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

Ishibashi, Masayoshi; Yamaji, Taiki

doi:10.1172/jci111208

Cited by 69 publications

(22 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…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: 68%

See 1 more Smart Citation

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.

View full text Add to dashboard Cite

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...

show abstract

Section: Introductionmentioning

confidence: 68%

“…Three GH-producing human pituitary adenomas were obtained at transsphenoidal surgery. The methods for preparing monolayer cells were essentially the same as described by Ishibashi and Yamaji (9,17). The tissue was minced into small pieces (less than 1 mm in diameter) and was treated with collagenase (0.2 mg/ml) and hyaluronidase (1 mg/ml).…”

Section: Methodsmentioning

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.

View full text Add to dashboard Cite

show abstract

“…In animals, dopamine has been found to decrease the secretion of GH by pituitary cells due to an increase in the release of somatostatin [57][58][59]. Similarly, it has been suggested that the increase in dopamine caused by stimulant administration in humans leads to a decrease in GH secretion [5] due to its effect on D2 dopamine receptors [60], which may have a direct inhibitory action on somatotropes [46].…”

Section: Stimulants and Growth Hormonementioning

confidence: 98%

“…D1 receptor stimulation, on the other hand, has been shown to increase prolactin levels [50,88,89]. Although not much research has been done into the effect of noradrenaline on prolactin release, it has been shown that noradrenaline causes prolactin suppression in both adenomatous and nonadenomatous pituitary cells [60], and that it decreases prolactin secretion via ovine pituitary cell adrenoreceptors [90]. However, unlike dopamine, noradrenaline is believed not to be a physiologically important prolactin-inhibiting factor [90].…”

Section: Stimulants and Prolactinmentioning

confidence: 99%

Stimulants and growth in children with attention-deficit/hyperactivity disorder

Negrao

Viljoen

2011

Medical Hypotheses

View full text Add to dashboard Cite

a b s t r a c tInitial suggestions that suppression of growth may be an intrinsic characteristic of attention-deficit/ hyperactivity disorder (ADHD) have now largely been disproven. Although controversy persists regarding the possible negative effect of adrenergic stimulants on growth in children with ADHD, the consensus that appears to be reached in the scientific literature is that stimulant usage may cause a manageable attenuation of growth in these children. Since it is known that stimulants increase the amount of dopamine and noradrenaline in the synapse, this writing suggests that these increases in dopamine and noradrenaline are responsible for the growth attenuation in these children. It appears that increased amounts of dopamine and noradrenaline have the ability to inhibit the secretion of growth hormone and growth-related hormones such as prolactin, thyroid hormones, sex hormones and insulin. Therefore, it would be reasonable to suggest that the increases in dopamine and noradrenaline caused by stimulant usage can disrupt the homeostasis of both growth hormone and growth-related hormones, generating the potential for the suppression of growth.

show abstract

“…For example, the dopamine agonist bromocriptine is used to treat hypersecretion of adrenocorticotrophic hormone (ACTH) in Nelson's disease (14) as well as hypersecretion of growth hormone (GH) in acromegaly (15). Moreover, dopamine was found to inhibit secretion of GH from human pituitary cells (16), and dopamine D2 receptors have been identified on thyroid stimulating hormone (TSH) adenoma's (17). Furthermore, stimulation of the D2 receptor leads to suppression of the luteinizing hormone (LH) by induction of the second messenger pituitary adenylate cyclaseactivating polypeptide (PACAP) in gonadotrophs (18).…”

Section: Introductionmentioning

confidence: 99%

Revealing the Neuroendocrine Response After Remoxipride Treatment Using Multi-Biomarker Discovery and Quantifying It by PK/PD Modeling

Brink

Wong

Gülave

et al. 2016

AAPS J

View full text Add to dashboard Cite

Abstract.To reveal unknown and potentially important mechanisms of drug action, multibiomarker discovery approaches are increasingly used. Time-course relationships between drug action and multi-biomarker profiles, however, are typically missing, while such relationships will provide increased insight in the underlying body processes. The aim of this study was to investigate the effect of the dopamine D2 antagonist remoxipride on the neuroendocrine system. Different doses of remoxipride (0, 0.7, 5.2, or 14 mg/kg) were administered to rats by intravenous infusion. Serial brain extracellular fluid (brainECF) and plasma samples were collected and analyzed for remoxipride pharmacokinetics (PK). Plasma samples were analyzed for concentrations of the eight pituitary-related hormones as a function of time. A Mann-Whitney test was used to identify the responding hormones, which were further analyzed by pharmacokinetic/ pharmacodynamic (PK/PD) modeling. A three-compartment PK model adequately described remoxipride PK in plasma and brainECF. Not only plasma PRL, but also adrenocorticotrophic hormone (ACTH) concentrations were increased, the latter especially at higher concentrations of remoxipride. Brain-derived neurotropic factor (BDNF), follicle stimulating hormone (FSH), growth hormone (GH), luteinizing hormone (LH), and thyroid stimulating hormones (TSH) did not respond to remoxipride at the tested doses, while oxytocin (OXT) measurements were below limit of quantification. Precursor pool models were linked to brainECF remoxipride PK by E max drug effect models, which could accurately describe the PRL and ACTH responses. To conclude, this study shows how a multi-biomarker identification approach combined with PK/PD modeling can reveal and quantify a neuroendocrine multi-biomarker response for single drug action.

show abstract

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

Cited by 69 publications

References 51 publications

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

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

Stimulants and growth in children with attention-deficit/hyperactivity disorder

Revealing the Neuroendocrine Response After Remoxipride Treatment Using Multi-Biomarker Discovery and Quantifying It by PK/PD Modeling

Contact Info

Product

Resources

About