Effects of bromocriptine on cell cycle distribution and cell morphology in cultured rat pituitary adenoma cells

Johansen, Per Wiik; Clausen, O. P. F.; Haug, Egil; Fossum, Sigbjørn; Gautvik, Kaare M.

doi:10.1530/acta.0.1100319

Cited by 17 publications

(11 citation statements)

References 7 publications

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“…Ultrastructural studies following bromocriptine administration indicated nuclear pyknosis, aggregated chromatin, and reduction of volume densities of rough endoplasmic reticulum and Golgi apparatus [3,4]. A significant reduction in the volume of the cytoplasm was observed; atrophy or swelling of mitochondria was also evident [5]. These findings suggest that bromocriptine has cytotoxic and antimitotic effects.…”

Section: Introductionmentioning

confidence: 81%

“…Johansen et al [26] showed that prolonged treatment of GH3 cells with bromocriptine significantly reduced the production of prolactin and GH and inhibited cell growth. Treatment with bromocriptine also caused an appearance of vacuoles in the cytosol and condensation of the nucleus and the mitochondria [5]. Furthermore, long-term incubation with bromocriptine caused a cytotoxic effect in GH3 cells [27] and apoptosis in GHsecreting cell line GH1 cells [28], ACTH-secreting cell line AtT-20 cells [29], and normal rat anterior pituitary cells [30].…”

Section: Discussionmentioning

confidence: 98%

“…Indeed, stimulation of the dopamine D 2 receptor is known to inhibit prolactin secretion through inhibition of cAMP production and/or cytosolic Ca 2ϩ elevation [1,2]. Furthermore, the cytotoxic and antiproliferative effects of bromocriptine have been reported [3][4][5]. Ultrastructural studies following bromocriptine administration indicated nuclear pyknosis, aggregated chromatin, and reduction of volume densities of rough endoplasmic reticulum and Golgi apparatus [3,4].…”

Section: Introductionmentioning

confidence: 99%

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Involvement of p38 Mitogen-Activated Protein Kinase Activation in Bromocriptine-Induced Apoptosis in Rat Pituitary GH3 Cells1

Kanasaki¹,

Fukunaga²,

Takahashi³

et al. 2000

Biology of Reproduction

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Bromocriptine, a dopamine D 2 receptor agonist, is a therapeutic agent for patients with prolactinoma and hyperprolactinemia. In this study we demonstrated that bromocriptine induced activation of p38 mitogen-activated protein (MAP) kinase, with concomitant induction of apoptosis in rat pituitary adenoma cell line GH3 cells. Treatment of GH3 cells for 48 h with bromocriptine increased the p38 MAP kinase activity up to 3-to 5-fold and simultaneously increased the number of apoptotic cells. Inclusion in the medium of SB212090 or SB203580, specific p38 MAP kinase inhibitors, completely abolished the bromocriptineinduced activation of p38 MAP kinase and significantly reduced the number of apoptotic cells. The bromocriptine-induced p38 MAP kinase activation was not prevented by S(Ϫ)-eticropride hydrochloride, a specific D 2 receptor antagonist. Treatment with either epidermal growth factor (EGF) or thyrotropin-releasing hormone (TRH), which stimulates p44/42 MAP kinase, rescued cells from the bromocriptine-induced apoptosis, with concomitant inhibition of the bromocriptine-induced p38 MAP kinase activation. These results suggest that bromocriptine induces apoptosis in association with p38 MAP kinase activation, and that the p44/42 MAP kinase signaling through EGF and TRH receptors has an opposing effect on p38 MAP kinase activation as well as on apoptosis induced with bromocriptine in GH3 cells.

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Section: Introductionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

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Involvement of p38 Mitogen-Activated Protein Kinase Activation in Bromocriptine-Induced Apoptosis in Rat Pituitary GH3 Cells1

Kanasaki¹,

Fukunaga²,

Takahashi³

et al. 2000

Biology of Reproduction

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“…We have previously shown that many signal transduction effects caused by TRH in pituitary adenoma cells (GH cells) in culture, are inhibited or abolished by bromocriptine. These effects could be explained by inhibition of G-protein actions (G i2 , G o , G s and G q/11 ) (56,57). In addition to these TRH-inhibitory actions, bromocriptine has also been shown to stimulate the pituitary TRH degrading enzyme (TRHDE), a TRH-specific ectoenzyme responsible for the inactivation of TRH (58).…”

Section: Discussionmentioning

confidence: 99%

Thyrotrophin-releasing hormone receptor 1 and prothyrotrophin-releasing hormone mRNA expression in the central nervous system are regulated by suckling in lactating rats

Fjeldheim¹,

Høvring²,

Løseth³

et al. 2005

eur j endocrinol

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Background: The accepted function of the hypothalamic peptide, thyrotrophin-releasing hormone (TRH), is to initiate release of thyrotrophin (TSH) from the pituitary. A physiological role for TRH in lactating rats has not yet been established. Methods: Tissues were prepared from random-cycling and lactating rats and analysed using Northern blot, real time RT-PCR and quantitative in situ hybridisation.Results: This study demonstrates that TRH receptor 1 (TRHR1) mRNA expression is up-regulated in the pituitary and in discrete nuclei of the hypothalamus in lactating rats, while proTRH mRNA expression levels are increased only in the hypothalamus. The results were corroborated by quantitative in situ analysis of proTRH and TRHR1. Bromocriptine, which reduced prolactin (PRL) concentrations in plasma of lactating and nursing rats, also counteracted the suckling-induced increase in TRHR1 mRNA expression in the hypothalamus, but had an opposite effect in the pituitary. These changes were confined to the hypothalamus and the amygdala in the brain.Conclusions: The present study shows that the mechanisms of suckling-induced lactation involve region-specific regulation of TRHR1 and proTRH mRNAs in the central nervous system notably at the hypothalamic level. The results demonstrate that continued suckling is critical to maintain plasma prolactin (PRL) levels as well as proTRH and TRHR1 mRNA expression in the hypothalamus. Increased plasma PRL levels may have a positive modulatory role on the proTRH/TRHR1 system during suckling.

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“…Previous studies have shown that bromocriptine at high concentrations also induces general phenotypic changes in GH 3 cells, thereby suggesting a possible general, non-receptor mediated action of the drug [25,26]. Low affinity D 2 Rs have so far not been considered to be of major importance in the regulation of vital biological responses.…”

Section: Introductionmentioning

confidence: 99%

Distinct Guanine Nucleotide Binding Protein Alpha-Subunit Receptor Coupling in GH Cell Lines: <i>Effects of Bromocriptine and Hormones on Effector Enzyme Modulation</i>

Johansen

Paulssen²,

Bjøro³

et al. 2001

Cell Physiol Biochem

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The purpose of the present study was to elucidate how the dopamine agonist bromocriptine affected receptor-effector systems in GH cells by measuring adenylate cyclase (AC) and phospholipase C (PL-C) modulation in cell membrane preparations. To perturb the interaction between the receptor and G-protein, polyclonal antibodies reacting with the predicted C-terminal amino acid sequence of G-protein α-subunits were used. The effect of bromocriptine on secretagogue elicited prolactin (PRL) secretion from whole cells was also monitored. Bromocriptine inhibited the basal secretion of PRL in a dose dependent manner, and completely abolished both the thyroliberin (TRH) and the vasoactive intestinal peptide (VIP) stimulated PRL secretion in GH₃ cells. Maximal inhibitory effect on PRL egress elicited by both hormones was obtained at 10-50 µM of bromocriptine. Messenger RNAs for both the short and long form of the D₂ receptor (D₂R) were demonstrated in all three GH cell lines using the RT-PCR technique, advocating that D₂Rs are coupled to distinct G-proteins and, thus, probably being responsible for the observed effects of bromocriptine in these cell lines. Basal AC activity, as measured in membrane preparations of GH₃ cells, remained unaffected by bromocriptine treatment (10 µM), while TRH and VIP stimulated AC activities (175% and 350% of control values, respectively) were partially inhibited (by some 50%). This inhibitory effect of bromocriptine was completely and specifically abolished in the presence of an antiserum against G_i2α. Basal PL-C activity was also unaffected by bromocriptine, while TRH stimulated PL-C activity (350% of control value) was inhibited by bromocriptine (10 µM) by approximately 50%. Immunoblocking of G_q/11α, however, reduced the stimulatory effect of TRH on PL-C activation by some 65%, while an antiserum against G_oα partly counteracted the inhibitory effect of bromocriptine (10 µM) on TRH stimulated PL-C activity. Thus, TRH dependent AC stimulation was counteracted by bromocriptine via G_i2. TRH activation of PL-C occurs via G_q/11, while inhibition by bromocriptine appears to involve G_o. These mechanisms probably account for the major part of the actions of bromocriptine, however, other not yet recognised intermediates may be involved.

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Effects of bromocriptine on cell cycle distribution and cell morphology in cultured rat pituitary adenoma cells

Abstract: The effects of bromocriptine, a dopamine

Cited by 17 publications

References 7 publications

Involvement of p38 Mitogen-Activated Protein Kinase Activation in Bromocriptine-Induced Apoptosis in Rat Pituitary GH3 Cells1

Involvement of p38 Mitogen-Activated Protein Kinase Activation in Bromocriptine-Induced Apoptosis in Rat Pituitary GH3 Cells1

Thyrotrophin-releasing hormone receptor 1 and prothyrotrophin-releasing hormone mRNA expression in the central nervous system are regulated by suckling in lactating rats

Distinct Guanine Nucleotide Binding Protein Alpha-Subunit Receptor Coupling in GH Cell Lines: <i>Effects of Bromocriptine and Hormones on Effector Enzyme Modulation</i>

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