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Titolo:
Heterozygous gsp mutation renders ion channels of human somatotroph adenoma cells unresponsive to growth hormone-releasing hormone
Autore:
Yasufuku-Takano, J; Takano, K; Takei, T; Fukumoto, S; Teramoto, A; Takakura, K; Yamashita, N; Fujita, T;
Indirizzi:
Univ Tokyo, Sch Med, Dept Internal Med 4, Bunkyo Ku, Tokyo 1128688, Japan Univ Tokyo Tokyo Japan 1128688 al Med 4, Bunkyo Ku, Tokyo 1128688, Japan Nippon Med Sch, Dept Neurosurg, Bunkyo Ku, Tokyo 1138603, Japan Nippon MedSch Tokyo Japan 1138603 surg, Bunkyo Ku, Tokyo 1138603, Japan Tokyo Womens Med Coll, Neurol Inst, Shinjuku Ku, Tokyo 1620054, Japan Tokyo Womens Med Coll Tokyo Japan 1620054 njuku Ku, Tokyo 1620054, Japan
Titolo Testata:
ENDOCRINOLOGY
fascicolo: 5, volume: 140, anno: 1999,
pagine: 2018 - 2026
SICI:
0013-7227(199905)140:5<2018:HGMRIC>2.0.ZU;2-8
Fonte:
ISI
Lingua:
ENG
Soggetto:
ANTERIOR-PITUITARY-CELLS; BIOCHEMICAL CHARACTERISTICS; INTRACELLULAR CALCIUM; ACROMEGALIC PATIENTS; SOMATOSTATIN; STIMULATION; INHIBITION; SECRETION; CURRENTS; INVITRO;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
28
Recensione:
Indirizzi per estratti:
Indirizzo: Yasufuku-Takano, J UnivoTokyo, Sch Med, Dept Internal Med 4, Bunkyo Ku, 3-28-6 Mejirodai, Toky Univ Tokyo 3-28-6 Mejirodai Tokyo Japan 1128688 , Toky
Citazione:
J. Yasufuku-Takano et al., "Heterozygous gsp mutation renders ion channels of human somatotroph adenoma cells unresponsive to growth hormone-releasing hormone", ENDOCRINOL, 140(5), 1999, pp. 2018-2026

Abstract

Ionic mechanisms play an important role in the regulation of hormone secretion. The GHRH-induced GH release by human GH-secreting cells is transmitted through protein kinase A (PKA), which activates nonselective cation current (NSCC) and induces membrane depolarization, intracellular Ca2+ increase,and GH secretion. To evaluate whether ionic mechanisms have pathophysiological significance in GH oversecretion of GH-secreting pituitary adenomas, we examined four adenomas with constitutively active Gsa mutation (gsp mutation) and compared with three gsp-negative adenomas. Ln primary-cultured cells of gsp-positive adenomas, GHRP did not increase the NSCC under voltage-clamp experiments. Detailed examination showed that NSCC was maximally activated at the basal level and application of GHRH did not increase the current in these adenomas. Furthermore, by using single-cell RT-PCR method, we demonstrated for the first time at the single cell level that gsp mutation isheterozygous in GH-secreting pituitary adenomas. These indicate that heterozygous gsp mutation fully activates NSCC at the basal level, which may account for the GH oversecretion in gsp-positive GH-secreting pituitary adenomas.

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Documento generato il 02/12/20 alle ore 15:34:16