Dopamine D2 receptor expression and regulation of gonadotropin α-subunit gene in clonal gonadotroph LβT2 cells

Mutiara, Sandra; Kanasaki, Haruhiko; Harada, Takashi; Miyazaki, Kohji

doi:10.1016/j.mce.2006.07.005

Cited by 17 publications

(11 citation statements)

References 40 publications

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“…The sensitizing action of estrogens may involve the modulation of D2 receptor expression [29, 30] and/or changes in the signal transduction pathways triggered by D2 receptor activation. The permissive effect of E2 on DA-induced apoptosis could be exerted not only on lactotrophs but also on other anterior pituitary cell types where DA receptors are expressed, such as corticotrophs [31], somatotrophs [32], and gonadotrophs [33]. …”

Section: Discussionmentioning

confidence: 99%

Apoptosis of Lactotrophs Induced by D2 Receptor Activation Is Estrogen Dependent

Radl

Zárate²,

Jaita³

et al. 2008

Neuroendocrinology

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Background/Aims: Dopamine (DA) inhibits prolactin release and reduces lactotroph proliferation by activating D2 receptors. DA and its metabolite, 6-hydroxydopamine (6-OHDA), induce apoptosis in different cell types. DA receptors and DA transporter (DAT) were implicated in this action. Considering that estradiol sensitizes anterior pituitary cells to proapoptotic stimuli, we investigated the effect of estradiol on the apoptotic action of DA and 6-OHDA in anterior pituitary cells, and the involvement of the D2 receptor and DAT in the proapoptotic effect of DA. Methods: Viability of cultured anterior pituitary cells from ovariectomized rats was determined by MTS assay. Apoptosis was evaluated by Annexin-V/flow cytometry and TUNEL. Lactotrophs were identified by immunocytochemistry. Results: DA induced apoptosis of lactotrophs in an estrogen-dependent manner. In contrast, estradiol was not required to trigger the apoptotic action of 6-OHDA. Cabergoline, a D2 receptor agonist, induced lactotroph apoptosis, while sulpiride, a D2 receptor antagonist, blocked DA-induced cell death. The blockade of DAT by GBR12909 did not affect the apoptotic action of DA, but inhibited 6-OHDA-induced apoptosis. Conclusion: These data show that DA, through D2 receptor activation, induces apoptosis of estrogen-sensitized anterior pituitary cells, and suggest that DA contributes to the control of lactotroph number not only by inhibiting proliferation but also by inducing apoptosis.

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Section: Discussionmentioning

confidence: 99%

Apoptosis of Lactotrophs Induced by D2 Receptor Activation Is Estrogen Dependent

Radl

Zárate²,

Jaita³

et al. 2008

Neuroendocrinology

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“…Notably, studies by our group have shown that in ovine and equine primary pituitary cell cultures, PRL suppresses the LH response to GnRH only when applied concomitantly with bromocriptine (Br), a dopamine (DA) agonist [8,9]. Moreover, in the ovine pituitary, the PRL receptor (PRLR) is selectively expressed in the gonadotroph [10], and in the LbT2 gonadotroph cell line, the expression of both the PRLR and DA-2 receptor (DRD2) has been documented [11,12]. Therefore, PRL and DA can act directly at the level of the gonadotroph to evoke their effects.…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, PRL and DA can act directly at the level of the gonadotroph to evoke their effects. However, whereas the cellular and molecular effects of DA in the gonadotroph are reasonably well defined [11,13], those of PRL are not.…”

Section: Introductionmentioning

confidence: 99%

Characterization of the Effects of Prolactin in Gonadotroph Target Cells1

Hodson

Townsend

Tortonese

2010

Biology of Reproduction

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Hyperprolactinemia is a major cause of infertility, brought about by inhibition of gonadotropin-releasing hormone (GnRH) secretion from the hypothalamus and impairment of luteinizing hormone (LH) output from the pituitary gland. However, whereas the actions of prolactin (PRL) within the brain have been investigated extensively, its specific effects at the level of pituitary gonadotroph target cells remain unclear. Here, we provide evidence that the actions of PRL within the gonadotroph are more complex than originally envisaged. Using a gonadotroph cell monoculture, the first series of experiments showed that PRL is, paradoxically, a potent stimulator of LH release, with a three- to fourfold increase in LH values at hyperprolactinemic concentrations of PRL. Conversely, PRL dose-dependently modulated the LH secretory response to GnRH in a biphasic manner, with classical suppression of LH output only detected under a narrow dose range. In contrast, at all doses tested, PRL blocked the LHB mRNA response to the secretagogue. Subsequent studies revealed that the stimulatory effects of PRL on LH release are not mediated by the conventional cytokine receptor pathways but, rather, by a novel JAK2-PIK3-PKC-dependent signaling cascade. Moreover, the experiments showed that these actions of PRL within gonadotroph cells are controlled by dopamine, the main hypothalamic inhibitory regulator of PRL release in vivo. Our findings have unraveled specific actions of PRL within the gonadotroph and the cell-signaling interactions that ultimately underlie hyperprolactinemia-induced infertility.

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“…Quantification of LHβ and FSHβ mRNA expression was obtained through realtime quantitative PCR (ABI Prism 7700 Sequence Detector; Perkin Elmer Applied Biosystems, Foster City, CA) with Brilliant SYBR Green QPCR Master Mix (Stratagene, La Jolla, CA). The PCR primers were designed based on the published sequences of α, LHβ and FSHβ [16,17], while the internal reference GAPDH primer was purchased from Sigma Chemical Co. (St. Louis, MO). Real-time PCR amplification and product detection were performed using an ABI PRISM 7700 Sequence Detection System (Perkin Elmer Applied Biosystems) as recommended by the to selectively stimulate gonadotropin synthesis and release, affecting only FSH.…”

Section: Rna Preparation Reverse Transcription and Realtime Quantitamentioning

confidence: 99%

Trichostatin A specifically stimulates gonadotropin FSHβ gene expression in gonadotroph LβT2 cells

et al. 2014

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Mediation of reproductive functions in mammals is mainly controlled by pituitary gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH). These gonadotropins are involved in follicular growth, oocyte maturation and sex steroid synthesis within the ovaries [1]. LH and FSH contain a common α and specific , and are principally controlled by hypothalamic gonadotropin-releasing hormone (GnRH). GnRH is released into the hypophyseal portal circulation in a pulsatile manner, and the pattern of this pulse, which varies physiologically during the reproductive cycle, determines the specificity of LH and FSH synthesis and secretion abstract. Trichostatin A (TSA) is a selective inhibitor of mammalian histone deacetylase. In the present study, TSA was found to selectively increase gene expression of the pituitary gonadotropin β-subunit of follicle-stimulating hormone (FSH). Stimulation of mouse pituitary gonadotroph cell lines, LβT2, with TSA for 24 h resulted in no change in mRNA expression of the α-and LHβ-subunit. On the other hand, FSHβ-subunit mRNA expression was significantly increased in a dose-dependent fashion. Similarly, specific induction of the FSHβ-subunit gene with TSA stimulation was observed in primary cultures of rat pituitary cells. Histone acetylation in whole cell lysates of LβT2 cells was significantly increased after TSA treatment, but not gonadotropin-releasing hormone (GnRH) treatment. The effect of TSA on FSHβ mRNA expression was prominent compared to that of GnRH; however, TSA-stimulated FSHβ mRNA expression was significantly reduced with combined TSA and GnRH treatment. TSA caused a slight increase in extracellular signal-regulated kinase (ERK) phosphorylation, while GnRH-increased ERK phosphorylation was potentiated in the presence of TSA. In addition, TSA, but not GnRH, significantly stimulated gene expression of retinaldehyde dehydrogenase 1 (RALDH1), a retinoic acid (RA) synthesizing enzyme involved in cell differentiation. These findings demonstrate that TSA specifically increases FSHβ subunit gene expression with a concomitant increase in whole cell histone acetylation. Moreover, although GnRH is a stimulator of FSHβ gene expression, it interfered with the stimulatory effect of TSA on FSHβ mRNA expression, without modification of TSA-increased whole cell histone acetylation. This suggests that the mechanisms of TSA and GnRH-induced gonadotropin subunit gene expression are entirely distinct.Key words: Trichostatin A, Gonadotropin, FSH, Gene expression frequency differentially regulate the release of LH and FSH from the hypothalamus [4]. Using an ovariectomized monkey with an artificially destroyed hypothalamus, they demonstrated that administration of a rapid-frequency GnRH pulse increased secretion of LH, whereas a slower frequency decreased secretion but increased FSH secretion. GnRH pulse frequency-dependent specific regulation of LHβ-and FSHβ-subunit gene expression was also observed in the mice gonadotroph cell line LβT2 [5]. However, the detailed mechanisms behind ...

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Dopamine D2 receptor expression and regulation of gonadotropin α-subunit gene in clonal gonadotroph LβT2 cells

Cited by 17 publications

References 40 publications

Apoptosis of Lactotrophs Induced by D2 Receptor Activation Is Estrogen Dependent

Apoptosis of Lactotrophs Induced by D2 Receptor Activation Is Estrogen Dependent

Characterization of the Effects of Prolactin in Gonadotroph Target Cells1

Trichostatin A specifically stimulates gonadotropin FSHβ gene expression in gonadotroph LβT2 cells

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