Correlation of alternative splicing of the D2 dopamine receptor mRNA and estrogen receptor mRNA in the prolactinomas and gonadotrope tumors

Wu, Zhe Bao; Li, Chu Zhong; Zong, Xu; Su, Zhi Peng; Zeng, Yan; Zhang, Ya Zhuo

doi:10.1007/s11060-009-9816-5

Cited by 8 publications

(7 citation statements)

References 16 publications

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“…Our data supported the findings of Wu et al [41] reporting that 17β-estradiol acted to modulate the ratio of the two isoforms of the dopamine D2 receptor (D2L/D2S), by transcription of their respective genes, through nuclear estrogen receptors induction, thereby highlighting functional difference between the two isoforms. The two isoforms coexisted in most brain tissue analyzed and the ratio of D2L versus D2S mRNA expressions varied from region to region [88] [89].…”

Section: A Bâ Et Al Journal Of Behavioral and Brain Sciencesupporting

confidence: 92%

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Effects of Ovariectomy and 17β-Estradiol Replacement on Dopamine D2 Receptors in Female Rats: Consequences on Sucrose, Alcohol, Water Intakes and Body Weight

Bâ¹,

Silué²,

Bamba³

et al. 2018

JBBS

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Background: Mechanisms underlying overeating-induced obesity in postmenopausal woman include functional lack of 17β-estradiol dysregulating dopamine D2 receptors, thereby inducing food addiction, glucose craving or alcohol dependence through reward circuitry. This study aimed at further understanding 17β-estradiol and dopamine D2 receptors interferences in the etiology of woman obesity. Method: Seventy-two Wistar female rats weighing 200 -205 g, individually-housed, were divided into non-ovariectomized control (C = 6 groups) and ovariectomized rats (OVX = 6 groups) which were concurrently subjected to the following treatments: Non-drug-treated (DMSO vehicle), 17β-estradiol (E2, 5 µg/kg, s.c.), sulpiride (SUL, 20 mg/kg, i.p.), bromocriptine (BR, 0.1 mg/kg, i.p.), E2 + SUL or E2 + BR, designating the 6 constitutive groups of either control or ovariectomy. Within each experimental group, consumption of different solutions (10% alcohol, 10% sucrose and water) as well as food intake and body weight were daily measured, for 10 consecutive days. Results: This study indicated that D2S was a specific inducer of alcohol and food intakes, but reduced sugar consumption. In addition, 17β-estradiol regulated the body weight set point, modulating D2S functions towards increased food intake at lower weights and decreased food intake at higher weights. D2S met the slow genomic actions induced by 17β-estradiol. Conversely, D2L inhibited alcohol and food intakes, but induced specifically sugar consumption, thereby regulating blood glucose levels and promoting energy expenditure in reducing body weight. Indeed, 17β-estradiol exerted a tonic inhibition on D2L which was released by OVX, exacerbating sugar intake and increasing body weight. D2L mediated the rapid metabolic effects of that activation of the mostly expressed presynaptically D2S-class autoreceptors decreased dopamine release stimulating food intake, whereas activation of the predominantly postsynaptic isoform D2L receptors increased dopamine activity inhibiting food intake. Our studies indicated that 17β-estradiol acted on the two types of D2 receptors showing opposite functions to equilibrate energy intake vs. expenditure for weight set point regulation. Our data also supported biochemical findings reporting that 17β-estradiol induced D2 genes transcriptional regulation, thereby involving both types of D2 receptors in the etiology of obesity. The combined dysregulated effects of D2L and D2S receptors, as 17β-estradiol was lacking, would be causal factors underlying the etiology of obesity.

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Section: A Bâ Et Al Journal Of Behavioral and Brain Sciencesupporting

confidence: 92%

“…For instance, the 17β-estradiol regulated through its slow genomic actions, the transcription and synthesis of both D2L and D2S isoforms [40] [41].…”

Section: Introductionmentioning

confidence: 99%

Effects of Ovariectomy and 17β-Estradiol Replacement on Dopamine D2 Receptors in Female Rats: Consequences on Sucrose, Alcohol, Water Intakes and Body Weight

Bâ¹,

Silué²,

Bamba³

et al. 2018

JBBS

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show abstract

“…E 2 is known to affect D2 receptor splicing and increases the ratio of D2L and D2S receptor numbers or mRNA levels in lactotropes (Guivarc'h et al 1998, Oomizu et al 2003. This differential splicing of D2 receptor isoforms might be a critical mechanism of E 2 action on lactotropes, as a negative correlation between D2S and ERa mRNA expression and a positive correlation between D2L and ERa mRNA expression were found in human prolactinomas (Wu et al 2009). The data obtained from this study also indicated that E 2 was able to markedly increase PRL production and cell proliferation in cells expressing D2S receptor but produced a very moderate effect in cells producing D2L receptors.…”

Section: Discussionmentioning

confidence: 99%

Estrogen inhibits D2S receptor-regulated Gi3 and Gs protein interactions to stimulate prolactin production and cell proliferation in lactotropic cells

Sengupta

Sarkar

2012

Journal of Endocrinology

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The neurotransmitter dopamine (DA) is known to inhibit prolactin (PRL) secretion and the proliferation of lactotropes in the pituitary gland. Dopamine-2 (D2) receptor short (D2S) isoform is expressed in a reduced level while the D2 receptor long (D2L) isoform is expressed in an elevated level during estradiol (E 2 )-induced PRL production and cell proliferation in lactotropes. To evaluate the role of these D2 receptor isoforms in E 2 -regulated lactotropic cell function, we compared E 2 effects on the level of PRL, cell proliferation, and G proteins in enriched lactotropes and lactotrope-derived PR1 cells containing only D2S isoform (D2S cells), D2L isoform (D2L cells), or no D2 receptor (V cells). Additionally, we determined the effects of G protein blockade on the E 2 -induced PRL production and cell proliferation in these cells.We here show that E 2 actions on G proteins, PRL production, and cell proliferation were maximally achieved in D2S cells, oppositely or marginally achieved in D2L cells, and absent in V cells. We also show that the DA and pertussis toxin modulations of E 2 actions on PRL, G proteins, and cell proliferation were maximally achieved in D2S cells compared with in D2L or V cells. Furthermore, we provide evidence for the existence of an inhibitory action of Gi3 on Gs that is under the control of the D2S receptor and is inhibited by E 2 . These results suggest that the suppression of D2S-regulated Gi3 inhibition of Gs protein may be one of the mechanisms controlling E 2 -activated PRL synthesis and cell proliferation in lactotropes.

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“…Estradiol induces tyrosine hydroxylase gene transcription with estradiol receptor-alpha (ER-alpha), [9], requiring cAMP/calcium responses and protein kinase pathways [15], thereby increases activation of dopamine neurons [16]. For instance, the 17β-estradiol regulated through its slow Journal of Biosciences and Medicines genomic actions, the transcription and synthesis of both D2L and D2S dopamine receptors isoforms [18] [19].…”

Section: Introductionmentioning

confidence: 99%

Effects of 17β-Estradiol on Dopamine D2 Receptors in Thiamine-Deficient Female Rats: Consequences on Sucrose, Alcohol, Water Intakes and Body Weight

Silué¹,

acirc²

2019

JBM

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Our previous studies showed that 17β-estradiol (E2) modulated dopamine D2 receptor in regulating body weight set-point. The aim of this study was to understand whether thiamine deficiency influenced the E2 modulation on dopamine D2 receptors, using bromocriptine mesylate (BR) and sulpiride (SUL) as selective central dopamine-D2 receptors agonist and antagonist respectively. We studied the E2-dopamine D2 receptors interferences in a 10-day thiamine-deficient female rats for which consumptions of water, sugar, alcohol and food were daily-recorded and their consequences on body weights assessed. Our results showed that the volume of water daily ingested doubled in thiamine-deficient female rats (OXT), while sugar and alcohol consumptions collapsed with decreased weight and food consumption. On the one hand, thiamine potentiated D2/BR activity (bromocriptine-activated D2 receptors) to induce sugar intake and inhibited the same D2/BR receptors to induce water intake. On the other hand, thiamine promoted D2/SUL receptors (sulpiride-inhibited D2 receptors) for enhanced alcohol intake, increased food consumption and weight gain. Taking together, thiamine modulated the actions of 17β-estradiol on both D2/BR and D2/SUL receptors activities.

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Correlation of alternative splicing of the D2 dopamine receptor mRNA and estrogen receptor mRNA in the prolactinomas and gonadotrope tumors

Abstract: This study for the first time shows a good correlation between expression of ER and D2R isoforms in prolactinomas and gonadotrope tumors. Reducing the amount of the ERalpha in neoplasm cells can alter the ratio of D2L/D2S, which may increase the drug sensitivity of pituitary adenomas.

Cited by 8 publications

References 16 publications

Effects of Ovariectomy and 17<i>β</i>-Estradiol Replacement on Dopamine D2 Receptors in Female Rats: Consequences on Sucrose, Alcohol, Water Intakes and Body Weight

Effects of Ovariectomy and 17<i>β</i>-Estradiol Replacement on Dopamine D2 Receptors in Female Rats: Consequences on Sucrose, Alcohol, Water Intakes and Body Weight

Estrogen inhibits D2S receptor-regulated Gi3 and Gs protein interactions to stimulate prolactin production and cell proliferation in lactotropic cells

Effects of 17<i>β</i>-Estradiol on Dopamine D2 Receptors in Thiamine-Deficient Female Rats: Consequences on Sucrose, Alcohol, Water Intakes and Body Weight

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Correlation of alternative splicing of the D2 dopamine receptor mRNA and estrogen receptor mRNA in the prolactinomas and gonadotrope tumors

Abstract: This study for the first time shows a good correlation between expression of ER and D2R isoforms in prolactinomas and gonadotrope tumors. Reducing the amount of the ERalpha in neoplasm cells can alter the ratio of D2L/D2S, which may increase the drug sensitivity of pituitary adenomas.

Cited by 8 publications

References 16 publications

Effects of Ovariectomy and 17&lt;i&gt;β&lt;/i&gt;-Estradiol Replacement on Dopamine D2 Receptors in Female Rats: Consequences on Sucrose, Alcohol, Water Intakes and Body Weight

Effects of Ovariectomy and 17&lt;i&gt;β&lt;/i&gt;-Estradiol Replacement on Dopamine D2 Receptors in Female Rats: Consequences on Sucrose, Alcohol, Water Intakes and Body Weight

Estrogen inhibits D2S receptor-regulated Gi3 and Gs protein interactions to stimulate prolactin production and cell proliferation in lactotropic cells

Effects of 17&lt;i&gt;β&lt;/i&gt;-Estradiol on Dopamine D2 Receptors in Thiamine-Deficient Female Rats: Consequences on Sucrose, Alcohol, Water Intakes and Body Weight

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Effects of Ovariectomy and 17<i>β</i>-Estradiol Replacement on Dopamine D2 Receptors in Female Rats: Consequences on Sucrose, Alcohol, Water Intakes and Body Weight

Effects of Ovariectomy and 17<i>β</i>-Estradiol Replacement on Dopamine D2 Receptors in Female Rats: Consequences on Sucrose, Alcohol, Water Intakes and Body Weight

Effects of 17<i>β</i>-Estradiol on Dopamine D2 Receptors in Thiamine-Deficient Female Rats: Consequences on Sucrose, Alcohol, Water Intakes and Body Weight