Marlene Vind Hofmeister
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Helle Hasager Damkier
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Birgitte Mønster Christensen
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Björn Olde
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L. M. Fredrik Leeb-Lundberg
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Steroid hormones such as 17β-estradiol (E2) are known to modulate ion transporter expression in the kidney through classic intracellular receptors. Steroid hormones are also known to cause rapid nongenomic responses in a variety of nonrenal tissues. However, little is known about renal short-term effects of steroid hormones. Here, we studied the acute actions of E2 on intracellular Ca2+ signaling in isolated distal convoluted tubules (DCT2), connecting tubules (CNT), and initial cortical collecting ducts (iCCD) by fluo 4 fluorometry. Physiological concentrations of E2 induced transient increases in intracellular Ca2+ concentration ([Ca2+]i) in a subpopulation of cells. The [Ca2+]i increases required extracellular Ca2+ and were inhibited by Gd3+. Strikingly, the classic E2 receptor antagonist ICI 182,780 also increased [Ca2+]i, which is inconsistent with the activation of classic E2 receptors. G protein-coupled estrogen receptor 1 (GPER1 or GPR30) was detected in microdissected DCT2/CNT/iCCD by RT-PCR. Stimulation with the specific GPER1 agonist G-1 induced similar [Ca2+]i increases as E2, and in tubules from GPER1 knockout mice, E2, G-1, and ICI 182,780 failed to induce [Ca2+]i elevations. The intercalated cells showed both E2-induced concanamycin-sensitive H+-ATPase activity by BCECF fluorometry and the E2-mediated [Ca2+]i increment. We propose that E2 via GPER1 evokes [Ca2+]i transients and increases H+-ATPase activity in intercalated cells in mouse DCT2/CNT/iCCD.
Effects of 17β-Estradiol on Mitophagy in the Murine MC3T3-E1 Osteoblast Cell Line is Mediated via G Protein-Coupled Estrogen Receptor and the ERK1/2 Signaling Pathway
