Effect of Ca<sup>2+</sup> and cAMP on capacitance-measured  hormone secretion in human GH-secreting adenoma cells

Takei, Tomoyuki; Yasufuku‐Takano, Junko; Takano, Koji; Fujita, Toshiro; Yamashita, Naohide

doi:10.1152/ajpendo.1998.275.4.e649

Cited by 6 publications

(8 citation statements)

References 26 publications

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“…This is in contrast to the action of GHRH on Na + , Ca 2+ and non-selective cation currents in pituitary cells. 7,34,[37][38][39][40] Moreover, these results differ from previous reports that cAMP or PKA inhibits the I A current in neurons, 41 increases the I K current in smooth muscle cells 31 and reduces expression of Kv1.1 channels in glioma cells. 42 This is also the first time that the cAMP/PKA system has been shown to be not directly involved in an action of GHRH on somatotropes.…”

Section: Effects Of Ghrh On K + Currentscontrasting

confidence: 99%

“…The GHRH receptor is believed to be linked to the G s protein and adenylyl cyclase, which mediates the effect of GHRH on Ca 2+ , Na + and non-selective cation currents. [34][35][36][37][38] Here, we have studied whether cAMP and cAMP-dependent PKA are involved in the K + current response to GHRH. We have targeted the cAMP/PKA system at several intracellular signalling steps using a cAMP antagonist (Rp-cAMP) or analogue (8-bromo-cAMP) and specific PKA inhibitors (H 89 and PKI).…”

Section: Effects Of Ghrh On K + Currentsmentioning

confidence: 99%

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Diverse intracellular signalling systems used by growth hormone‐releasing hormone in regulating voltage‐gated Ca²⁺ or K⁺ channels in pituitary somatotropes

Chen¹,

Xu²,

Clarke³

et al. 2000

Immunol Cell Biol

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IntroductionGrowth hormone-releasing hormone (GHRH) has been shown to stimulate GH secretion in several species since it was identified, more than a decade ago.1,2 It is generally accepted that exocytosis of growth hormone (GH) from somatotropes is regulated by intracellular free Ca 2+ concentration ([Ca 2+ ]i). Growth hormone-releasing hormone increases [Ca 2+ ]i in pituitary somatotropes, an effect that is totally abolished by using extracellular Ca 2+ -free solution or by the blockade of Ca 2+ channels. [3][4][5] The large Ca 2+ concentration gradient across the cell membrane allows a significant increase in [Ca 2+ ]i when membrane Ca 2+ channels are opened. It has been shown that GHRH depolarizes the membrane potential of pituitary somatotropes and increases the frequency of action potentials. 6,7 The majority of Ca 2+ channels in the membranes of somatotropes are voltage-gated 8 and depolarization or the generation of action potential by GHRH would be expected to trigger an influx of Ca 2+ . Because most of the ionic currents across the membrane at resting potential are carried by K + , the transmembrane K + channels are thought to play an important role in GHRH-induced depolarization. 7,9-11 Growth hormone-releasing hormone indeed decreases membrane voltage-gated K + currents. 12,13 The effect of GHRH on the membrane ion channels is most probably mediated by second messenger systems. This is because electrophysiological responses to GHRH cannot be observed with classical whole cell recording, but do occur during microelectrode intracellular recording, 6 on-cell patch recording 14 or nystatin-perforated recording, 7,9,12 when intracellular macromolecular second messenger systems remain undisturbed. In order to clarify the signalling systems used by GHRH on voltage-gated Ca 2+ and K + channels, patch-clamp techniques were used to record the channel responses to GHRH in primary cultured ovine and human somatotropes. Materials and Methods Cell preparationSheep pituitaries were obtained from a local abattoir and then subjected to collagenase/pancreatin treatment to liberate cells as described previously.15 Briefly, whole pituitaries were divested of encapsulating tissue and the neurohypophysis and pituitary stalk tissue. The anterior pituitaries were then minced and placed into 0.15% collagenase/calcium-free HEPES-buffered solution (HBS). The tissue fragments were gently agitated for 20-30 min at 37°C, then similarly incubated in pancreatin solution for a further 20 min, followed by a gentle trituration in DNase containing 0.5 mg/mL

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Section: Effects Of Ghrh On K + Currentscontrasting

confidence: 99%

Section: Effects Of Ghrh On K + Currentsmentioning

confidence: 99%

Diverse intracellular signalling systems used by growth hormone‐releasing hormone in regulating voltage‐gated Ca²⁺ or K⁺ channels in pituitary somatotropes

Chen¹,

Xu²,

Clarke³

et al. 2000

Immunol Cell Biol

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“…In somatotropes, we and others have previously showed that the K ϩ , Na ϩ , and Ca 2ϩ channels were modified by GHRH, GHRP, and somatostatin (17,44,45), and both PKA-cAMP and PKC systems were involved in the intracellular signal transduction employed by these peptides (44,49). We therefore tried to elucidate the possible intracellular signaling pathways by which orexin-A induced the increase in the L current in ovine somatotropes.…”

Section: Discussionmentioning

confidence: 99%

“…These blockers have been previously successfully employed to examine the effect of a GHRH-induced change in the Ca 2ϩ and K ϩ currents in somatotropes (43)(44)(45). The specific blocking effects of H89 and other inhibitors on the PKA signaling pathway have been examined by us in a recent study of the effect of GHRP-2 on inward rectifying K ϩ currents (Xu, R., unpublished data) and by others (44).…”

Section: Involvement Of the Pka-camp System In The Ca 2ϩ Current Respmentioning

confidence: 99%

Orexin-A Augments Voltage-Gated Ca2+ Currents and Synergistically Increases Growth Hormone (GH) Secretion with GH-Releasing Hormone in Primary Cultured Ovine Somatotropes

Wang²,

Yan³

et al. 2002

Endocrinology

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Orexins are recently discovered neuropeptides that play an important role in the regulation of hormone secretion, and their receptors have been recently demonstrated in the pituitary. The effects of orexin-A on voltage-gated Ca2+ currents and GH release in primary cultured ovine somatotropes were examined. The expression of orexin-1 receptor was demonstrated by RT-PCR in ovine somatotropes, from which Ca2+ currents were also isolated as L, T, and N currents. Application of orexin-A (100 nM) significantly and reversibly increased only the L current, and coadministration of orexin-A and GHRH (10 nM) showed an additive effect on this current, but no effect of orexin-A was observed on either T or N current. Furthermore, the orexin-A-induced increase in the L current was completely abolished by the inhibition of protein kinase C (PKC) activity using calphostin C (100 nM), phorbal 12,13-dibutyrate pretreatment (0.5 micro M) for 16 h or specific PKC inhibitory peptide PKC(19-36) (1 mM). However, the increase in L current by orexin-A was sustained when cells were preincubated with a specific protein kinase A blocker H89 (1 micro M) or a specific intracellular Ca2+ store depleting reagent thapsigargin (1 micro M). Finally, orexin-A alone did not significantly increase GH release, but coadministration of orexin-A and GHRH showed a synergistic effect on GH secretion in vitro. Our results therefore suggest that orexin-A may play an important role in regulating GHRH-stimulated GH secretion through the enhancement of the L-type Ca2+ current and the PKC-mediated signaling pathway in ovine somatotropes.

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“…In our study, eGFP (GH) release in response to GHRH stimulus was greater in slices from male pituitary glands than in slices from female glands. Given the higher proportion of GH cells responsive to GHRH in males, simple summation of the ensuing calcium-dependent exocytotic responses would account for the observed differences in GH secretion (32)(33)(34). Finally, a remarkable feature of GH responses in males was that a single application of GHRH could trigger repetitive waves of calcium spiking activity that persisted well beyond the cessation of GHRH exposure.…”

Section: Gh Cells In An Intact Network Show Sex-specific Organized Pamentioning

confidence: 99%

Pituitary growth hormone network responses are sexually dimorphic and regulated by gonadal steroids in adulthood

Sánchez-Cárdenas

Fontanaud

et al. 2010

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

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There are well-recognized sex differences in many pituitary endocrine axes, usually thought to be generated by gonadal steroid imprinting of the neuroendocrine hypothalamus. However, the recognition that growth hormone (GH) cells are arranged in functionally organized networks raises the possibility that the responses of the network are different in males and females. We studied this by directly monitoring the calcium responses to an identical GH-releasing hormone (GHRH) stimulus in populations of individual GH cells in slices taken from male and female murine GH-eGFP pituitary glands. We found that the GH cell network responses are sexually dimorphic, with a higher proportion of responding cells in males than in females, correlated with greater GH release from male slices. Repetitive waves of calcium spiking activity were triggered by GHRH in some males, but were never observed in females. This was not due to a permanent difference in the network architecture between male and female mice; rather, the sex difference in the proportions of GH cells responding to GHRH were switched by postpubertal gonadectomy and reversed with hormone replacements, suggesting that the network responses are dynamically regulated in adulthood by gonadal steroids. Thus, the pituitary gland contributes to the sexually dimorphic patterns of GH secretion that play an important role in differences in growth and metabolism between the sexes. sex hormones | body growth | calcium signaling | systems biology I n most species, males and females display a marked phenotypic divergence in body size, with increased growth rate and body mass being a predominantly masculine trait. Furthermore, in all species examined to date, the growth hormone (GH) axis demonstrates sex-specific differences in hormone contents, secretory outputs, and secretory patterns (1) and their effects on gene expression (2-4). The secretion of GH is controlled by hypothalamic GH-releasing hormone (GHRH) and somatostatin, and there is good evidence for sex-specific imprinting on hypothalamic hypophysiotropic neurons exerted by gonadal steroid exposure early in life (5), with ongoing effects during puberty (6). This has led to the conclusion that the sexually dimorphic control of GH patterns reflects sex differences in GHRH and somatostatin inputs to the pituitary gland. Acute changes in gonadal steroid environment drastically alter the patterns of GH pulsatility in adulthood (7,8); however, although they receive sexually dimorphic inputs (9, 10), GHRH neurons do not display sex-specific electrical characteristics (9, 11). We have previously shown that GH cells in the male mouse pituitary gland form an extensive homotypic cell network with an architecture that exhibits marked plasticity during sexual maturation and that can be altered by gonadectomy (12). Thus, it was important to determine whether male and female pituitary glands would show different responses to the same stimulus in the absence of any hypothalamic influence. To explore this, we assessed the functional activit...

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Effect of Ca²⁺ and cAMP on capacitance-measured hormone secretion in human GH-secreting adenoma cells

Cited by 6 publications

References 26 publications

Diverse intracellular signalling systems used by growth hormone‐releasing hormone in regulating voltage‐gated Ca²⁺ or K⁺ channels in pituitary somatotropes

Diverse intracellular signalling systems used by growth hormone‐releasing hormone in regulating voltage‐gated Ca²⁺ or K⁺ channels in pituitary somatotropes

Orexin-A Augments Voltage-Gated Ca2+ Currents and Synergistically Increases Growth Hormone (GH) Secretion with GH-Releasing Hormone in Primary Cultured Ovine Somatotropes

Pituitary growth hormone network responses are sexually dimorphic and regulated by gonadal steroids in adulthood

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Effect of Ca2+ and cAMP on capacitance-measured hormone secretion in human GH-secreting adenoma cells

Cited by 6 publications

References 26 publications

Diverse intracellular signalling systems used by growth hormone‐releasing hormone in regulating voltage‐gated Ca2+ or K+ channels in pituitary somatotropes

Diverse intracellular signalling systems used by growth hormone‐releasing hormone in regulating voltage‐gated Ca2+ or K+ channels in pituitary somatotropes

Orexin-A Augments Voltage-Gated Ca2+ Currents and Synergistically Increases Growth Hormone (GH) Secretion with GH-Releasing Hormone in Primary Cultured Ovine Somatotropes

Pituitary growth hormone network responses are sexually dimorphic and regulated by gonadal steroids in adulthood

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Effect of Ca²⁺ and cAMP on capacitance-measured hormone secretion in human GH-secreting adenoma cells

Diverse intracellular signalling systems used by growth hormone‐releasing hormone in regulating voltage‐gated Ca²⁺ or K⁺ channels in pituitary somatotropes

Diverse intracellular signalling systems used by growth hormone‐releasing hormone in regulating voltage‐gated Ca²⁺ or K⁺ channels in pituitary somatotropes