Estradiol-modified prolactin secretion independently of action potentials and Ca²⁺ and blockade of outward potassium currents in GH₃ cells

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• 作者：Manuel Sánchez ; Lorena Suárez…
• 关键词：Adenohypophysis ; Estradiol ; Ca2+ ; channels ; Potassium channels ; Voltage ; and Ca2+ ; activated potassium channel ; GH3 cells ; Prolactin
• 刊名：Naunyn-Schmiedeberg's Archives of Pharmacology
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：390
• 期：1
• 页码：95-104
• 全文大小：
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Pharmacology/Toxicology; Neurosciences;
• 出版者：Springer Berlin Heidelberg
• ISSN：1432-1912
• 卷排序：390

文摘

Estrogens facilitate prolactin (PRL) secretion acting on pituitary cells. In GH₃ cells, estradiol induces acute action potentials and oscillations of intracellular Ca2+ associated with the secretagogue function. Estradiol modulates several ion channels which may affect the action potential rate and the release of PRL in lactotroph cells, which might depend on its concentration. The aims were to characterize the acute effect of supraphysiological concentrations of estradiol on Ca2+ and noninactivating K+ currents and measure the effect on the spontaneous action potentials and PRL release in the somatolactotroph cell line, GH₃. Electrophysiological studies were carried out by voltage- and current-clamp techniques and ELISA determination of PRL secretion. Pharmacological concentrations of estradiol (above 1 μM), without a latency period, blocked Ca2+ channels and noninactivating K+ currents, including the large-conductance voltage- and Ca2+-activated K+ channels (BK), studied in whole-cell nystatin perforated and in excided inside-out patches of GH₃ and CHO cells, transiently transfected with the human α-pore forming subunit of BK. The effect on BK was contrary to the agonist effect associated with the regulatory β₁-subunits of the BK, which GH₃ cells lack, but its transient transfection did not modify the noninactivating current blockade, suggesting a different mechanism of regulation. Estradiol, at the same concentration range, acutely decreased the frequency of action potentials, an expected effect as consequence of the Ca2+ channel blockade. Despite this, PRL secretion initially increased, followed by a decrease in long-term incubations. This suggests that, in GH₃ cells, supraphysiological concentrations of estradiol modulating PRL secretion are partially independent of extracellular Ca2+ influx.