Effects of 18beta-glycyrrhetinic acid on the junctional complex and steroidogenesis in rat adrenocortical cells.
Cellular junctions play important roles in cell differentiation, signal transduction, and cell function. This study investigated their function in steroid secretion by adrenal cells. Immunofluorescence staining revealed the presence of gap junctions and adherens junctions between adrenal cells. The major gap junction protein, connexin43, was seen as a linear dotted pattern of the typical gap junction plaques, in contrast to alpha-, beta-, and gamma-catenin, which were seen as continuous, linear staining of cell-cell adherens junction. Treatment with 18beta-glycyrrhetinic acid, a gap junction inhibitor, reduced the immunoreactivity of these proteins in a time- and dose-dependent manner, and caused the gap junction and adherens junction to separate longitudinally from the cell-cell contact sites, indicating the structural interdependency of these two junctions. Interestingly, 18beta-glycyrrhetinic acid stimulated a two- to three-fold increase in steroid production in these adrenal cells lacking intact cell junctions. These data raise the question of the necessity for cell communication for the endocrine function of adrenal cells. Pharmacological analyses indicated that the steroidogenic effect of 18beta-glycyrrhetinic acid was partially mediated by extracellular signal-related kinase and calcium/calmodulin-dependent kinase, a pathway distinct from the protein kinase A signaling pathway already known to mediate steroidogenesis in adrenal cells.
Huang
Shih-Horng
SH
Far Eastern Memorial Hospital, Department of Surgery, Taipei, Taiwan 220, USA.
Wu
Jiahn-Chun
JC
Hwang
Ra-Der
RD
Yeo
Hui-Lin
HL
Wang
Seu-Mei
SM
D000302:Adrenal Cortex / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002450:Cell Communication / Q000502:physiology; D002478:Cells, Cultured; D018031:Connexin 43 / Q000378:metabolism; D003345:Corticosterone / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D051180:Desmoplakins; D004791:Enzyme Inhibitors / Q000378:metabolism; D005260:Female; D006034:Glycyrrhetinic Acid / Q000737:chemistry / Q000494:pharmacology*; D007365:Intercellular Junctions / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D013256:Steroids / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism; D051178:alpha Catenin; D051176:beta Catenin; D051185:gamma Catenin
D018031:Connexin 43; C495268:Ctnnb1 protein, rat; D003598:Cytoskeletal Proteins; D051180:Desmoplakins; D004791:Enzyme Inhibitors; D013256:Steroids; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin; D051185:gamma Catenin; D006034:Glycyrrhetinic Acid; D003345:Corticosterone