Release of Growth Hormone from Purified Somatotrophs: Use of High K<sup>+</sup>and the Ionophore A23187 to Elucidate Interrelations among Ca<sup>++</sup>, Adenosine 3′,5′-Monophosphate, and Somatostatin*

Kraicer, Jacob; Spence, James W.

doi:10.1210/endo-108-2-651

Cited by 62 publications

(21 citation statements)

References 25 publications

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“…It is well known that elevated ex ternal level of potassium leads to an increase in the secre tion of anterior pituitary hormones [see ref. 27], This effect has been observed for tumoral [34] and normal pituitary cells [44,48].…”

Section: Effects Of Substances Known To Influence Gh Secretion On Thementioning

confidence: 83%

Electrophysiological Properties of Normal Somatotrophs in Culture

1983

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Normal rat pituitary cells were isolated and enriched to obtain a relatively pure population of growth hormone (GH) secreting cells by sedimentation at unit gravity and subsequently grown in culture. The electrophysiological properties of these cells were studied with intracellular recording techniques. 4–6-day-old cells did not show active electrical properties. At 7–9 days the cells were able to generate evoked responses (fast responses) which were blocked by inhibitors of calcium flux and prolonged with tetraethylammonium. The resting potential of these cells was sensitive to external local application of substances known to act on the release of GH. External elevated K⁺ induced a strong depolarizing response which was associated with an increase of membrane conductance. Somatostatin induced a hyperpolarizing response associated with a decrease of membrane conductance. It is suggested that the fast Ca²⁺-dependent responses and the slow variations of the resting potential induced by substances which modify hormone release may play an important role in the control of the secretory process of the presumably GH-secreting cells.

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Section: Effects Of Substances Known To Influence Gh Secretion On Thementioning

confidence: 83%

Electrophysiological Properties of Normal Somatotrophs in Culture

1983

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“…However, there appear to exist other mechanisms of somatostatin action for the following reasons: (i) It has been reported in rat GH4Cl cells and in purified rat somatotrophs that somatostatin reduces basal hormone release without a detectable change in cAMP (7,8,31). In addition, basal hormone release is independent of external Ca2l (8,32 …”

Section: Discussionmentioning

confidence: 99%

“…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).…”

mentioning

confidence: 99%

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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“…Human pancreatic-tumor growth hormone releasing factor (hGRF) has been demonstrated to be a potent, specific stimu lator o f growth hormone (GH) secretion in vivo and in vitro both in animals and in man [4,5). This peptide meeting certain criteria has been assumed to be similar or identical to hypotha lamic GRF [6][7][8]. The inhibition o f GRF-stimulated GH release by verapamil [9], cobalt [10], or inhibitors o f calcium-binding protein [II] suggests that Ca2* influx into the cell is a necessary Received: September 28, 1988 Accepted after revision: May 9, 1989 step for this release.…”

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confidence: 99%

Electrophysiological Responses of Rat Pituitary Cells in Somatotroph-Enriched Primary Culture to Human Growth-Hormone Releasing Factor

1989

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The in vitro effects of human growth hormone releasing factor (hGRF, 1–44) were studied in somatotroph-enriched cultures (75–85%) obtained from adult male rat pituitaries. Cells perifused with hGRF showed an up to 800% increase in growth hormone (GH) release over basal values in a dose-dependent manner. Calcium current Mockers (5 mM of Co²⁺, Ni²⁺ or Cd²⁺) completely inhibited this stimulating effect but sodium-free (choline) medium did not. Using a single-intracellular-electrode recording technique, it was found that hGRF induced a dose-dependent depolarizing response concomitant with a decrease in membrane resistance in 38% of the cells recorded (98 of 258 cells). The reversal potential of this response was close to –40 mV. This depolarizing response was recorded in both excitable and unexcitable cells with no marked difference. Co²⁺ and Ni²⁺ (5 mM) completely and reversibly inhibited the membrane response to hGRF. Application of hGRF and somatostatin (SRIF), a hormone that inhibits GH release, to the same cell cultures showed the existence of two subpopulations: one was responsive to both hGRF and SRIF (53%, n = 62), another was only responsive to SRIF (47%, n = 62). Human GRF did not affect prolactin release and did not modify the electrical properties of cells responding to dopamine and therefore considered as lactotrophs. These results suggest that (1) hGRF leads to an increase in growth hormone release and a modification of membrane electrical properties by means of an extracellular Ca²⁺-dependent pathway, and (2) according to their responses to SRIF and hGRF, there are at least two subpopulations of somatotrophs.

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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*

Cited by 62 publications

References 25 publications

Electrophysiological Properties of Normal Somatotrophs in Culture

Electrophysiological Properties of Normal Somatotrophs in Culture

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

Electrophysiological Responses of Rat Pituitary Cells in Somatotroph-Enriched Primary Culture to Human Growth-Hormone Releasing Factor

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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*

Cited by 62 publications

References 25 publications

Electrophysiological Properties of Normal Somatotrophs in Culture

Electrophysiological Properties of Normal Somatotrophs in Culture

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

Electrophysiological Responses of Rat Pituitary Cells in Somatotroph-Enriched Primary Culture to Human Growth-Hormone Releasing Factor

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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*