Hormone Secretion by Dispersed Cell Cultures of Human Pituitary Adenomas: Effects of Theophylline, Thyrotropin-Releasing Hormone, Somatostatin, and 2-Bromo-α-Ergocryptine*

Adams, Eric F.; Brajkovich, Imperia; Mashiter, Κ.

doi:10.1210/jcem-49-1-120

Cited by 87 publications

(43 citation statements)

References 10 publications

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“…This finding was subsequently confirmed by other investigators (14)(15)(16)(17)(18). We have also demonstrated by this experimental approach that thyrotropin-releasing hormone These results indicate that dopaminergic agonists and TRH affect GH and PRL secretion in these patients by their direct action on pituitary adenoma, and further suggest that a possible alteration in cellular membrane receptors of the pituitary adenoma of acromegalic patients may be responsible for anomalous GH responses.…”

supporting

confidence: 87%

Direct effects of catecholamines, thyrotropin-releasing hormone, and somatostatin on growth hormone and prolactin secretion from adenomatous and nonadenomatous human pituitary cells in culture.

Ishibashi¹,

Yamaji²

1984

J. Clin. Invest.

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A bstract. To determine the mechanism and the site of action of catecholamines as well as hormones including thyrotropin-releasing hormone (TRH)' and somatostatin on pituitary hormone release in patients with acromegaly and in normal subjects, the effects of these substances on growth hormone (GH) and prolactin (PRL) secretion from adenomatous and nonadenomatous human pituitary cells in culture were examined. When dopamine (0.01-0.1 tM) or bromocriptine (0.01-0.1 tM) was added to the culture media, a significant inhibition of GH

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supporting

confidence: 87%

Direct effects of catecholamines, thyrotropin-releasing hormone, and somatostatin on growth hormone and prolactin secretion from adenomatous and nonadenomatous human pituitary cells in culture.

Ishibashi¹,

Yamaji²

1984

J. Clin. Invest.

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“…These results are consistent with the results for the dopamine action in rats [16,22]. However, even 10-5 M dopamine did not alter these two parameters in pituitary cells from some other patients (cases 5 and 6).…”

Section: Discussionsupporting

confidence: 91%

“…This is quite different from the methods used in previous studies [16][17][18][19][20][21]. The most important characteristic of this assay is that it is able to quantify hormone secretion from single endocrine cells in culture, which is difficult for a combination of conventional culture experiments and radioimmunoassay.…”

Section: Discussionmentioning

confidence: 90%

Dopamine Responsiveness of Human Prolactinoma Cells as Determined by the Reverse Hemolytic Plaque Assay.

Kojima

Ai²,

Kuwana

et al. 1995

Endocr J

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Abstract. The responsiveness in vivo to dopamine of prolactin (PRL) secretion in patients with prolactinoma was compared with that in vitro of single cells obtained from the same prolactinomas by surgical operations. Six patients with prolactinoma showing various degrees of hyperprolactinemia were challenged by bromocriptine suppression test (2.5 mg, peroral) before operation. Bromocriptine administration caused a decrease in the serum PRL concentration ranging 24-95% and there was no correlation between the basal PRL level and bromocriptine-induced inhibition. Monodispersed pituitary cells obtained from the prolactinomas by operation were subjected to a reverse hemolytic plaque assay for PRL to determine PRL secretion at the single cell level under basal conditions as well as in response to dopamine. The percentage of plaque-forming cells under basal conditions ranged 15-55% among the prolactinomas.The percentage of plaque-forming cells and plaque area were decreased in a dosedependent manner by 10-'-10-5 M dopamine for the pituitary cells obtained from some adenomas but not for those from other adenomas. When the inhibition rates in vitro due to 10-5 M dopamine in these two parameters were compared with the inhibition rate in vivo in the serum PRL concentration due to bromocriptine, it was found that there was a significant correlation between them. These results show that the reverse hemolytic plaque assay can be used to determine in vitro responsiveness to dopamine of PRL secretion from single prolactinoma cells. We conclude that 1) the relative abundance of PRLsecreting cells varies among prolactinomas; and 2) there is a correlation between in vivo and in vitro responsiveness of prolactinoma cells to dopaminergic inhibition.

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“…In analogy, a similar mechanism of somatostatin may exist in the pituitary. For the investigation of the mechanism of somatostatin action in the pituitary, human GH-producing pituitary tumor cells are useful because the presence of somatostatin receptors in the cell membrane has been demonstrated (12)(13)(14) and the inhibition of GH secretion by somatostatin has been reported (15)(16)(17)(18)(19). In the present study we investigated the response of the membrane potential to somatostatin in dissociated human pituitary adenomas that secreted GH, and we found that somatostatin increased the K+ conductance.…”

Section: Introductionmentioning

confidence: 69%

Hyperpolarization of the membrane potential caused by somatostatin in dissociated human pituitary adenoma cells that secrete growth hormone.

Yamashita¹,

Shibuya²,

Ogata³

1986

Proc. Natl. Acad. Sci. U.S.A.

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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 damp condition an outward K+ current, a tetrodotoxinsensitive 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 KV.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 Ca21 currents. Finally, we discuss other possibilities for the inhibitory effect of somatostatin on GH secretion.Somatostatin (somatotropin release-inhibiting factor, SRIF) is a potent inhibitor of growth hormone (GH) secretion. It also inhibits the secretion of other pituitary hormones (1, 2) and extrapituitary hormones (3). GH secretion is known to be regulated by the level of intracellular cyclic AMP (cAMP), which is raised by a stimulatory hormone, such as GHreleasing factor (4). It has been claimed that somatostatin exerts its inhibitory action through the reduction of cAMP production (5-7).Ca2l is another important factor that controls GH secretion from the anterior pituitary. It has been shown that Ca2l is required for GH release evoked by high concentrations of extracellular K+ (8) and GH-releasing factor (4, 9). Various anterior pituitary cell lines have b*,n shown to have action potentials that are dependent on Ca2l or Na+ (10). The influx of Ca2l is postulated to be controlled at least partly by the action potential. The membrane-signal transduction mechanism for somatostatin action has not yet been fully clarified in the pituitary. In the rat pancreas islet it has been reported that somatostatin activates a K+ conductance and inhibits glucose-induced insulin release (11). In analogy, a similar mechanism of somatostatin may exist in the pituitary. For the investigation of the mechanism of somatostatin action in the pituitary, human GH-producing pituitary tumor cells are useful because the presence of somatostatin receptors in the cell membrane has been demonstrated (12...

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Hormone Secretion by Dispersed Cell Cultures of Human Pituitary Adenomas: Effects of Theophylline, Thyrotropin-Releasing Hormone, Somatostatin, and 2-Bromo-α-Ergocryptine*

Cited by 87 publications

References 10 publications

Direct effects of catecholamines, thyrotropin-releasing hormone, and somatostatin on growth hormone and prolactin secretion from adenomatous and nonadenomatous human pituitary cells in culture.

Direct effects of catecholamines, thyrotropin-releasing hormone, and somatostatin on growth hormone and prolactin secretion from adenomatous and nonadenomatous human pituitary cells in culture.

Dopamine Responsiveness of Human Prolactinoma Cells as Determined by the Reverse Hemolytic Plaque Assay.

Hyperpolarization of the membrane potential caused by somatostatin in dissociated human pituitary adenoma cells that secrete growth hormone.

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