A Composite Element that Binds Basic Helix Loop Helix and Basic Leucine Zipper Transcription Factors Is Important for Gonadotropin-Releasing Hormone Regulation of the Follicle-Stimulating Hormone β Gene

Ciccone, Nick A.; Lacza, Charlemagne; Hou, Melody Y.; Gregory, Susan J.; Kam, Kyung-Yoon; Xu, Shuyun; Kaiser, Ursula B.

doi:10.1210/me.2007-0455

Cited by 41 publications

(45 citation statements)

References 59 publications

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“…The finding that G␣ s contributed to suppression of FSH␤ mRNA was unexpected, as the FSH␤ promoter has been reported to have activating CREB sites that could be stimulated by G␣ s signaling (40). Experiments using separate individual G␣ s siRNAs and stimulatory experiments in the gonadotrope cell line and in primary mouse gonadotrope cells using CTX confirmed that the major effect of G␣ s signaling on FSH␤ expression was inhibitory.…”

Section: Discussionmentioning

confidence: 97%

G Proteins and Autocrine Signaling Differentially Regulate Gonadotropin Subunit Expression in Pituitary Gonadotrope

Choi¹,

Jia²,

Pfeffer³

et al. 2012

Journal of Biological Chemistry

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Background:The mechanism for differential control of gonadotropin gene induction by GnRH is not established. Results: GnRH activates G␣ s and G␣ q/11 , which modulate LH and FSH synthesis, respectively, by a mechanism including secreted factors. Conclusion: Different G proteins and autocrine signaling regulate the pattern of FSH and LH expression by GnRH. Significance: A novel G protein and autocrine signaling mechanism has been identified.

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Section: Discussionmentioning

confidence: 97%

G Proteins and Autocrine Signaling Differentially Regulate Gonadotropin Subunit Expression in Pituitary Gonadotrope

Choi¹,

Jia²,

Pfeffer³

et al. 2012

Journal of Biological Chemistry

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“…There is also a connection between G s and G q/11 signaling and Fsh␤ expression. CREB serves to integrate signals for basal-and GnRH-stimulated transcription of the rat FSH␤ gene (37), and the GnRH-responsive element contains a partial CRE site that binds CREB. Others have shown that GnRH induces binding of the AP-1 complex to the Fsh␤ promoter, and mutation of the AP-1 site reduces GnRH induction (33).…”

Section: Discussionmentioning

confidence: 99%

Signaling Responses to Pulsatile Gonadotropin-releasing Hormone in LβT2 Gonadotrope Cells

Tsutsumi

Mistry

Webster

2010

Journal of Biological Chemistry

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The hypothalamic neuropeptide gonadotropin-releasing hormone (GnRH) is secreted in a pulsatile fashion by hypothalamic neurons, and alterations in pulse frequency and amplitude differentially regulate gonadotropin synthesis and release. In this study, we investigated the kinetics of G s and G q signaling in response to continuous or pulsatile GnRH using fluorescence resonance energy transfer reporters in live mouse L␤T2 gonadotrope cells. cAMP and protein kinase A-dependent reporters showed a rapid but transient increase in fluorescence resonance energy transfer signal with increasing doses of constant GnRH, and in contrast diacylglycerol (DAG) and calcium reporters showed a rapid and sustained signal. Multiple pulses of GnRH caused multiple pulses of cAMP and protein kinase A activation without desensitization, but the DAG and calcium reporters were rapidly desensitized resulting in inhibition of calcium and DAG responses. At the transcriptional level, both a cAMPdependent cAMP-response element reporter and a DAG/ calcium-dependent AP-1 reporter showed a pulse frequencydependent increase in luciferase activity. However, constant GnRH stimulation gave very little cAMP-response element activation but very strong AP-1 activation. Based on these data, we propose that both the GnRH-R-G s and G q pathways are responsive to pulses of GnRH, but only the G q pathway is responsive to constant GnRH. Furthermore, the G q pathway is subject to desensitization with multiple GnRH pulses, but the G s pathway is not.The hypothalamic hormone gonadotropin-releasing hormone (GnRH) 2 is the central regulator of the mammalian reproduction system. It acts in the anterior pituitary via a specific GnRH receptor (GnRH-R) on the plasma membrane of gonadotrope cells where it triggers the synthesis and secretion of LH and FSH, which in turn regulate production of gonadal steroids and reproduction (1, 2). Physiologically, GnRH is secreted in a pulsatile fashion by hypothalamic neurons (2). Gonadotrope responsiveness is modulated by both the GnRH concentration and by the frequency or pattern of its administration. During the female reproductive cycle, estrogen increases the GnRH pulse frequency and amplitude during the pre-ovulatory phase resulting in the LH surge and ovulation. Progesterone then slows and diminishes the hypothalamic GnRH pulses resulting in a preferential increase in FSH to stimulate the next round of follicle development (3). How the gonadotrope responds to the different pulse frequencies and amplitude to differentially produce LH or FSH is poorly understood.

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“…Introduced mutation of the E-BOX sequence was based on a previous work of Ciccone et al (35). For mutagenesis, the following primer pairs were used: 59-TCCACAGGGTGTACGGTAGCACATGCCACCACC-39 (m4f) and 59-GGTGGTGGCATGTGCTACCGTACACCCTGTGGA-39 (m4r); 59-GTCCCTGAAGTACCCTAGCAAAGAGGGTCAGGC-39 (m3f) and 59-GCCTGACCCTCTTTGCTAGGGTACTTCAGGGAC-39 (m3r); 59-CCC-AGATTGGCACCGTAGGGCGCCTGTCATCCT-39 (m2f) and 59-AGGA-TGACAGGCGCCCTACGGTGCCAATCTGGG-39 (m2r); and 59-GGTG-GGGGGTTGTACCTTAGCCACCTGTGTGGT-39 (m1f) and 59-ACCAC-ACAGGTGGCTAAGGTACAACCCCCCACC-39 (m1r).…”

Section: Site-directed Mutagenesismentioning

confidence: 99%

Upstream Stimulating Factors Regulate the Expression of RORγT in Human Lymphocytes

Ratajewski

Walczak‐Drzewiecka

Sałkowska

et al. 2012

The Journal of Immunology

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Retinoic acid-related orphan receptor γT (RORγT) is the orphan nuclear receptor that regulates the development of Th17 cells and the expression of IL-17. The differentiation of Th17 cells is associated with the upregulation of RORγT mRNA, and the mechanisms regulating that process in human cells are not well understood. We investigated the transcriptional regulation of RORγT in a human lymphocytic cell line and Th17 differentiated from naive CD4+ cells from human peripheral blood. A series of experiments, including 5′ deletion and in situ mutagenesis analysis of the human RORγT promoter, chromatin immunoprecipitation, and overexpression of selected transcription factors, revealed that the transcription factors upstream stimulatory factor 1 (USF-1) and USF-2 are indispensable for the transcription of RORγT in human lymphocytes. There was also upregulation of USF-1 and USF-2 during the differentiation of Th17 cells from naive CD4+ cells. In this article, we report the first analysis, to our knowledge, of the human RORγT promoter and demonstrate the role of the USF-1 and USF-2 transcription factors in regulating the expression of RORγT in human lymphocytes. Thus, USFs are important for the molecular mechanisms of Th17 differentiation, and possible changes in the expression of USFs might be of interest for inflammatory conditions with a Th17 component. Furthermore, these observations suggest a possible link between metabolic disorders in which the role of glucose-induced USF expression has already been established and autoimmune diseases in which the upregulation of RORγT is frequently detected.

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A Composite Element that Binds Basic Helix Loop Helix and Basic Leucine Zipper Transcription Factors Is Important for Gonadotropin-Releasing Hormone Regulation of the Follicle-Stimulating Hormone β Gene

Cited by 41 publications

References 59 publications

G Proteins and Autocrine Signaling Differentially Regulate Gonadotropin Subunit Expression in Pituitary Gonadotrope

G Proteins and Autocrine Signaling Differentially Regulate Gonadotropin Subunit Expression in Pituitary Gonadotrope

Signaling Responses to Pulsatile Gonadotropin-releasing Hormone in LβT2 Gonadotrope Cells

Upstream Stimulating Factors Regulate the Expression of RORγT in Human Lymphocytes

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