Differential Regulation of Gonadotropin Subunit Messenger Ribonucleic Acids by Gonadotropin-Releasing Hormone Pulse Frequency in Ewes

Leung, Kwanyee; Kaynard, Alan H.; Negrini, Bryan P.; Kim, Kyoon Eon; Maurer, Richard A.; Landefeld, Thomas D.

doi:10.1210/mend-1-10-724

Cited by 65 publications

(22 citation statements)

References 35 publications

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“…However, subsequent analysis of the factors that were isolated in the screen demonstrated that none of the LIM-binding factors were dependent on NLI for binding. The bait and cDNA library plasmids were transformed into the L40 yeast strain (MATa his3⌬200 trp1-901 leu2-3, 112 ade2 LYS2:: (lexAop) 4 -His3 URA3::(lexAop) 8 -lacZ GAL4 gal80) (37) and selected for positive, interacting clones using histidine minus medium in the presence of 30 mM 3-aminotriazole to suppress the background activity of the bait. Further selection was performed on histidine minus medium containing 50 mM 3-aminotriazole.…”

Section: Methodsmentioning

confidence: 99%

MRG1 Binds to the LIM Domain of Lhx2 and May Function as a Coactivator to Stimulate Glycoprotein Hormone α-Subunit Gene Expression

Glenn¹,

Maurer

1999

Journal of Biological Chemistry

Self Cite

102

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Members of the LIM homeodomain family of transcription factors have been shown to contribute to the regulated expression of the ␣-subunit of the glycoprotein family of hormones (1). The ability of the pituitary to secrete the gonadotropic hormones, follicle-stimulating hormone, and luteinizing hormone is crucial for normal reproductive function. The synthesis and secretion of the gonadotropins is regulated by the hypothalamic hormone, gonadotropin-releasing hormone (GnRH), 1 which acts to increase gonadotropin subunit mRNA levels (2-9) through effects at the transcriptional level (10, 11).LIM homeodomain factors appear to play a role in both basal and GnRH-stimulated expression of the glycoprotein hormone ␣-subunit gene (1, 12). Initial studies demonstrated that LIM homeodomain factor-2 (Lhx2, also designated LH-2) can bind to a pituitary-specific enhancer element designated the PGBE of the mouse ␣-subunit gene (1). Because both the PGBE and a separate, structurally distinct DNA element designated the GnRH-RE are required for GnRH responsiveness of the mouse glycoprotein hormone ␣-subunit promoter (12), the finding that Lhx2 binds to the PGBE implies that this LIM factor plays a role in transcriptional responses to GnRH. It has also been shown that a related LIM factor, Lhx3 (also designated pLIM or LIM3) can also enhance ␣-subunit gene expression (13). Targeted disruption of the Lhx3 gene in mouse results in loss of pituitary organogenesis (14), demonstrating that LIM factors also play an important developmental role in the formation of the pituitary.The specific role that the LIM domains play in transcriptional activation is somewhat unclear. The LIM domain, named for the genes of the first three members of the family, lin-11 (15), isl-1 (16), and mec-3 (17), is characterized by the presence of two zinc finger motifs that involve cysteine and histidine or aspartate residues that tetrahedrally coordinate a zinc atom (18,19). There is evidence that some LIM domains can inhibit DNA binding of the associated homeodomain (20 -22). This would suggest that the LIM domain may negatively regulate LIM factor activity. However, it is not clear that inhibition of DNA binding is a general phenomenon for LIM factors (23). Functional studies of Xlim-1 in Xenopus laevis have shown that deletion or mutation of the LIM domain of Xlim-1 results in the induction of secondary axis formation, whereas the wild type factor has no effect (24). This has been interpreted as evidence for a negative role for the LIM domain in regulating transcription. However, in the absence of more mechanistic information about Xlim-1 action, other interpretations are possible. In contrast to the view that LIM domains play a negative role in regulating DNA binding and transcription, some LIM factors have been shown to demonstrate synergistic transcriptional activation with other transcription factors (13,25).Recently, a putative co-activator was identified independently in several labs that binds to members of the LIM homeodomain protein family and nucle...

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Section: Methodsmentioning

confidence: 99%

MRG1 Binds to the LIM Domain of Lhx2 and May Function as a Coactivator to Stimulate Glycoprotein Hormone α-Subunit Gene Expression

Glenn¹,

Maurer

1999

Journal of Biological Chemistry

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102

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“…Lesions of either the medial basal hypothalamus or the arcuate nucleus also eradicate LH pulses (1). By comparison, continuous infusion of LHRH, which desensitizes the gonadotropes through down-regulation of the LHRH receptor (14), also abolishes episodic secretion of LH and reduces LH 03-and a-subunit mRNA levels (15,16). While the relationship between LHRH and LH secretion is well established, it is unclear whether the generator for LHRH pulses is located within the LHRH neuronal network itself or within networks of other neighboring neurons or cells that directly affect LHRH secretion.…”

mentioning

confidence: 99%

Intrinsic pulsatile secretory activity of immortalized luteinizing hormone-releasing hormone-secreting neurons.

Wetsel

Valênça

Merchenthaler

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

260

130

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Mammalian reproduction is dependent upon intermittent delivery of luteinizing hormone-releasing hormone (LHRH) to the anterior pituitary. This mode of secretion is required to sensitize maximally the gonadotrophs to LHRH stimulation and to regulate gonadotropin gene expression. While LHRH secretion is pulsatile in nature, the origin of the pulse generator is unknown. In this report, we show that this oscillator could be located within the LHRH neuronal network. When immortalized LHRH neurons are placed into a perifusion system, LHRH is secreted into the medium in a pulsatile fashion under basal conditions. LHRH secretion and the number of LHRH pulses are reduced when calcium is removed from the medium. Perifusion also influences pro-LHRH processing, since the molar ratio of its processed products varies dramatically when the cells are transferred from a static system. Several different cellular mechanisms may underlie these changes in secretion and processing. Lucifer yellow experiments reveal that some cells are dye-coupled. Hence, these cells could be electrically coupled through gap junctions such that secretion from individual cells could be coordinated. Secretion could also be synchronized through the observed synapse-like contacts. These contacts could perform a negative-feedback role to regulate not only the amount of LHRH released but also the molecular forms secreted. The organization of LHRH neurons into interconnected clusters could serve to coordinate LHRH secretion from individual cells and, thereby, orchestrate functions in vivo as diverse as the onset of puberty, the timing of ovulation, and the duration of lactational infertility.Luteinizing hormone (LH)-releasing hormone (LHRH) is a major regulator of reproduction in mammals (1-3). While LHRH neuronal cell bodies are scattered throughout the anterior hypothalamic region, their nerve terminals converge on the median eminence. LHRH is secreted into the hypophysial portal circulation, where it is transported to the anterior pituitary to stimulate the release of LH and folliclestimulating hormone.In all mammalian species studied so far, secretion of LH into blood is episodic in nature (1,(4)(5)(6)(7)(8). Interestingly, LHRH is secreted into the hypophysial portal blood in a pulsatile manner (9-11), and LH pulses are preceded by LHRH release (1, 10, 11). In addition, LH pulsatile secretion is lost either after passive immunization with LHRH antiserum (12) or with administration of a LHRH antagonist (13). Lesions of either the medial basal hypothalamus or the arcuate nucleus also eradicate LH pulses (1). By comparison, continuous infusion of LHRH, which desensitizes the gonadotropes through down-regulation of the LHRH receptor (14), also abolishes episodic secretion of LH and reduces LH 03-and a-subunit mRNA levels (15, 16). While the relationship between LHRH and LH secretion is well established, it is unclear whether the generator for LHRH pulses is located within the LHRH neuronal network itself or within networks of other neighboring neuro...

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“…[14] used the same animal model to demonstrate that the frequency of the pulsatile GnRH stimulus regulates LHp and a-subunit mRNA levels. In ovariectomized (OVX), progesterone-replaced sheep, the frequency of adminis tration of GnRH regulated mRNA levels of all three gonadotro pin subunits, with LHp and FSHp responding similarly, and a-subunit being regulated differently [24], Nilson et al [28] …”

mentioning

confidence: 99%

Regulation of Follicle-Stimulating Hormone β and Common α-Subunit Messenger Ribonucleic Acid by Gonadotropin-Releasing Hormone and Estrogen in the Sheep Pituitary

et al. 1989

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The effect of gonadotropin-releasing hormone (GnRH) and/or estradiol (E₂) on pituitary messenger ribonucleic acid (mRNA) levels of luteinizing hormone β (LHβ), follicle-stimulating hormone β (FSHβ) and the common α-subunit were determined in anterior pituitary glands from ovariectomized (OVX) ewes. Hypothalamo-pituitary disconnected (HPD) ewes receiving appropriate hormonal treatment were used to assess the relative roles of GnRH and E₂ in directly regulating FSHβ and α-subunit mRNA levels. Levels of LHβ mRNA were increased in OVX animals compared with intact controls, and E₂ treatment of OVX animals significantly reduced mRNA levels of LHβ and FSHβ. HPD substantially reduced FSHβ and α-subunit mRNA levels. Treatment of OVX/HPD animals with pulses of GnRH (250 ng/2 h) for 1 week restored FSHβ and α-subunit mRNA to OVX levels. Combined GnRH and E₂ treatment significantly lowered FSHβ mRNA levels, but resulted in a rise in α-subunit mRNA levels. Treatment of OVX/HPD ewes with E₂ alone had no effect on FSHβ and α-subunit mRNA levels. These findings indicate that E₂ acts directly on the pituitary to negatively regulate FSHβ mRNA levels, and to positively regulate α-subunit mRNA levels in the presence of GnRH.

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Differential Regulation of Gonadotropin Subunit Messenger Ribonucleic Acids by Gonadotropin-Releasing Hormone Pulse Frequency in Ewes

Cited by 65 publications

References 35 publications

MRG1 Binds to the LIM Domain of Lhx2 and May Function as a Coactivator to Stimulate Glycoprotein Hormone α-Subunit Gene Expression

MRG1 Binds to the LIM Domain of Lhx2 and May Function as a Coactivator to Stimulate Glycoprotein Hormone α-Subunit Gene Expression

Intrinsic pulsatile secretory activity of immortalized luteinizing hormone-releasing hormone-secreting neurons.

Regulation of Follicle-Stimulating Hormone β and Common α-Subunit Messenger Ribonucleic Acid by Gonadotropin-Releasing Hormone and Estrogen in the Sheep Pituitary

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