scholarly journals Isolating the Role of Corticosterone in the Hypothalamic-Pituitary-Gonadal Transcriptomic Stress Response

2021 ◽  
Vol 12 ◽  
Author(s):  
Suzanne H. Austin ◽  
Rayna M. Harris ◽  
April M. Booth ◽  
Andrew S. Lang ◽  
Victoria S. Farrar ◽  
...  
Keyword(s):  
Stress Response ◽  
Differential Expression ◽  
Restraint Stress ◽  
Columba Livia ◽  
Transcriptomic Response ◽  
Hpg Axis ◽  
Adrenal Steroid ◽  
Negative Impacts ◽  
Prolactin Synthesis

Investigation of the negative impacts of stress on reproduction has largely centered around the effects of the adrenal steroid hormone, corticosterone (CORT), and its influence on a system of tissues vital for reproduction—the hypothalamus of the brain, the pituitary gland, and the gonads (the HPG axis). Research on the action of CORT on the HPG axis has predominated the stress and reproductive biology literature, potentially overshadowing other influential mediators. To gain a more complete understanding of how elevated CORT affects transcriptomic activity of the HPG axis, we experimentally examined its role in male and female rock doves (Columba livia). We exogenously administrated CORT to mimic circulating levels during the stress response, specifically 30 min of restraint stress, an experimental paradigm known to increase circulating CORT in vertebrates. We examined all changes in transcription within each level of the HPG axis as compared to both restraint-stressed birds and vehicle-injected controls. We also investigated the differential transcriptomic response to CORT and restraint-stress in each sex. We report causal and sex-specific effects of CORT on the HPG transcriptomic stress response. Restraint stress caused 1567 genes to uniquely differentially express while elevated circulating CORT was responsible for the differential expression of 304 genes. Only 108 genes in females and 8 in males differentially expressed in subjects that underwent restraint stress and those who were given exogenous CORT. In response to elevated CORT and restraint-stress, both sexes shared the differential expression of 5 genes, KCNJ5, CISH, PTGER3, CEBPD, and ZBTB16, all located in the pituitary. The known functions of these genes suggest potential influence of elevated CORT on immune function and prolactin synthesis. Gene expression unique to each sex indicated that elevated CORT affected more gene transcription in females than males (78 genes versus 3 genes, respectively). To our knowledge, this is the first study to isolate the role of CORT in HPG genomic transcription during a stress response. We present an extensive and openly accessible view of the role corticosterone in the HPG transcriptomic stress response. Because the HPG system is well conserved across vertebrates, these data have the potential to inspire new therapeutic strategies for reproductive dysregulation in multiple vertebrate systems, including our own.

scholarly journals Isolating the role of corticosterone in the hypothalamic-pituitary-gonadal genomic stress response

2020 ◽  
Author(s):  
Suzanne H. Austin ◽  
Rayna Harris ◽  
April M. Booth ◽  
Andrew S. Lang ◽  
Victoria S. Farrar ◽  
...  
Keyword(s):  
Stress Response ◽  
Differential Expression ◽  
Restraint Stress ◽  
Columba Livia ◽  
Hpg Axis ◽  
Adrenal Steroid ◽  
Genomic Stress ◽  
Negative Impacts ◽  
Prolactin Synthesis

ABSTRACTThe negative impacts of stress on reproduction have long been studied. A large focus of investigation has centered around the effects of the adrenal steroid hormone corticosterone (CORT) on a system of tissues vital for reproduction, the hypothalamus of the brain, the pituitary gland, and the gonads (the HPG axis). Investigations of the role of CORT on the HPG axis have predominated the stress and reproductive biology literature, potentially overshadowing other influential mediators. To gain a more complete understanding of how elevated CORT, characteristic of the stress response, affects the activity of the HPG axis, we experimentally examined its role at the level of the genome in both male and female rock doves (Columba livia). We exogenously administrated CORT to mimic circulating levels during the stress response, specifically 30 min of restraint stress, an experimental paradigm known to increase circulating corticosterone in vertebrates. We examined all changes in genomic transcription within the HPG axis as compared to both restraint-stressed birds and vehicle-injected controls, as well as between the sexes. We report causal and sex-specific effects of CORT on the HPG stress response at the level of the transcriptome. Restraint stress caused 1567 genes to uniquely differentially express while elevated circulating CORT was responsible for the differential expression of 304 genes. Only 108 genes in females and 8 in males differentially expressed in subjects who underwent restraint stress and those who were given exogenous CORT. In response to CORT elevation characteristic of the stress response, both sexes shared the differential expression of 5 genes, KCNJ5, CISH, PTGER3, CEBPD, and ZBTB16, all located in the pituitary. The known functions of these genes suggest potential influence of elevated CORT on immune function and prolactin synthesis. Gene expression unique to each sex indicated that elevated CORT affected more gene transcription in females than males (78 genes versus 3 genes, respectively). To our knowledge, this is the first study to isolate the role of CORT in HPG genomic transcription during a stress response. These results provide novel targets for new lines of further investigation and therapy development. We present an extensive and openly accessible view of the role corticosterone in the HPG genomic stress response, offering novel gene targets to inspire new lines of investigation of stress-induced reproductive dysfunction. Because the HPG system is well-conserved across vertebrates, these data have the potential to inspire new therapeutic strategies for reproductive dysregulation in multiple vertebrate systems, including our own.

scholarly journals Stress-mediated convergence of splicing landscapes in male and female Rock Doves

2019 ◽  
Author(s):  
Andrew S Lang ◽  
Suzanne H Austin ◽  
Rayna M Harris ◽  
Rebecca M Calisi ◽  
Matthew D MacManes
Keyword(s):  
Sexual Behavior ◽  
Alternative Splicing ◽  
Stress Response ◽  
Drug Targets ◽  
Columba Livia ◽  
Hpg Axis ◽  
Behavioral Complexity ◽  
Coding Regions ◽  
Males And Females ◽  
And Control

AbstractBackgroundThe process of alternative splicing provides a unique mechanism by which eukaryotes are able to produce numerous protein products from the same gene. Heightened variability in the proteome has been thought to potentiate increased behavioral complexity and response flexibility to environmental stimuli, thus contributing to more refined traits on which natural and sexual selection can act. While it has been long known that various forms of environmental stress can negatively affect sexual behavior and reproduction, we know little of how stress can affect the alternative splicing associated with these events, and less still about how splicing may differ between sexes. Using the model of the rock dove (Columba livia), our team previously uncovered sexual dimorphism in the basal and stress-responsive gene transcription of a biological system necessary for facilitating sexual behavior and reproduction, the hypothlamic-pituitary-gonadal (HPG) axis. In this study, we delve further into understanding the mechanistic underpinnings of how changes in the environment can affect reproduction by testing the alternative splicing response of the HPG axis to an external stressor in both sexes.ResultsThis study reveals dramatic baseline differences in HPG alternative splicing between males and females. However, post submitting subjects to a restraint stress paradigm, we found a significant reduction in these differences between the sexes. In both stress and control treatments, we identified a higher incidence of splicing activity in the pituitary in both sexes as compared to other tissues. Of these splicing events, the core exon event is the most abundant form of splicing and more frequently occurs in the coding regions of the gene. Overall, we observed less splicing activity in the 3’UTR end of transcripts than the 5’UTR or coding regions.ConclusionsOur results provide vital new insight into sex-specific aspects of the stress response on the HPG axis at an unprecedented proximate level. Males and females uniquely respond to stress, yet exhibit splicing patterns suggesting a convergent, optimal splicing landscape for stress response. This information has the potential to inform evolutionary theory as well as the development of highly-specific drug targets for stress-induced reproductive dysfunction.

scholarly journals Differential expression and role of p21cip/waf1 and p27kip1 in TNF-α-induced inhibition of proliferation in human glioma cells

2007 ◽  
Vol 6 (1) ◽  
pp. 42 ◽  
Author(s):  
Pabbisetty Kumar ◽  
Anjali Shiras ◽  
Gowry Das ◽  
Jayashree C Jagtap ◽  
Vandna Prasad ◽  
...  
Keyword(s):  
Differential Expression ◽  
Glioma Cells ◽  
Human Glioma ◽  
Human Glioma Cells ◽  
Inhibition Of Proliferation ◽  
Tnf Α

scholarly journals Flavonoids: Potential Candidates for the Treatment of Neurodegenerative Disorders

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 99
Author(s):  
Shweta Devi ◽  
Vijay Kumar ◽  
Sandeep Kumar Singh ◽  
Ashish Kant Dubey ◽  
Jong-Joo Kim
Keyword(s):  
Stress Response ◽  
Stress Responses ◽  
Neurodegenerative Disorders ◽  
Cell Damage ◽  
Cellular Stress ◽  
Clinical Manifestations ◽  
Cellular Stress Response ◽  
Dramatic Rise ◽  
Cellular Stress Responses

Neurodegenerative disorders, such as Parkinson’s disease (PD), Alzheimer’s disease (AD), Amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD), are the most concerning disorders due to the lack of effective therapy and dramatic rise in affected cases. Although these disorders have diverse clinical manifestations, they all share a common cellular stress response. These cellular stress responses including neuroinflammation, oxidative stress, proteotoxicity, and endoplasmic reticulum (ER)-stress, which combats with stress conditions. Environmental stress/toxicity weakened the cellular stress response which results in cell damage. Small molecules, such as flavonoids, could reduce cellular stress and have gained much attention in recent years. Evidence has shown the potential use of flavonoids in several ways, such as antioxidants, anti-inflammatory, and anti-apoptotic, yet their mechanism is still elusive. This review provides an insight into the potential role of flavonoids against cellular stress response that prevent the pathogenesis of neurodegenerative disorders.

scholarly journals Mitochondrien unter Stress: Die Rolle der Präsequenzprotease MPP

BIOspektrum ◽  
2021 ◽  
Vol 27 (4) ◽  
pp. 390-393
Author(s):  
F.-Nora Vögtle
Keyword(s):  
Stress Response ◽  
Cellular Stress ◽  
Critical Role ◽  
Mitochondrial Protein ◽  
Nuclear Genome ◽  
Cellular Stress Response ◽  
Mitochondrial Proteins ◽  
Protein Biogenesis ◽  
Cellular Integrity

AbstractThe majority of mitochondrial proteins are encoded in the nuclear genome, so that the nearly entire proteome is assembled by post-translational preprotein import from the cytosol. Proteomic imbalances are sensed and induce cellular stress response pathways to restore proteostasis. Here, the mitochondrial presequence protease MPP serves as example to illustrate the critical role of mitochondrial protein biogenesis and proteostasis on cellular integrity.

scholarly journals Overexpression of the Apple (Malus× domestica) MdERF100 in Arabidopsis Increases Resistance to Powdery Mildew

2021 ◽  
Vol 22 (11) ◽  
pp. 5713
Author(s):  
Yiping Zhang ◽  
Li Zhang ◽  
Hai Ma ◽  
Yichu Zhang ◽  
Xiuming Zhang ◽  
...  
Keyword(s):  
Stress Response ◽  
Powdery Mildew ◽  
Malus Domestica ◽  
Molecular Mechanisms ◽  
Powdery Mildew Resistance ◽  
Bimolecular Fluorescence Complementation ◽  
Bhlh Protein ◽  
Mildew Resistance ◽  
Sa Signaling

APETALA2/ETHYLENE RESPONSIVE FACTOR (AP2/ERF) transcription factors play important roles in plant development and stress response. Although AP2/ERF genes have been extensively investigated in model plants such as Arabidopsis thaliana, little is known about their role in biotic stress response in perennial fruit tree crops such as apple (Malus × domestica). Here, we investigated the role of MdERF100 in powdery mildew resistance in apple. MdERF100 localized to the nucleus but showed no transcriptional activation activity. The heterologous expression of MdERF100 in Arabidopsis not only enhanced powdery mildew resistance but also increased reactive oxygen species (ROS) accumulation and cell death. Furthermore, MdERF100-overexpressing Arabidopsis plants exhibited differential expressions of genes involved in jasmonic acid (JA) and salicylic acid (SA) signaling when infected with the powdery mildew pathogen. Additionally, yeast two-hybrid and bimolecular fluorescence complementation assays confirmed that MdERF100 physically interacts with the basic helix–loop–helix (bHLH) protein MdbHLH92. These results suggest that MdERF100 mediates powdery mildew resistance by regulating the JA and SA signaling pathways, and MdbHLH92 is involved in plant defense against powdery mildew. Overall, this study enhances our understanding of the role of MdERF genes in disease resistance, and provides novel insights into the molecular mechanisms of powdery mildew resistance in apple.

Sign in / Sign up

Export Citation Format

Share Document