Effect of Cabergoline, a Dopamine Agonist, on Estrogen-Induced Rat Pituitary Tumors: In Vitro Culture Studies.

Eguchi, Kuniki; Kawamoto, Keiichi; Uozumi, Tohru; Ito, Akihiro; Arita, Kazunori; Kurisu, Kaoru

doi:10.1507/endocrj.42.413

Cited by 23 publications

(13 citation statements)

References 39 publications

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“…This drug suppresses PRL release in in vitro and in vivo rodent models [11], [12], and decreases cell viability in non-functioning human pituitary adenomas [36]. We previously reported that CAB induces apoptosis of lactotropes only when cells are cultured in the presence of E2 [2].…”

Section: Discussionmentioning

confidence: 99%

“…Cabergoline (CAB), a D2R agonist, is the most effective compound for pharmacological treatment of prolactinomas [10], strongly reducing PRL secretion and lactotrope proliferation [11], [12]. Although DA agonists have been proven to be successful in normalizing serum PRL levels, a subset of patients with prolactinomas does not respond to CAB, suggesting that D2R expression is altered.…”

Section: Introductionmentioning

confidence: 99%

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Dopamine-Induced Apoptosis of Lactotropes Is Mediated by the Short Isoform of D2 Receptor

et al. 2011

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Dopamine, through D2 receptor (D2R), is the major regulator of lactotrope function in the anterior pituitary gland. Both D2R isoforms, long (D2L) and short (D2S), are expressed in lactotropes. Although both isoforms can transduce dopamine signal, they differ in the mechanism that leads to cell response. The administration of D2R agonists, such as cabergoline, is the main pharmacological treatment for prolactinomas, but resistance to these drugs exists, which has been associated with alterations in D2R expression. We previously reported that dopamine and cabergoline induce apoptosis of lactotropes in primary culture in an estrogen-dependent manner. In this study we used an in vivo model to confirm the permissive action of estradiol in the apoptosis of anterior pituitary cells induced by D2R agonists. Administration of cabergoline to female rats induced apoptosis, measured by Annexin-V staining, in anterior pituitary gland from estradiol-treated rats but not from ovariectomized rats. To evaluate the participation of D2R isoforms in the apoptosis induced by dopamine we used lactotrope-derived PR1 cells stably transfected with expression vectors encoding D2L or D2S receptors. In the presence of estradiol, dopamine induced apoptosis, determined by ELISA and TUNEL assay, only in PR1-D2S cells. To study the role of p38 MAPK in apoptosis induced by D2R activation, anterior pituitary cells from primary culture or PR1-D2S were incubated with an inhibitor of the p38 MAPK pathway (SB203850). SB203580 blocked the apoptotic effect of D2R activation in lactotropes from primary cultures and PR1-D2S cells. Dopamine also induced p38 MAPK phosphorylation, determined by western blot, in PR1-D2S cells and estradiol enhanced this effect. These data suggest that, in the presence of estradiol, D2R agonists induce apoptosis of lactotropes by their interaction with D2S receptors and that p38 MAPK is involved in this process.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Dopamine-Induced Apoptosis of Lactotropes Is Mediated by the Short Isoform of D2 Receptor

et al. 2011

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“…Cabergoline 7.1 Therapeutic profile CAB strongly suppresses PRL secretion both in vivo and in vitro. A significant inhibition of PRL secretion was observed within 12 h after treatment with CAB and BRC in cultured pituitary cells from oestradiol-induced rat pituitary tumours [63,64]. The effect of CAB and BRC was antagonised by sulpiride or haloperidol and PRL secretion and inhibition of de novo synthesis was more pronounced with CAB than BRC treatment [64].…”

Section: Othersmentioning

confidence: 96%

“…A significant inhibition of PRL secretion was observed within 12 h after treatment with CAB and BRC in cultured pituitary cells from oestradiol-induced rat pituitary tumours [63,64]. The effect of CAB and BRC was antagonised by sulpiride or haloperidol and PRL secretion and inhibition of de novo synthesis was more pronounced with CAB than BRC treatment [64]. In various animal models, CAB markedly reduced plasma PRL levels in vivo after single or multiple doses and the PRL-lowering effects appeared 2 -8 h after administration lasting for ≥ 72 h [65,66].…”

Section: Othersmentioning

confidence: 98%

Dopamine receptor agonists for treating prolactinomas

Colao¹,

A²,

Pivonello³

et al. 2002

Expert Opinion on Investigational Drugs

121

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Prolactinomas are the most common hormone-secreting pituitary tumours and cause infertility and gonadal and sexual dysfunction in both sexes. The approach to prolactinomas has changed in the last 25 years thanks to the availability of dopaminergic drugs characterised by a potent prolactin-inhibitory effect, a tumour shrinking effect associated with a satisfactory tolerability. In more recent years, cabergoline 1-[(6-allelylergolin-8beta-yl)carbonyl]-1-[3-(dimethylamino) propyl]-3-ethyl-urea an ergoline derivative with potent, selective and long-lasting inhibitory activity on prolactin release, has been used to suppress prolactin secretion in women with hyperprolactinaemia. Cabergoline was shown to be significantly more effective than bromocriptine in inducing a complete biochemical response and clinical efficacy and was better tolerated than bromocriptine in the majority of patients. Notable tumour shrinkage until tumour disappearance was observed during cabergoline treatment in most patients with macroprolactinoma and it was also proven effective in patients resistant to or with a poor response to bromocriptine. In view of the limited data on cabergoline-associated pregnancies and the long half-life of the drug, it is currently recommended that women hoping to become pregnant, once ovulatory cycles have been established, should discontinue cabergoline therapy 1 month before they intend to conceive. However, no data concerning negative effects on pregnancy or offspring have been reported. The great efficacy of this compound together with its excellent tolerability makes this drug the current treatment of choice for the majority of patients with hyperprolactinaemic disorders.

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“…Cabergoline, a selective D2 agonist, strongly suppresses PRL secretion and synthesis (9). A remarkable tumor-shrinking effect has been recognized in patients with not only microprolactinomas but also macroprolactinomas (10).…”

Section: Discussionmentioning

confidence: 99%

Cabergoline Effectively Induced Remission of Prolactinoma in a 9-year-old Japanese Boy

Sano

Takigami

Ogino

et al. 2009

Clin Pediatr Endocrinol

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Prolactinomas are rarely diagnosed in children under the age of 10. A 9-yr-old Japanese boy complained of severe headache and progressive visual disturbance. His growth had been retarded for approximately 3 yr, and his serum PRL level was 811.6 ng/ml. Brain magnetic resonance imaging (MRI) revealed an enlarged pituitary (2.8 × 2.6 × 2.1 cm) with heterogeneous enhancement. He was diagnosed as having a macroprolactinoma accompanied by pituitary apoplexy and growth hormone deficiency. A surgical approach was initially undertaken due to the progressive visual deficits, but a residual tumor was observed, and the level of serum PRL was still high after the surgery. Cabergoline was then started, and the dose was gradually increased to 1.5 mg/wk. The serum PRL level decreased from 138.8 ng/ml to 32.5 ng/ml and 17.7 ng/ml after 5 wk and 19 wk, respectively. At 33 wk of cabergoline treatment, brain MRI demonstrated no evidence of the residual tumor. Thereafter, the serum level of PRL decreased to less than 10 ng/ml, and remission was consistently confirmed on repeated MRI. No adverse events have been observed. The present case suggests that cabergoline can be an effective treatment for prolactinomas in prepubertal children as well as in adults.

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Effect of Cabergoline, a Dopamine Agonist, on Estrogen-Induced Rat Pituitary Tumors: In Vitro Culture Studies.

Cited by 23 publications

References 39 publications

Dopamine-Induced Apoptosis of Lactotropes Is Mediated by the Short Isoform of D2 Receptor

Dopamine-Induced Apoptosis of Lactotropes Is Mediated by the Short Isoform of D2 Receptor

Dopamine receptor agonists for treating prolactinomas

Cabergoline Effectively Induced Remission of Prolactinoma in a 9-year-old Japanese Boy

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