Activation of Cl- channels by human chorionic gonadotropin in luteinized granulosa cells of the human ovary modulates progesterone biosynthesis

Abstract

Chloride permeability pathways and progesterone (P4) secretion elicited by human chorionic gonadotropin (hCG) in human granulosa cells were studied by electrophysiological techniques and single-cell volume, membrane potential and Ca2+i measurements. Reduction in extracellular Cl - and equimolar substitution by the membrane-impermeant anions glutamate or gluconate significantly increased hCG-stimulated P4 accumulation. A similar result was achieved by exposing the cells to hCG in the presence of a hypotonic extracellular solution. Conversely, P4 accumulation was drastically reduced in cells challenged with hCG exposed to a hypertonic solution. Furthermore, conventional Cl- channel inhibitors abolished hCG-mediated P4 secretion. In contrast, 25-hydroxycholesterol-mediated P4 accumulation was unaffected by Cl- channel blockers. In human granulosa cells, hCG triggered the activation of a tamoxifen-sensitive outwardly rectifying Cl- current comparable to the volume-sensitive outwardly recti