Tissue-specific gene expression in the pituitary: the glycoprotein hormone alpha-subunit gene is regulated by a gonadotrope-specific protein.

Horn, Friedemann; Windle, Jolene J.; Barnhart, Kerry M.; Mellon, Pamela L.

doi:10.1128/mcb.12.5.2143

Cited by 120 publications

(93 citation statements)

References 57 publications

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“…By later stages of pituitary development and in adult mammals, ␣GSU expression is limited to thyrotropes and gonadotropes (4). Gonadotrope-specific expression of the ␣GSU gene is controlled by an array of regulatory elements, including the pituitary glycoprotein hormone basal element (5,6), ␣ basal elements (6), gonadotrope-specific element (7), and tandemly repeated cAMP response elements (8 -10), as well as the intricate interplay between their cognate binding proteins (6).…”

mentioning

confidence: 99%

Embryonic Expression of the Luteinizing Hormone β Gene Appears to Be Coupled to the Transient Appearance of p8, a High Mobility Group-related Transcription Factor

Quirk

Seachrist

Nilson

2003

Journal of Biological Chemistry

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A comparison between two pituitary-derived cell lines (␣T3-1 and L␤T2) that represent gonadotropes at early and late stages of development, respectively, was performed to further elucidate the genomic repertoire required for gonadotrope specification and luteinizing hormone ␤ (LH␤) gene expression. One isolated clone that displayed higher expression levels in L␤T2 cells encodes p8, a high mobility group-like protein with mitogenic potential that is up-regulated in response to proapoptotic stimuli and in some developing tissues. To test the functional significance of this factor in developing gonadotropes, a knockdown of p8 in L␤T2 cells was generated. The loss of p8 mRNA correlated with loss of endogenous LH␤ mRNA and the loss of activity of a transfected LH␤ promoter-driven reporter, even upon treatment with gonadotropin-releasing hormone. In addition, expression of p8 mRNA in developing mouse pituitary glands mirrored its expression in the gonadotrope-derived cell lines and coincided with the first detectable appearance of LH␤ mRNA. In contrast, p8 mRNA was undetectable in the pituitary glands of normal adults. Taken together, our data indicate that p8 is a stage-specific component of the gonadotrope transcriptome that may play a functional role in the initiation of LH␤ gene expression during embryonic cellular differentiation.With its ability to stimulate gonadal steroidogenesis and gametogenesis, luteinizing hormone (LH) 1 is essential for normal reproductive function in mammals (1, 2). Luteinizing hormone is a heterodimeric protein composed of an ␣ glycoprotein hormone subunit (␣GSU) common to all members of the glycoprotein family of hormones that is non-covalently linked to a unique LH␤ subunit that confers its biological specificity (1, 2). Biosynthesis of LH depends on the coordinated expression of both the ␣GSU and LH␤ subunit genes. In humans, the single copy ␣GSU gene resides on chromosome 6q12-q21 (Locus ID 1081) while the LH␤ gene resides amid a cluster of six chorionic gonadotropin-␤ genes on chromosome 19q13.32 (Locus ID 1082). In addition to their different locations within the human genome, the pattern of expression of the genes encoding ␣GSU and LH␤ are temporally and spatially distinct.During development ␣GSU is seen throughout Rathke's pouch as early as embryonic day (e) 9.5 in the mouse (3). By later stages of pituitary development and in adult mammals, ␣GSU expression is limited to thyrotropes and gonadotropes (4). Gonadotrope-specific expression of the ␣GSU gene is controlled by an array of regulatory elements, including the pituitary glycoprotein hormone basal element (5, 6), ␣ basal elements (6), gonadotrope-specific element (7), and tandemly repeated cAMP response elements (8 -10), as well as the intricate interplay between their cognate binding proteins (6).In a fashion similar to the ␣GSU promoter, the LH␤ gene is regulated by a combinatorial array of transcription factors and regulatory elements. In this case, however, the elements consist of those that bind early growth response ...

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mentioning

confidence: 99%

Embryonic Expression of the Luteinizing Hormone β Gene Appears to Be Coupled to the Transient Appearance of p8, a High Mobility Group-related Transcription Factor

Quirk

Seachrist

Nilson

2003

Journal of Biological Chemistry

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“…Binding to the mouse GSE was shown to be specific since it could be reduced significantly in the presence of antibody to mouse SF-1 and excess non-biotinylated GSE. It has been reported previously that the introduction of two C to T mutations in the mouse GSE oligonucleotide (termed GSE  ) eliminates the binding of SF-1 in both South Western blotting and gel retardation experiments (Horn et al 1992, Barnhart & Mellon 1994. These studies were performed using the GSE of the human -subunit promoter and nuclear extracts from T3-1 cells.…”

Section: Discussionmentioning

confidence: 99%

“…SF-1 is also known as adrenal-4-binding protein (Ad4bP) and gonadotroph-specific element binding protein 1 (GSE-B1) (Morohashi et al 1992, Horn et al 1992. It was revealed by cloning to be highly homologous to members of the nuclear receptor family, especially in the zinc-finger DNA-binding domain (Laudet et al 1992, Wong et al 1996.…”

Section: Introductionmentioning

confidence: 99%

“…The gp -SU gene is the common element in this family of glycoprotein hormones and is the earliest of the hormone genes to be expressed in the developing mouse pituitary (Simmons et al 1990, Japon et al 1994. Expression of the -subunit gene in pituitary gonadotrophs involves a gonadotroph specific element (GSE), conserved in all mammalian -subunit genes, which has been shown to bind to SF-1 in T3-1 cells (a mouse clonal gonadotroph cell line) (Horn et al 1992, Barnhart & Mellon 1994. However relatively little is known about the molecular mechanisms involved in the control and expression of the SF-1 gene in the gonadotroph or of the regulation by SF-1 of gonadotroph-specific genes.…”

Section: Introductionmentioning

confidence: 99%

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Steroidogenic factor 1-DNA binding: a kinetic analysis using surface plasmon resonance

Bryan

Aylwin²,

Newman³

et al. 1999

Journal of Molecular Endocrinology

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Basal expression of the glycoprotein hormone alpha-subunit gene in pituitary gonadotrophs is partially dependent on a gonadotroph specific element (GSE) which binds the nuclear receptor, steroidogenic factor-1 (SF-1). We have used surface plasmon resonance (SPR) to determine the association (kappa ass), dissociation (kappa diss) and affinity (KA) constants of SF-1 binding to immobilized oligonucleotides containing either the GSE consensus motif or a GSE mutant with a 2 bp substitution in the GSE site (GSEMUT). In vitro translated SF-1 protein bound the consensus GSE with a threefold increase in affinity constant (P<0.01) compared with the GSEMUT. This was due primarily to a significant increase (P<0.05) in the kappa ass for SF-1 to the GSE and a slower kappa diss (P<0.05). The binding interaction was specific and could be significantly inhibited (P<0. 001) by either anti-SF-1 antibody or excess non-biotinylated GSE. The addition of 14 bp wild-type flanking sequences significantly reduced the affinity of SF-1 to both the GSE (P<0.05) and the GSEMUT (P<0.01). This was due to a significant (P<0.01) decrease in kappa ass for the wild-type and mutant long oligonucleotides compared with the short GSE. Nuclear extracts from alphaT3-1 gonadotroph cells also bound the GSE and GSEMUT, giving kappa diss values which were two- to threefold slower than those obtained with in vitro translated SF-1. Thus, SPR is a powerful technique for examining kinetic interaction between SF-1 and its binding site, and is able to demonstrate the effects of mutations and flanking sequences on that interaction.

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“…SF-1 regulates the expression of GSU and LH (Barnhart & Mellon 1994, Ingraham et al 1994, Halvorson et al 1996 along with the GnRH receptor (GnRH-R) (Duval et al 1997), neuronal nitric oxide synthase (nNOS) (Wei et al 2002) and the inhibin gene (Ito et al 2000). Highly conserved SF-1 response elements reside within the promoter regions of these genes, termed gonadotroph-specific elements (GSEs) (Horn et al 1992). The GSE of the GSU gene was found to specifically bind SF-1 by the Ingraham and Mellon groups in 1994 (Ingraham et al 1994, Barnhart & Mellon 1994.…”

Section: Sf-1 Target Genesmentioning

confidence: 99%

Steroidogenic factor-1: a key regulator of gonadotroph gene expression

Fowkes

Burrin²

2003

Journal of Endocrinology

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Tissue-specific gene expression in the pituitary: the glycoprotein hormone alpha-subunit gene is regulated by a gonadotrope-specific protein.

Cited by 120 publications

References 57 publications

Embryonic Expression of the Luteinizing Hormone β Gene Appears to Be Coupled to the Transient Appearance of p8, a High Mobility Group-related Transcription Factor

Embryonic Expression of the Luteinizing Hormone β Gene Appears to Be Coupled to the Transient Appearance of p8, a High Mobility Group-related Transcription Factor

Steroidogenic factor 1-DNA binding: a kinetic analysis using surface plasmon resonance

Steroidogenic factor-1: a key regulator of gonadotroph gene expression

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