PS-BPB05-7: UPREGULATION OF ALDOSTERONE SYNTHASE INDUCED BY LUTEINIZING HORMONE IN HUMAN ADRENOCORTICAL CELLS

Abstract

Objective: Plasma aldosterone concentration (PAC) is increased in stages of elevation of luteinizing hormone (LH) during the luteal phase of the ovarian cycle, menopause, or pregnancy. PAC is elevated in patients with polycystic ovary syndrome who have elevated circulating concentration of luteinizing hormone (LH). In addition, stimulation of aldosterone production by LH has been reported. In the present study, we investigated the mechanism by which LH increases aldosterone production in human adrenocortical cells. Design and Methods: Immunohistochemical staining for CYP11B2, the aldosterone synthase, and LH receptor were performed using autopsy adrenal gland specimens. Changes in mRNA or protein expressions of CYP11B2 after treatment with LH, angiotensin (Ang) II, or LH+Ang were compared in human HAC15 adrenocortical cells. Effects of an Ang receptor blocker (ARB), adenylyl cyclase (AC) inhibitor, cyclic AMP response element binding protein (CREB) inhibitor, protein kinase A (PKA) inhibitor, or β;-catenin inhibitor on the increase in CYP11B2 mRNA expression induced by LH+Ang ll were investigated in these cells. In addition, effects of an AC agonist on CYP11B2 mRNA expression were investigated in these cells. Results: Immunostaining for LH receptor was detected in cells positive for CYP11B2 in adrenal granulosa and fasciculata region in the human autopsy specimens. CYP11B2 mRNA and protein expressions were significantly increased after treatment with LH+Ang ll than LH or Ang ll alone in HAC cells. Elevation of CYP11B2 mRNA expression induced by LH+Ang ll was completely suppressed by the ARB, AC inhibitor, or CREB inhibitor and was significantly reduced by the PKA inhibitor or β;-catenin inhibitor in these cells. CYP11B2 mRNA expression was significantly increased by the AC agonist. Conclusion: The present study showed that LH receptor is expressed in human adrenal cortical region and that LH augments CYP11B2 expression via AC-CREB pathway in the presence of Ang ll in human adrenocortical cells.