpha(1)-Cx43 gap junction protein contents. In contrast, when SBAC cells were transfected with alpha(1)-Cx43 antisense cDNA, gap junction protein concentration was dramatically reduced as expected, unlike the GA-treated cell populations. Cell populations transfected with alpha(1)-Cx43-antisense also exhibited increased growth rates and a decreased steroidogenic response to ACTH treatment as compared with control or vector-only transfected cell populations. The decreased responsiveness and increased number of cells in the population after gap junction function was decreased by either GA treatment or antisense transfection, suggests that gap junctions may be necessary factors in ACTH-stimulated responsiveness and growth control in the adrenal gland.
Shah
U S
US
Department of Cell Biology and Physiology, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania 15261, USA.
Murray
S A
SA
D000311:Adrenal Glands / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D002450:Cell Communication / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism*; D003864:Depression, Chemical; D017629:Gap Junctions / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008856:Microscopy, Fluorescence; D016376:Oligonucleotides, Antisense; D013256:Steroids / Q000096:biosynthesis; D014162:Transfection
D018031:Connexin 43; D016376:Oligonucleotides, Antisense; D013256:Steroids; C119129:18alpha-glycyrrhetinic acid; D000324:Adrenocorticotropic Hormone; D006034:Glycyrrhetinic Acid