Regulation of gonadotropin-releasing hormone-1 gene transcription by members of the purine-rich element-binding protein family

Zhao, Sheng; Kelm, Robert J.; Fernald, Russell D.

doi:10.1152/ajpendo.00597.2009

Cited by 8 publications

(3 citation statements)

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“…One study seeking to identify novel DNA-binding proteins for gonadotropin-releasing hormone 1 ( GNRH1 ) promoter, identified both Purα and Purβ as potential regulators of GNRH1 gene expression. 38 Subsequent in vivo studies have confirmed binding of both Purα and Purβ to the upstream region of the GNRH1 gene. While overexpression of Purβ was shown to significantly downregulate GNRH1 expression in transiently transfected mouse GT1-7 cells, this could not be demonstrated for Purα.…”

Section: Discussionmentioning

confidence: 97%

Whole exome sequencing in family trios revealsde novomutations inPURAas a cause of severe neurodevelopmental delay and learning disability

et al. 2014

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BackgroundDe novo mutations are emerging as an important cause of neurocognitive impairment, and whole exome sequencing of case-parent trios is a powerful way of detecting them. Here, we report the findings in four such trios.MethodsThe Deciphering Developmental Disorders study is using whole exome sequencing in family trios to investigate children with severe, sporadic, undiagnosed developmental delay. Three of our patients were ascertained from the first 1133 children to have been investigated through this large-scale study. Case 4 was a phenotypically isolated case recruited into an undiagnosed rare disorders sequencing study.ResultsProtein-altering de novo mutations in PURA were identified in four subjects. They include two different frameshifts, one inframe deletion and one missense mutation. PURA encodes Pur-α, a highly conserved multifunctional protein that has an important role in normal postnatal brain development in animal models. The associated human phenotype of de novo heterozygous mutations in this gene is variable, but moderate to severe neurodevelopmental delay and learning disability are common to all. Neonatal hypotonia, early feeding difficulties and seizures, or ‘seizure-like’ movements, were also common.Additionally, it is suspected that anterior pituitary dysregulation may be within the spectrum of this disorder. Psychomotor developmental outcomes appear variable between patients, and we propose a possible genotype–phenotype correlation, with disruption of Pur repeat III resulting in a more severe phenotype.ConclusionsThese findings provide definitive evidence for the role of PURA in causing a variable syndrome of neurodevelopmental delay, learning disability, neonatal hypotonia, feeding difficulties, abnormal movements and epilepsy in humans, and help clarify the role of PURA in the previously described 5q31.3 microdeletion phenotype.

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Section: Discussionmentioning

confidence: 97%

Whole exome sequencing in family trios revealsde novomutations inPURAas a cause of severe neurodevelopmental delay and learning disability

et al. 2014

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“…cDNA was diluted two-fold in nuclease-free water for use in qRT-PCR. Primer sets for all genes were commercially synthesized (Invitrogen) and identical to those used previously for A. burtoni : CRF , CRF 1 , CRF 2 , CRF binding protein ( CRFbp ) [48] ; g3pdh , 18s rRNA [49] ; LHβ , FSHβ [29] , [50] ; and GnRH1 [51] , [52] . Each primer pair produced a single melting curve peak in the presence of cDNA template, and showed no or late amplification when water was used as a template in the reaction mix.…”

Section: Methodsmentioning

confidence: 99%

Social Opportunity Rapidly Regulates Expression of CRF and CRF Receptors in the Brain during Social Ascent of a Teleost Fish, Astatotilapia burtoni

et al. 2014

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In social animals, hierarchical rank governs food availability, territorial rights and breeding access. Rank order can change rapidly and typically depends on dynamic aggressive interactions. Since the neuromodulator corticotrophin releasing factor (CRF) integrates internal and external cues to regulate the hypothalamic-pituitary adrenal (HPA) axis, we analyzed the CRF system during social encounters related to status. We used a particularly suitable animal model, African cichlid fish, Astatotilapia burtoni, whose social status regulates reproduction. When presented with an opportunity to rise in rank, subordinate A. burtoni males rapidly change coloration, behavior, and their physiology to support a new role as dominant, reproductively active fish. Although changes in gonadotropin-releasing hormone (GnRH1), the key reproductive molecular actor, have been analyzed during social ascent, little is known about the roles of CRF and the HPA axis during transitions. Experimentally enabling males to ascend in social rank, we measured changes in plasma cortisol and the CRF system in specific brain regions 15 minutes after onset of social ascent. Plasma cortisol levels in ascending fish were lower than subordinate conspecifics, but similar to levels in dominant animals. In the preoptic area (POA), where GnRH1 cells are located, and in the pituitary gland, CRF and CRF1 receptor mRNA levels are rapidly down regulated in ascending males compared to subordinates. In the Vc/Vl, a forebrain region where CRF cell bodies are located, mRNA coding for both CRFR1 and CRFR2 receptors is lower in ascending fish compared to stable subordinate conspecifics. The rapid time course of these changes (within minutes) suggests that the CRF system is involved in the physiological changes associated with shifts in social status. Since CRF typically has inhibitory effects on the neuroendocrine reproductive axis in vertebrates, this attenuation of CRF activity may allow rapid activation of the reproductive axis and facilitate the transition to dominance.

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“…DUSP1 has also been observed in luteinizing hormone beta (LHb) subunit gene expression in gonadotrophs (Purwana, Kanasaki, Oride, & Miyazaki, 2010). A few studies in the mouse neuronal GT1-7 cells suggest that enhanced occupancy of GnRH 1 gene upstream promoter by a transcription factor purine-rich element-binding protein (PURA) downregulated GnRH 1 mRNA levels, suggesting PURA as a repressor of GnRH1 gene transcription (Zhao, Kelm Jr., Fernald, 2010). We note that migratory juncos showed higher level of PURA protein than residents, which could be related to delay in their reproduction.…”

Section: Endocrine Signaling Associated With Earlier Timing Of Reproduction In Resident Juncos-mentioning

confidence: 99%

Comparative proteomics reveals molecular correlates of population-level variation in reproductive timing in a North American songbird

Singh¹,

Fudickar²,

Smiley³

et al. 2020

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Individuals and populations time annual events such as migration and reproduction to match favorable times in their environment. Physiological preparations for reproduction rely on predictive cues such as day length to accurately time reproduction. In birds, preparation typically begins with light reception by the hypothalamus, which initiates multiple central and peripheral responses. We studied two closely related populations of a songbird, the dark-eyed junco, that live in a common winter environment but diverge in their timing of reproduction as spring approaches. One population is resident and initiates reproduction earlier than the other, which migrates northward prior to reproducing. We caught resident and migrant juncos from the field during early spring and collected hypothalamic and pituitary tissues. We used isobaric tandem mass tag (TMT) labeling to identify differentially expressed proteins (DEPs) as possible regulators of the seasonal divergence in reproductive timing. We found 3038 unique proteins expressed in the hypothalamus and pituitary proteome, among which we identified 75 DEPs.These were associated with hormones, neurotransmitter secretion, transport, neuropeptide synthesis, prohormone synthesis, neurogenesis, GnRH synthesis, release and stability, food intake, locomotion, and social behavior. Some of these proteins were associated with early breeding in resident juncos, and others were associated with increased food intake, fat metabolism, locomotor activity and phenology in migratory juncos. Our results provide new insight into the neuroendocrine regulation of the timing of reproduction and migration. This study provides the first evidence of a relationship between functional protein variation in the neuroendocrine tissues and seasonal divergence in reproductive timing.

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Regulation of gonadotropin-releasing hormone-1 gene transcription by members of the purine-rich element-binding protein family

Abstract: Zhao S, Kelm RJ Jr, Fernald RD. Regulation of gonadotropinreleasing hormone-1 gene transcription by members of the purinerich element-binding protein family. Am J Physiol Endocrinol Metab 298: E524 -

Cited by 8 publications

References 88 publications

Whole exome sequencing in family trios revealsde novomutations inPURAas a cause of severe neurodevelopmental delay and learning disability

Whole exome sequencing in family trios revealsde novomutations inPURAas a cause of severe neurodevelopmental delay and learning disability

Social Opportunity Rapidly Regulates Expression of CRF and CRF Receptors in the Brain during Social Ascent of a Teleost Fish, Astatotilapia burtoni

Comparative proteomics reveals molecular correlates of population-level variation in reproductive timing in a North American songbird

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