Autocrine/paracrine regulation of pituitary function by activin, inhibin and follistatin

Bilezikjian, Louise M.; Blount, Amy L.; Leal, Ângela M. O.; Donaldson, Cindy; Fischer, Wolfgang; Vale, Wylie

doi:10.1016/j.mce.2004.02.010

Cited by 150 publications

(105 citation statements)

References 94 publications

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“…A previous study also localized FoxL2 to LH␤-positive cells of the embryonic pituitary (56). These findings highlight the likelihood that FoxL2 and follistatin co-localize, given that gonadotropes also express follistatin (24,30 FoxL2 expression in FS/D1h folliculostellate cells, which lack FoxL2 and fail to show activin-dependent regulation of follistatin (26 -29), would also enable SBE1-dependent follistatin transcription. These observations suggest that, whereas Smad3 is the essential mediator of activin via SBE1, FoxL2 must somehow be functionally or physically engaged with Smad3 to facilitate the actions of activin/Smad3 within the context of this intronic regulatory region of the follistatin gene.…”

Section: Discussionsupporting

confidence: 55%

FoxL2 and Smad3 Coordinately Regulate Follistatin Gene Transcription

Blount

Schmidt

Justice

et al. 2009

Journal of Biological Chemistry

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101

118

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Follistatin is a transcriptional target and a modulator of activin action. Through an autocrine/paracrine loop, activin controls follistatin levels and thus regulates its own bioavailability. In gonadotropic ␣T3-1 cells, activin induces follistatin transcription primarily through the action of Smad3 at an intronic Smad-binding element (SBE1). Using a proteomics approach, we searched for endogenous ␣T3-1 proteins that participate in SBE1-mediated transcription. We identified

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Section: Discussionsupporting

confidence: 55%

FoxL2 and Smad3 Coordinately Regulate Follistatin Gene Transcription

Blount

Schmidt

Justice

et al. 2009

Journal of Biological Chemistry

Self Cite

101

118

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“…We next studied inhibin which is a heterodimeric peptide hormone produced in the ovary that inhibits FSH synthesis in the pituitary. Inhibin␣ subunit interacts with the activin type I receptor, antagonizes the activin signaling in the pituitary gonadotrope (35), and has been reported to be regulated by GnRH in the gonadotrope (36,37). Therefore, we tested whether inhibin␣ expression could be regulated by GnRH stimulation in a G␣ sdependent manner.…”

Section: G␣ S -Dependent Fsh␤ Mrna Suppression Is Mediated Bymentioning

confidence: 99%

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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“…Activins selectively regulate FSH production and secretion from gonadotrope cells (Bilezikjian et al 2004, Gregory & Kaiser 2004. The ligands are members of the TGFB superfamily and come in three forms through the disulfide linking of two related subunits: activin A (INHBA-INHBA), activin B (INHBB-INHBB), and activin AB (INHBA-INHBB).…”

Section: Introductionmentioning

confidence: 99%

Acute regulation of murine follicle-stimulating hormone β subunit transcription by activin A

Lamba¹,

Santos²,

Philips³

et al. 2006

Journal of Molecular Endocrinology

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In rodents, activins stimulate immediate-early increases in pituitary follicle-stimulating hormone (Fshb) subunit transcription. Here, we investigated the underlying signaling mechanisms using the mouse gonadotrope cell line, L T2. Activin A increased mouse Fshb-luciferase reporter activity within 4 h through a Smad-dependent signaling pathway. The ligand rapidly stimulated formation of SMAD2/3/4 complexes that could interact with a consensus palindromic Smad binding element (SBE) in the proximal Fshb promoter. SMAD over-expression potently stimulated transcription, with the combination of SMADs 2, 3 and 4 producing the greatest synergistic activation. A mutation in the SBE that abolished Smad binding greatly impaired the effects of acute (4 h) activin A treatment and SMAD over-expression on promoter activity, but did not abolish the effects of chronic (24 h) activin A exposure. Within activated SMAD complexes, SMADs 3 and 4 appeared to bind the SBE simultaneously and the binding of both was required for maximal transcriptional activation. Interestingly, the human FSHB promoter, which lacks the consensus SBE, was neither rapidly stimulated by activin A nor by over-expressed SMADs, but was activated by 24 h activin A. Addition of the SBE to the human promoter increased both SMAD2/3/4-sensitivity and acute regulation by activin A, though not to levels observed in mouse. We postulate that short reproductive cycles in female rodents, particularly the brief interval between the primary and secondary FSH surges of the estrous cycle, require the Fshb promoter in these animals to be particularly sensitive to the rapid, Smad-dependent actions of activins on transcription. The human FSHB promoter, in contrast, is chronically regulated by activins seemingly through a SMAD-independent pathway.

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Autocrine/paracrine regulation of pituitary function by activin, inhibin and follistatin

Cited by 150 publications

References 94 publications

FoxL2 and Smad3 Coordinately Regulate Follistatin Gene Transcription

FoxL2 and Smad3 Coordinately Regulate Follistatin Gene Transcription

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

Acute regulation of murine follicle-stimulating hormone β subunit transcription by activin A

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