Gonadotropin-Releasing Hormone (GnRH) Positively Regulates Corticotropin-Releasing Hormone-Binding Protein Expression via Multiple Intracellular Signaling Pathways and a Multipartite GnRH Response Element in αT3-1 Cells

Westphal, Nicole J.; Seasholtz, Audrey F.

doi:10.1210/me.2004-0519

Cited by 13 publications

(7 citation statements)

References 58 publications

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“…Five micrograms of DNased RNA was used for first-strand cDNA synthesis using random hexamer primers and Superscript II reverse transcriptase (Invitrogen). PCR reactions (25μl) contained 1 or 2μl cDNA template (female and male, respectively), 12.5μl 2xSYBR Green I Master Mix (Bio-Rad Laboratories, Inc., Hercules, CA), and 250nM forward and reverse primers for mCRH-BP or TATA-binding protein (TBP) (38). Reactions were carried out in a Bio-Rad iCycler as described (38) with the following modifications.…”

Section: Methodsmentioning

confidence: 99%

“…PCR reactions (25μl) contained 1 or 2μl cDNA template (female and male, respectively), 12.5μl 2xSYBR Green I Master Mix (Bio-Rad Laboratories, Inc., Hercules, CA), and 250nM forward and reverse primers for mCRH-BP or TATA-binding protein (TBP) (38). Reactions were carried out in a Bio-Rad iCycler as described (38) with the following modifications. The cycling conditions included 3 minutes at 95°C, 34 cycles of 95°C for 20 seconds, 62°C for 20 seconds and 72°C for 20 seconds, followed by melt-curve analysis.…”

Section: Methodsmentioning

confidence: 99%

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Pituitary CRH-binding protein and stress in female mice

Stinnett

Westphal

Seasholtz

2015

Physiology & Behavior

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The CRH-binding protein (CRH-BP) binds CRH with very high affinity and inhibits CRH-mediated ACTH release from anterior pituitary cells in vitro, suggesting that the CRH-BP functions as a negative regulator of CRH activity. Our previous studies have demonstrated sexually dimorphic expression of CRH-BP in the murine pituitary. Basal CRH-BP expression is higher in the female pituitary, where CRH-BP mRNA is detected in multiple anterior pituitary cell types. In this study, we examined stress-induced changes in CRH-BP mRNA and protein expression in mouse pituitary and assessed the in vivo role of CRH-BP in modulating the stress response. Pituitary CRH-BP mRNA was greater than 200-fold more abundant in females than males, and restraint stress increased pituitary CRH-BP mRNA by 11.8-fold in females and 3.2-fold in males as assessed by qRT-PCR. In females, restraint stress increased CRH-BP mRNA levels not only in POMC-expressing cells, but also in PRL-expressing cells. The increase in female pituitary CRH-BP mRNA following stress resulted in significant increases in CRH-BP protein 4–6 h after a 30-minute restraint stress as detected by [125I]-CRH:CRH-BP cross-linking analyses. Based on this temporal profile, the physiological role of CRH-BP was assessed using a stressor of longer duration. In lipopolysaccharide (LPS) stress studies, female CRH-BP-deficient mice showed elevated levels of stress-induced corticosterone release as compared to wild-type littermates. These studies demonstrate a role for the pituitary CRH-BP in attenuating the HPA response to stress in female mice.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Pituitary CRH-binding protein and stress in female mice

Stinnett

Westphal

Seasholtz

2015

Physiology & Behavior

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“…The upstream 900bp of the 5' flanking DNA is highly conserved across human, rat, and mouse. This region contains numerous consensus transcription factor-binding sites that are essential for the regulation of CRH-BP promoter activity (51,88,95,96). van de Stolpe and colleagues determined that the three ERE half sites in the human CRH-BP promoter specifically and functionally bound estrogen receptor (ER) alpha and ER beta in vitro (96).…”

Section: Regulation By Reproductive Hormonesmentioning

confidence: 99%

CRH-BP: the regulation and function of a phylogenetically conserved binding protein

2006

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Corticotropin Releasing Hormone-Binding Protein (CRH-BP), a 37 kDa secreted glycoprotein, binds both CRH and urocortin with high affinity and is structurally unrelated to the CRH receptors. CRH-BP orthologues have been identified in multiple invertebrate and vertebrate species. It is strongly conserved throughout evolution, suggesting the maintenance of a structural conformation necessary for biological activity. CRH-BP is an important modulator of CRH activity; it inhibits CRH-induced ACTH secretion from pituitary corticotropes and may exert similar actions at central sites of CRH release. While the function of CRH-BP is thought to be primarily inhibitory, recent studies indicate that novel functional roles may exist in both the brain and pituitary. Regulation of CRH-BP expression by stress and metabolic factors are consistent with in vivo models of altered CRH-BP expression. Positive regulation of pituitary CRH-BP by reproductive hormones suggests that additional interactions between the stress and reproductive axes may exist. While recent research has focused on the evolutionary conservation, expanded sites of expression, regulation and in vivo function of CRH-BP, a more complete understanding of the central and peripheral functions of CRH-BP and its mechanisms of action will help elucidate its potential role in the etiology or treatment of disorders of CRH dysregulation.

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“…The peptide corticotropin releasing hormone (CRH) has been described to suppress gonadal functions in situations of prolonged stress (Almeida et al, 1993;Dudas and Merchenthaler, 2006;Mitchell et al, 2005). The expression of CRH-binding protein however, is positively regulated by LHRH, highlighting the importance of the pituitary gonadotrope as a potential interface between stress and reproductive axes (Westphal and Seasholtz, 2005). We suggest that the neuropeptide GAL may serve as an integrating element, playing a pivotal role in modulating stress-related neural pathways.…”

Section: Discussionmentioning

confidence: 91%

Polymorphisms in the galanin gene are associated with symptom-severity in female patients suffering from panic disorder

et al. 2007

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Background: Galanin (GAL) is a neuropeptide, which is expressed primarily in limbic nuclei in the brain and mediates miscellaneous physiological processes and behaviors. In animal studies, both the application of GAL and antagonism of its receptors have been shown to affect anxiety-like and depression-related behavior. In humans, intravenous administration of the neuropeptide galanin has been reported to have fast antidepressant efficacy. Furthermore, GAL is involved in hypothalamichypophysiotropic signalling and cosecreted with luteinizing hormone-releasing hormone (LHRH), possibly acting as a mediator of estrogen action. Methods: In this study six single nucleotide polymorphisms (SNPs) within the gene coding for GAL were analyzed for possible associations with diagnosis and severity of symptoms in 121 male and female patients suffering from panic disorder (PD). Results: Our results suggest an association between genetic variations in the GAL-gene and severity of PD-symptoms in female patients. The most pronounced effects could be observed for two haplotypes containing the closely linked, non-protein-coding SNPs rs948854 and rs4432027. Both polymorphisms are located within CpG-dinucleotides in the promoter region of GAL and thus might be involved in epigenetic regulation of the GAL-gene. Limitations: A relatively small patient sample was analyzed in this study, the herein presented results need to be validated in independent studies. Conclusions: The results of this study underline the potential of further genetic research concerning GAL and a possible role of this neuropeptide in the pathogenesis of female PD. In this regard, GAL and its receptors appear to be a promising target for pharmacological therapy of anxiety and affective disorders.

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Gonadotropin-Releasing Hormone (GnRH) Positively Regulates Corticotropin-Releasing Hormone-Binding Protein Expression via Multiple Intracellular Signaling Pathways and a Multipartite GnRH Response Element in αT3-1 Cells

Cited by 13 publications

References 58 publications

Pituitary CRH-binding protein and stress in female mice

Pituitary CRH-binding protein and stress in female mice

CRH-BP: the regulation and function of a phylogenetically conserved binding protein

Polymorphisms in the galanin gene are associated with symptom-severity in female patients suffering from panic disorder

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