Activation of Cl(-) channels by human chorionic gonadotropin in luteinized granulosa cells of the human ovary modulates progesterone biosynthesis
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 rectifying Cl- current. Exposure of human granulosa cells to hCG induced a rapid 4,4â€²-diisothiocyanatostilbene-2,2-disulphonic acid-sensitive cell membrane depolarization that was paralleled with an approximately 20% decrease in cell volume. Treatment with hCG evoked oscillatory and nonoscillatory intracellular Ca2+ signals in human granulosa cells. Extracellular Ca2+ removal and 4,4â€²- diisothiocyanatostilbene-2,2-disulphonic acid abolished the nonoscillatory component while leaving the Ca2+ oscillations unaffected. It is concluded that human granulosa cells express functional the volume-sensitive outwardly rectifying Cl- channels that are activated by hCG, which are critical for plasma membrane potential changes, Ca2+ influx, and P4 production. Copyright Â© 2008 by The Endocrine Society.
|Título según WOS:||Activation of Cl(-) channels by human chorionic gonadotropin in luteinized granulosa cells of the human ovary modulates progesterone biosynthesis|
|Título según SCOPUS:||Activation of Cl- channels by human chorionic gonadotropin in luteinized granulosa cells of the human ovary modulates progesterone biosynthesis|
|Título de la Revista:||ENDOCRINOLOGY|
|Fecha de publicación:||2008|
|Página de inicio:||4680|