Abstract
Membrane electrical properties and the response to somatostatin were examined in dissociated human pituitary adenoma cells that secrete growth hormone (GH). Under current clamp condition with a patch electrode, the resting potential was -52.4 +/- 8.0 mV, and spontaneous action potentials were observed in 58% of the cells. Under voltage clamp condition an outward K+ current, a tetrodotoxin-sensitive Na+ current, and a Ca2+ current were observed. Cobalt ions suppressed the Ca2+ current. The threshold of Ca2+ current activation was about -60 mV. Somatostatin elicited a membrane hyperpolarization associated with increased membrane permeability in these cells. The reversal potential of somatostatin-induced hyperpolarization was -78.4 +/- 4.3 mV in 6 mM K+ medium and -97.2 +/- 6.4 mV in 3 mM K+ medium. These reversal potential values and a shift with the external K+ concentration indicated that membrane hyperpolarization was caused by increased permeability to K+. The hyperpolarized membrane potential induced by somatostatin was -63.6 +/- 5.9 mV in the standard medium. This level was subthreshold for Ca2+ and Na+ currents and was sufficient to inhibit spontaneous action potentials. Hormone secretion was significantly suppressed by somatostatin and cobalt ions. Therefore, we suggest that Ca2+ entering the cell through voltage-dependent channels are playing an important role for GH secretion and that somatostatin suppresses GH secretion by blocking Ca2+ currents. Finally, we discuss other possibilities for the inhibitory effect of somatostatin on GH secretion.
Full text
PDF![6198](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3bc/386467/5de688a2d27a/pnas00320-0454.png)
![6199](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3bc/386467/4a4e4cfc8879/pnas00320-0455.png)
![6200](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3bc/386467/45d136ffc46a/pnas00320-0456.png)
![6201](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3bc/386467/2114368377fe/pnas00320-0457.png)
![6202](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3bc/386467/3656dc8c9a3f/pnas00320-0458.png)
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Adams E. F., Brajkovich I. E., Mashiter K. Hormone secretion by dispersed cell cultures of human pituitary adenomas: effects of theophylline, thyrotropin-releasing hormone, somatostatin, and 2-bromo-alpha-ergocryptine. J Clin Endocrinol Metab. 1979 Jul;49(1):120–126. doi: 10.1210/jcem-49-1-120. [DOI] [PubMed] [Google Scholar]
- Bilezikjian L. M., Vale W. W. Stimulation of adenosine 3',5'-monophosphate production by growth hormone-releasing factor and its inhibition by somatostatin in anterior pituitary cells in vitro. Endocrinology. 1983 Nov;113(5):1726–1731. doi: 10.1210/endo-113-5-1726. [DOI] [PubMed] [Google Scholar]
- Cronin M. J., Rogol A. D., Myers G. A., Hewlett E. L. Pertussis toxin blocks the somatostatin-induced inhibition of growth hormone release and adenosine 3',5'-monophosphate accumulation. Endocrinology. 1983 Jul;113(1):209–215. doi: 10.1210/endo-113-1-209. [DOI] [PubMed] [Google Scholar]
- Dorflinger L. J., Schonbrunn A. Somatostatin inhibits basal and vasoactive intestinal peptide-stimulated hormone release by different mechanisms in GH pituitary cells. Endocrinology. 1983 Nov;113(5):1551–1558. doi: 10.1210/endo-113-5-1551. [DOI] [PubMed] [Google Scholar]
- Dorflinger L. J., Schonbrunn A. Somatostatin inhibits vasoactive intestinal peptide-stimulated cyclic adenosine monophosphate accumulation in GH pituitary cells. Endocrinology. 1983 Nov;113(5):1541–1550. doi: 10.1210/endo-113-5-1541. [DOI] [PubMed] [Google Scholar]
- Dufy B., Israel J. M., Zyzek E., Dufy-Barbe L., Guerin J., Fleury H., Vincent J. D. An electrophysiological study of cultured human pituitary cells. Mol Cell Endocrinol. 1982 Jul;27(2):179–190. doi: 10.1016/0303-7207(82)90107-1. [DOI] [PubMed] [Google Scholar]
- Hagiwara S., Ohmori H. Studies of calcium channels in rat clonal pituitary cells with patch electrode voltage clamp. J Physiol. 1982 Oct;331:231–252. doi: 10.1113/jphysiol.1982.sp014371. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hamill O. P., Marty A., Neher E., Sakmann B., Sigworth F. J. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch. 1981 Aug;391(2):85–100. doi: 10.1007/BF00656997. [DOI] [PubMed] [Google Scholar]
- Heisler S., Reisine T. D., Hook V. Y., Axelrod J. Somatostatin inhibits multireceptor stimulation of cyclic AMP formation and corticotropin secretion in mouse pituitary tumor cells. Proc Natl Acad Sci U S A. 1982 Nov;79(21):6502–6506. doi: 10.1073/pnas.79.21.6502. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ikuyama S., Nawata H., Kato K., Karashima T., Ibayashi H., Nakagaki H. Specific somatostatin receptors on human pituitary adenoma cell membranes. J Clin Endocrinol Metab. 1985 Oct;61(4):666–671. doi: 10.1210/jcem-61-4-666. [DOI] [PubMed] [Google Scholar]
- Ishibashi M., Yamaji T. Direct effects of catecholamines, thyrotropin-releasing hormone, and somatostatin on growth hormone and prolactin secretion from adenomatous and nonadenomatous human pituitary cells in culture. J Clin Invest. 1984 Jan;73(1):66–78. doi: 10.1172/JCI111208. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ishibashi M., Yamaji T. Effects of hypophysiotropic factors on growth hormone and prolactin secretion from somatotroph adenomas in culture. J Clin Endocrinol Metab. 1985 May;60(5):985–993. doi: 10.1210/jcem-60-5-985. [DOI] [PubMed] [Google Scholar]
- Israel J. M., Denef C., Vincent J. D. Electrophysiological properties of normal somatotrophs in culture. An intracellular study. Neuroendocrinology. 1983 Sep;37(3):193–199. doi: 10.1159/000123542. [DOI] [PubMed] [Google Scholar]
- Kraicer J., Spence J. W. Release of growth hormone from purified somatotrophs: use of high K+ and the ionophore A23187 to elucidate interrelations among Ca++, adenosine 3',5'-monophosphate, and somatostatin. Endocrinology. 1981 Feb;108(2):651–657. doi: 10.1210/endo-108-2-651. [DOI] [PubMed] [Google Scholar]
- Lamberts S. W., Verleun T., Oosterom R. The interrelationship between the effects of somatostatin and human pancreatic growth hormone-releasing factor on growth hormone release by cultured pituitary tumor cells from patients with acromegaly. J Clin Endocrinol Metab. 1984 Feb;58(2):250–254. doi: 10.1210/jcem-58-2-250. [DOI] [PubMed] [Google Scholar]
- Moyse E., Le Dafniet M., Epelbaum J., Pagesy P., Peillon F., Kordon C., Enjalbert A. Somatostatin receptors in human growth hormone and prolactin-secreting pituitary adenomas. J Clin Endocrinol Metab. 1985 Jul;61(1):98–103. doi: 10.1210/jcem-61-1-98. [DOI] [PubMed] [Google Scholar]
- Ozawa S., Kimura N. Membrane potential changes caused by thyrotropin-releasing hormone in the clonal GH3 cell and their relationship to secretion of pituitary hormone. Proc Natl Acad Sci U S A. 1979 Nov;76(11):6017–6020. doi: 10.1073/pnas.76.11.6017. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ozawa S., Saito T. Sodium and calcium action potentials in human anterior pituitary cells. Experientia. 1980 Oct 15;36(10):1235–1236. doi: 10.1007/BF01976149. [DOI] [PubMed] [Google Scholar]
- Ozawa S. TRH-induced membrane hyperpolarization in rat clonal anterior pituitary cells. Am J Physiol. 1985 Jan;248(1 Pt 1):E64–E69. doi: 10.1152/ajpendo.1985.248.1.E64. [DOI] [PubMed] [Google Scholar]
- Pace C. S., Tarvin J. T. Somatostatin: mechanism of action in pancreatic islet beta-cells. Diabetes. 1981 Oct;30(10):836–842. doi: 10.2337/diab.30.10.836. [DOI] [PubMed] [Google Scholar]
- Reubi J. C., Landolt A. M. High density of somatostatin receptors in pituitary tumors from acromegalic patients. J Clin Endocrinol Metab. 1984 Dec;59(6):1148–1151. doi: 10.1210/jcem-59-6-1148. [DOI] [PubMed] [Google Scholar]
- Richardson U. I., Schonbrunn A. Inhibition of adrenocorticotropin secretion by somatostatin in pituitary cells in culture. Endocrinology. 1981 Jan;108(1):281–290. doi: 10.1210/endo-108-1-281. [DOI] [PubMed] [Google Scholar]
- Schlegel W., Wuarin F., Wollheim C. B., Zahnd G. R. Somatostatin lowers the cytosolic free Ca2+ concentration in clonal rat pituitary cells (GH3 cells). Cell Calcium. 1984 Jun;5(3):223–236. doi: 10.1016/0143-4160(84)90038-1. [DOI] [PubMed] [Google Scholar]
- Schofield J. G., Bicknell R. J. Effects of somatostatin and verapamil on growth hormone release and 45Ca fluxes. Mol Cell Endocrinol. 1978 Jan;9(3):255–268. doi: 10.1016/0303-7207(78)90068-0. [DOI] [PubMed] [Google Scholar]
- Spada A., Sartorio A., Bassetti M., Pezzo G., Giannattasio G. In vitro effect of dopamine on growth hormone (GH) release from human GH-secreting pituitary adenomas. J Clin Endocrinol Metab. 1982 Oct;55(4):734–740. doi: 10.1210/jcem-55-4-734. [DOI] [PubMed] [Google Scholar]
- Spada A., Vallar L., Giannattasio G. Presence of an adenylate cyclase dually regulated by somatostatin and human pancreatic growth hormone (GH)-releasing factor in GH-secreting cells. Endocrinology. 1984 Sep;115(3):1203–1209. doi: 10.1210/endo-115-3-1203. [DOI] [PubMed] [Google Scholar]
- Tan K. N., Tashjian A. H., Jr Voltage-dependent calcium channels in pituitary cells in culture. II. Participation in thyrotropin-releasing hormone action on prolactin release. J Biol Chem. 1984 Jan 10;259(1):427–434. [PubMed] [Google Scholar]
- Vale W., Rivier C., Brazeau P., Guillemin R. Effects of somatostatin on the secretion of thyrotropin and prolactin. Endocrinology. 1974 Oct;95(4):968–977. doi: 10.1210/endo-95-4-968. [DOI] [PubMed] [Google Scholar]
- Webb C. B., Thominet J. L., Frohman L. A. Ectopic growth hormone releasing factor stimulates growth hormone release from human somatotroph adenomas in vitro. J Clin Endocrinol Metab. 1983 Feb;56(2):417–419. doi: 10.1210/jcem-56-2-417. [DOI] [PubMed] [Google Scholar]
- Yamashita N., Takuwa Y., Ogata E. Growth hormone-releasing factor reduces voltage-gated Ca2+ channel current in rat GH3 cells. J Membr Biol. 1985;87(3):241–247. doi: 10.1007/BF01871224. [DOI] [PubMed] [Google Scholar]