1. Desensitization of Pituitary Gonadotropin Secretion by Agonist-induced Inactivation of Voltage-sensitive Calcium Channels
- Author
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Kevin J. Catt, Eduardo Rojas, Shun-ichiro Izumi, Stanko S. Stojilkovic, and Andres Stutzin
- Subjects
endocrine system ,medicine.medical_specialty ,Fluorescence spectrometry ,chemistry.chemical_element ,Calcium ,Biology ,Gonadotropic cell ,Biochemistry ,Gonadotropin-Releasing Hormone ,Cytosol ,Desensitization (telecommunications) ,Pituitary Gland, Anterior ,Internal medicine ,medicine ,Animals ,Patch clamp ,Molecular Biology ,Cells, Cultured ,Membrane potential ,Voltage-dependent calcium channel ,Electric Conductivity ,Rats, Inbred Strains ,Cell Biology ,3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester ,Luteinizing Hormone ,Calcium Channel Blockers ,Rats ,Gonadotropin secretion ,Kinetics ,Endocrinology ,chemistry ,Potassium ,Female ,Calcium Channels ,hormones, hormone substitutes, and hormone antagonists - Abstract
Gonadotropin-releasing hormone (GnRH) stimulates calcium mobilization and influx in pituitary gonadotrophs, and agonist-induced calcium entry through voltage-sensitive channels (VSCC) is required for the maintenance of gonadotropin secretion. However, prolonged or frequent exposure to GnRH attenuates the extracellular Ca2+-dependent cytosolic Ca2+ signal and diminishes hormone secretion. Measurements of membrane Ca2+ currents revealed significant impairment of VSCC activity in gonadotrophs during desensitization by GnRH. VSSC were also inactivated in a calcium-dependent manner during exposure to high K+. Prolonged inactivation of such Ca2+ channels by high K+ reduced the calcium and secretory responses to GnRH and vice versa. The calcium-dependent inactivation of VSCC during GnRH action appears to be a primary factor in the onset of desensitization in pituitary gonadotrophs. This mechanism could also account for the development of agonist-induced refractoriness in other calcium-regulated target cells.
- Published
- 1989
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