Evidence that Stimulation of Thyrotropin and Prolactin Secretion by Thyrotropin-Releasing Hormone Occur via Different Calcium-Mediated Mechanisms: Studies with Verapamil*

Geras, Elizabeth; Rebecchi, Mario J.; Gershengorn, Marvin C.

doi:10.1210/endo-110-3-901

Cited by 78 publications

(15 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Finally, it must be pointed out that mobilization of intracellular Ca +2 as a mechanism of secretagogue action is not without precedent, as it has been recently shown to mediate TRH-induced PRL release from normal pituitary cells and clonal pituitary cell lines (40)(41)(42). Examination of the mechanism by which PGE 2 may mobilize intraterminal Ca +2 in the ME warrants further investigation.…”

Section: Discussionmentioning

confidence: 99%

Prostaglandin E₂-Induced Luteinizing Hormone- Releasing Hormone Release Involves Mobilization of Intracellular Ca⁺²*

Ojeda

Negro‐Vilar

1985

Endocrinology

View full text Add to dashboard Cite

The present in vitro experiments were performed to examine the involvement of Ca+2 in the mechanism by which prostaglandin E2 (PGE2) induces LHRH release from the median eminence (ME) of the hypothalamus. Stepwise decreases in the Ca+2 concentration of the incubation medium reduced the LHRH response to PGE2. Nevertheless, neither complete omission of Ca+2 (residual Ca+2 concentration, 3.5 microM) nor chelation of residual Ca+2 with EGTA prevented the stimulatory effect of the PG, suggesting that a significant portion of the PGE2 effect on LHRH release is independent of extracellular Ca+2. Blockade of Ca+2 influx with verapamil, a Ca+2 entry blocker, demonstrated that this component of the PGE2 effect is completely independent of inward Ca+2 movement. Depletion of intraterminal Ca+2 stores by exposure of the MEs to the Ca+2 ionophore A23187 in medium without Ca+2 containing EGTA almost completely obliterated the subsequent LHRH response to PGE2, indicating that normal intraterminal Ca+2 levels are important for the PGE2 effect to occur. Preloading the ME terminals with 45Ca+2 and subsequent stimulation with PGE2 demonstrated that even in the absence of extracellular Ca+2, PGE2 stimulates Ca+2 efflux from the terminals, and this Ca+2 movement occurs temporarily associated with LHRH release. Depolarization of ME terminals with 56 mM K+ in the presence of normal Ca+2 concentration resulted in massive efflux of 45Ca+2 and a greater LHRH response than that produced by PGE2, suggesting that the effect of PGE2 is not the consequence of a nonspecific general depolarization of ME nerve terminals. Thus, although a full LHRH response to (exogenous) PGE2 necessitates normal extraterminal Ca+2 concentrations, the results indicate that translocation of Ca+2 from intracellular stores is an event involved in the mechanism by which PGE2 releases LHRH.

show abstract

Section: Discussionmentioning

confidence: 99%

Prostaglandin E₂-Induced Luteinizing Hormone- Releasing Hormone Release Involves Mobilization of Intracellular Ca⁺²*

Ojeda

Negro‐Vilar

1985

Endocrinology

View full text Add to dashboard Cite

show abstract

“…In vitro studies have demonstrated that calcium ions are essential for release of anterior pituitary hormone (Vale et al, 1967) and that the calcium antagonist verapamil inhibits the release of hormones from the pituitary in response to hypothalamic stimulatory releasing factors (Geras et al, 1982).…”

Section: Introductionmentioning

confidence: 99%

The effect of nicardipine on pituitary hormone release in normal volunteers.

Isles¹,

Baty²,

Dow³

1985

Brit J Clinical Pharma

View full text Add to dashboard Cite

Summary 1 In a double-blind, placebo-controlled, randomised, cross-over study of six healthy male subjects, the effect of nicardipine (5 mg h-1 for 3 h) on basal and stimulated pituitary hormone release was examined. 2 Statistically significant differences between nicardipine and placebo were seen occasionally for follicle-stimulating hormone, luteinising hormone and prolactin, but not for thyroidstimulating hormone. These differences were always within the between-batch coefficient of variation of the assay. 3 The overall differences in both basal and stimulated results for all four pituitary hormones were not statistically significantly different. 4 It is concluded, therefore, that nicardipine has no significant effect on either basal or stimulated pituitary hormone release in healthy male subjects.

show abstract

“…The fact that, at the concentrations tested here, the three drugs did not modify (for verapamil and nifedipine) or slightly reduce (for diltiazem) the TSH response to TRH strengthens this hypothesis. It must be pointed out that, in other experimental models, similar concentrations of verapa mil partially inhibited TRH-stimulated TSH release but not TRH-stimulated prolactin secretion from cultured tumoral pitu itary cells [17] or abolished TRH-induced TSH secretion from dispersed normal pituitary cells [20]. The fact that in our study, verapamil and nifedipine, at the concentrations tested here, did not modify TRH-stimulated TSH release may come from the different conditions and models used: perifusion of pituitary fragments instead of long-term incubation of normal or tumoral pituitary cells.…”

Section: Discussionmentioning

confidence: 87%

“…Extra cellular signals that elicit a secretory response are doing so by increasing cytoplasmic Ca2+ trough an influx of extracellular Ca2+ an d /o r by mobilization of intracellular stores. The thyro tropic effect of TRH is supposed to involve both phenomena (16)(17)(18) and this dual mechanism serves to augment further TSH secretion. By choosing a Co2+concentration (3 mM) that, under our conditions, did not significantly modify the TSH re sponse to TRH, we observed a complete reversal of the effect of PS4, suggesting that the PS4 effect is largely dependent upon an influx of extracellular Ca2 + .…”

Section: Discussionmentioning

confidence: 99%

A Prepro-TRH Connecting Peptide (Prepro-TRH 160–169) Potentiates TRH-Induced TSH Release from Rat Perifused Pituitaries by Stimulating Dihydropyridine- and Omega-Conotoxin-Sensitive Ca<sup>2+</sup> Channels

Roussel

Hollande²,

Bulant³

et al. 1991

Neuroendocrinology

View full text Add to dashboard Cite

The stimulation of TSH secretion by TRH involves the phosphatidylinositol second messenger pathway via activation of phospholipase C. This effect is mediated by a GTP-binding protein and leads to a mobilization of intracellular Ca²⁺ stores and an activation of protein kinase C. However, TRH stimulation also results in an influx of extracellular Ca²⁺. Since we have previously demonstrated that a non-TRH fragment of the prepro-TRH molecule, the connecting peptide PS4 (prepro-TRH 160–169), was able to potentiate the TRH-induced TSH release in a dose-dependent manner, we attempted to determine whether this potentiation might be due to a Ca²⁺-dependent phenomenon and whether a specific class of voltage-dependent Ca²⁺ channels, the L type Ca²⁺ channels, might be involved in the effect of PS4. This was studied by perifusing normal pituitary fragments with medium containing either the Ca²⁺ ionophore, ionomycin, and Co²⁺ ions, or organic compounds well known to block L-type Ca²⁺ channels, and by measuring the TSH response to a pulse of TRH (10 nM) in the presence or absence of PS4 (100 nM). We show that PS4 potentiation of the TRH-induced TSH release (1) was blocked by Co²⁺ (3 mM), a concentration which did not modify significantly the TSH response, while ionomycin potentiated that response, (2) was completely reversed by the dihydropyridine (DHP) nifedipine (10 µM) as well as by the benzothiazepine diltiazem (1 µM) and strongly reduced by the phenylalkylamine verapamil (50 µM) (at the concentrations tested only diltiazem slightly reduced the TSH response to TRH), (3) was abolished by ω-conotoxin GVIA (100 nM), and (4) was completely reversed by perifusion of pertussis toxin (100 ng/ml). Altogether these observations strongly suggest that PS4 potentiation of the TSH response to TRH is a Ca²⁺ -dependent phenomenon, mediated by the activation of DHP- and ω-conotoxin-sensitive Ca²⁺ channels of the L type. A pertussis toxin-sensitive G protein seems to be involved in this process.

show abstract

Evidence that Stimulation of Thyrotropin and Prolactin Secretion by Thyrotropin-Releasing Hormone Occur via Different Calcium-Mediated Mechanisms: Studies with Verapamil*

Cited by 78 publications

References 24 publications

Prostaglandin E₂-Induced Luteinizing Hormone- Releasing Hormone Release Involves Mobilization of Intracellular Ca⁺²*

Prostaglandin E₂-Induced Luteinizing Hormone- Releasing Hormone Release Involves Mobilization of Intracellular Ca⁺²*

The effect of nicardipine on pituitary hormone release in normal volunteers.

A Prepro-TRH Connecting Peptide (Prepro-TRH 160–169) Potentiates TRH-Induced TSH Release from Rat Perifused Pituitaries by Stimulating Dihydropyridine- and Omega-Conotoxin-Sensitive Ca<sup>2+</sup> Channels

Contact Info

Product

Resources

About

Evidence that Stimulation of Thyrotropin and Prolactin Secretion by Thyrotropin-Releasing Hormone Occur via Different Calcium-Mediated Mechanisms: Studies with Verapamil*

Cited by 78 publications

References 24 publications

Prostaglandin E2-Induced Luteinizing Hormone- Releasing Hormone Release Involves Mobilization of Intracellular Ca+2*

Prostaglandin E2-Induced Luteinizing Hormone- Releasing Hormone Release Involves Mobilization of Intracellular Ca+2*

The effect of nicardipine on pituitary hormone release in normal volunteers.

A Prepro-TRH Connecting Peptide (Prepro-TRH 160–169) Potentiates TRH-Induced TSH Release from Rat Perifused Pituitaries by Stimulating Dihydropyridine- and Omega-Conotoxin-Sensitive Ca<sup>2+</sup> Channels

Contact Info

Product

Resources

About

Prostaglandin E₂-Induced Luteinizing Hormone- Releasing Hormone Release Involves Mobilization of Intracellular Ca⁺²*

Prostaglandin E₂-Induced Luteinizing Hormone- Releasing Hormone Release Involves Mobilization of Intracellular Ca⁺²*