scholarly journals Dynamic hormone control of stress and fertility

2020 ◽  
Author(s):  
Eder Zavala ◽  
Margaritis Voliotis ◽  
Tanja Zerenner ◽  
Joël Tabak ◽  
Jamie J Walker ◽  
...  
Keyword(s):  
Stress Response ◽  
Reproductive Cycle ◽  
Network Architecture ◽  
Hormone Replacement ◽  
Coupled Systems ◽  
Dynamic Responses ◽  
Physiological Data ◽  
Reproductive Axis ◽  
Elastic Responses ◽  
Neuroendocrine Axis

ABSTRACTNeuroendocrine axes display a remarkable diversity of dynamic signalling processes relaying information between the brain, endocrine glands, and peripheral target tissues. These dynamic processes include oscillations, elastic responses to perturbations, and plastic long term changes observed from the cellular to the systems level. While small transient dynamic changes can be considered physiological, larger and longer disruptions are common in pathological scenarios involving more than one neuroendocrine axes, suggesting that a robust control of hormone dynamics would require the coordination of multiple neuroendocrine clocks. The idea of apparently different axes being in fact exquisitely intertwined through neuroendocrine signals can be investigated in the regulation of stress and fertility. The stress response and the reproductive cycle are controlled by the Hypothalamic-Pituitary-Adrenal (HPA) axis and the Hypothalamic-Pituitary-Gonadal (HPG) axis, respectively. Despite the evidence surrounding the effects of stress on fertility, as well as of the reproductive cycle on stress hormone dynamics, there is a limited understanding on how perturbations in one neuroendocrine axis propagate to the other. We hypothesize that the links between stress and fertility can be better understood by considering the HPA and HPG axes as coupled systems. In this manuscript, we investigate neuroendocrine rhythms associated to the stress response and reproduction by mathematically modelling the HPA and HPG axes as a network of interlocked oscillators. We postulate a network architecture based on physiological data and use the model to predict responses to stress perturbations under different hormonal contexts: normal physiological, gonadectomy, hormone replacement with estradiol or corticosterone (CORT), and high excess CORT (hiCORT) similar to hypercortisolism in humans. We validate our model predictions against experiments in rodents, and show how the dynamic responses of these endocrine axes are consistent with our postulated network architecture. Importantly, our model also predicts the conditions that ensure robustness of fertility to stress perturbations, and how chronodisruptions in glucocorticoid hormones can affect the reproductive axis’ ability to withstand stress. This insight is key to understand how chronodisruption leads to disease, and to design interventions to restore normal rhythmicity and health.

scholarly journals Dynamic Responses to Acute Heat Stress between 34 °C and 38.5 °C, and Characteristics of Heat Stress Response in Mice

2003 ◽  
Vol 26 (5) ◽  
pp. 701-708 ◽  
Author(s):  
Naoki Harikai ◽  
Kanji Tomogane ◽  
Mitsue Miyamoto ◽  
Keiko Shimada ◽  
Satoshi Onodera ◽  
...  
Keyword(s):  
Heat Stress ◽  
Stress Response ◽  
Dynamic Responses ◽  
Heat Stress Response ◽  
Acute Heat Stress

A Virtual Reality Version of the Trier Social Stress Test: A Pilot Study

2011 ◽  
Vol 20 (4) ◽  
pp. 325-336 ◽  
Author(s):  
Mattias Wallergård ◽  
Peter Jönsson ◽  
Gerd Johansson ◽  
Björn Karlson
Keyword(s):  
Virtual Reality ◽  
Stress Response ◽  
Pilot Study ◽  
Social Stress ◽  
Stress Test ◽  
Structured Interview ◽  
Trier Social Stress Test ◽  
Physiological Data ◽  
Virtual Humans ◽  
Arithmetic Task

One of the most common methods of inducing stress in the laboratory in order to examine the stress response in healthy and clinical populations is the Trier Social Stress Test (TSST). Briefly, the participant is asked to deliver a speech and to perform an arithmetic task in front of an evaluating committee. The committee, consisting of three trained actors, does not respond emotionally during the test, which makes the situation very stressful for the participant. One disadvantage of the TSST is that it can be difficult to hold the experimental conditions constant. In particular, it may be difficult for actors to hold their acting constant across all sessions. Furthermore, there are several practical problems and costs associated with hiring professional actors. A computerized version of the TSST using virtual humans could be a way to avoid these problems provided that it is able to induce a stress response similar to the one of the original TSST. The purpose of the present pilot study was therefore to investigate the stress response to a virtual reality (VR) version of the TSST visualized using an immersive VR system (VR-TSST). Seven healthy males with an average age of 24 years (range: 23–26 years) performed the VR-TSST. This included delivering a speech and performing an arithmetic task in front of an evaluating committee consisting of three virtual humans. The VR equipment was a CAVE equipped with stereoscopy and head tracking. ECG and respiration were recorded as well as the participant's behavior and comments. Afterward, a semi-structured interview was carried out. In general, the subjective and physiological data from the experiment indicated that the VR version of the TSST induced a stress response in the seven participants. In particular, the peak increase in heart rate was close to rates observed in studies using the traditional TSST with real actors. These results suggest that virtual humans visualized with an immersive VR system can be used to induce stress under laboratory conditions.

scholarly journals Dynamic responses of the adrenal steroidogenic regulatory network

2017 ◽  
Vol 114 (31) ◽  
pp. E6466-E6474 ◽  
Author(s):  
Francesca Spiga ◽  
Eder Zavala ◽  
Jamie J. Walker ◽  
Zidong Zhao ◽  
John R. Terry ◽  
...  
Keyword(s):  
Regulatory Network ◽  
Network Architecture ◽  
Dynamic Network ◽  
Dynamic Responses ◽  
Key Factors ◽  
Inflammatory Stress ◽  
Hormone Synthesis ◽  
Regulatory Processes ◽  
Immune Pathway ◽  
Pituitary Adrenal Axis

The hypothalamic–pituitary–adrenal axis is a dynamic system regulating glucocorticoid hormone synthesis in the adrenal glands. Many key factors within the adrenal steroidogenic pathway have been identified and studied, but little is known about how these factors function collectively as a dynamic network of interacting components. To investigate this, we developed a mathematical model of the adrenal steroidogenic regulatory network that accounts for key regulatory processes occurring at different timescales. We used our model to predict the time evolution of steroidogenesis in response to physiological adrenocorticotropic hormone (ACTH) perturbations, ranging from basal pulses to larger stress-like stimulations (e.g., inflammatory stress). Testing these predictions experimentally in the rat, our results show that the steroidogenic regulatory network architecture is sufficient to respond to both small and large ACTH perturbations, but coupling this regulatory network with the immune pathway is necessary to explain the dissociated dynamics between ACTH and glucocorticoids observed under conditions of inflammatory stress.

scholarly journals Pseudomonas fluorescens Induces Strain-Dependent and Strain-Independent Host Plant Responses in Defense Networks, Primary Metabolism, Photosynthesis, and Fitness

2012 ◽  
Vol 25 (6) ◽  
pp. 765-778 ◽  
Author(s):  
David J. Weston ◽  
Dale A. Pelletier ◽  
Jennifer L. Morrell-Falvey ◽  
Timothy J. Tschaplinski ◽  
Sara S. Jawdy ◽  
...  
Keyword(s):  
Pseudomonas Fluorescens ◽  
Host Plant ◽  
Network Architecture ◽  
Plant Performance ◽  
Molecular Networks ◽  
Physiological Data ◽  
Carbon Gain ◽  
Plant Responses ◽  
Primary Metabolism ◽  
Pathway Regulation

Colonization of plants by nonpathogenic Pseudomonas fluorescens strains can confer enhanced defense capacity against a broad spectrum of pathogens. Few studies, however, have linked defense pathway regulation to primary metabolism and physiology. In this study, physiological data, metabolites, and transcript profiles are integrated to elucidate how molecular networks initiated at the root–microbe interface influence shoot metabolism and whole-plant performance. Experiments with Arabidopsis thaliana were performed using the newly identified P. fluorescens GM30 or P. fluorescens Pf-5 strains. Co-expression networks indicated that Pf-5 and GM30 induced a subnetwork specific to roots enriched for genes participating in RNA regulation, protein degradation, and hormonal metabolism. In contrast, only GM30 induced a subnetwork enriched for calcium signaling, sugar and nutrient signaling, and auxin metabolism, suggesting strain dependence in network architecture. In addition, one subnetwork present in shoots was enriched for genes in secondary metabolism, photosynthetic light reactions, and hormone metabolism. Metabolite analysis indicated that this network initiated changes in carbohydrate and amino acid metabolism. Consistent with this, we observed strain-specific responses in tryptophan and phenylalanine abundance. Both strains reduced host plant carbon gain and fitness, yet provided a clear fitness benefit when plants were challenged with the pathogen P. syringae DC3000.

scholarly journals Mapping the cellular response to electron transport chain inhibitors reveals selective signaling networks triggered by mitochondrial perturbation

2021 ◽  
Author(s):  
Wanda van der Stel ◽  
Huan Yang ◽  
Nanette G. Vrijenhoek ◽  
Johannes P. Schimming ◽  
Giulia Callegaro ◽  
...  
Keyword(s):  
Stress Response ◽  
Electron Transport ◽  
Cell Viability ◽  
Electron Transport Chain ◽  
Cellular Response ◽  
Cellular Responses ◽  
Dynamic Responses ◽  
Gene Set ◽  
Transport Chain ◽  
The Impact

AbstractMitochondrial perturbation is a key event in chemical-induced organ toxicities that is incompletely understood. Here, we studied how electron transport chain (ETC) complex I, II, or III (CI, CII and CIII) inhibitors affect mitochondrial functionality, stress response activation, and cell viability using a combination of high-content imaging and TempO-Seq in HepG2 hepatocyte cells. CI and CIII inhibitors perturbed mitochondrial membrane potential (MMP) and mitochondrial and cellular ATP levels in a concentration- and time-dependent fashion and, under conditions preventing a switch to glycolysis attenuated cell viability, whereas CII inhibitors had no effect. TempO-Seq analysis of changes in mRNA expression pointed to a shared cellular response to CI and CIII inhibition. First, to define specific ETC inhibition responses, a gene set responsive toward ETC inhibition (and not to genotoxic, oxidative, or endoplasmic reticulum stress) was identified using targeted TempO-Seq in HepG2. Silencing of one of these genes, NOS3, exacerbated the impact of CI and CIII inhibitors on cell viability, indicating its functional implication in cellular responses to mitochondrial stress. Then by monitoring dynamic responses to ETC inhibition using a HepG2 GFP reporter panel for different classes of stress response pathways and applying pathway and gene network analysis to TempO-Seq data, we looked for downstream cellular events of ETC inhibition and identified the amino acid response (AAR) as being triggered in HepG2 by ETC inhibition. Through in silico approaches we provide evidence indicating that a similar AAR is associated with exposure to mitochondrial toxicants in primary human hepatocytes. Altogether, we (i) unravel quantitative, time- and concentration-resolved cellular responses to mitochondrial perturbation, (ii) identify a gene set associated with adaptation to exposure to active ETC inhibitors, and (iii) show that ER stress and an AAR accompany ETC inhibition in HepG2 and primary hepatocytes.

scholarly journals Effect of thymectomy on the female reproductive cycle in neonatal guinea pigs

2020 ◽  
Vol 47 (1) ◽  
pp. 12-19
Author(s):  
P. Murali ◽  
J. Radhika ◽  
D. Alwin
Keyword(s):  
Reproductive Cycle ◽  
Guinea Pigs ◽  
Neonatal Period ◽  
Reproductive Function ◽  
Normal Female ◽  
Vaginal Opening ◽  
Estrus Cycle ◽  
Reproductive Axis ◽  
17Β Estradiol ◽  
Estradiol Levels

Objective: The appropriate function of the hypothalamic-pituitary-gonadal axis is essential for maintaining proper reproductive function. In female mammals, the hypothalamic-pituitary-gonadal axis regulates reproductive changes that take place in the estrus cycle and are necessary for successful reproduction. This study was conducted to investigate the effect of thymectomy on the estrus cycle in neonatally thymectomized guinea pigs.Methods: In this study, 12 female guinea pigs, six thymectomized and six sham-operated, were studied. The effects of neonatal thymectomy at 5–7 days of age on parameters of the reproductive axis were examined in female guinea pigs. Gonadotropin and 17β-estradiol levels were assessed at regular intervals (days 0, 3, 6, 9, 12, and 15) of the estrus cycle, and the time of vaginal opening in the thymectomized and shamoperated guinea pigs was determined.Results: Significant reductions in gonadotropins and 17β-estradiol levels during estrus cycle were found in neonatally thymectomized female guinea pigs compared to sham-operated guinea pigs.Conclusion: The results of this study underscore the importance of the thymus in the neonatal period for normal female reproductive function.

scholarly journals Dynamic responses of electrically coupled systems.

1986 ◽  
Vol 87 (4) ◽  
pp. 513-531
Author(s):  
N G Publicover
Keyword(s):  
Phase Shift ◽  
Synaptic Transmission ◽  
Coupled System ◽  
Coupled Systems ◽  
Dynamic Responses ◽  
Principle Of Superposition ◽  
Buccal Ganglion ◽  
Low Frequencies ◽  
High Frequencies ◽  
Frequency Responses

An identified pair of electrically coupled neurons in the buccal ganglion of the freshwater snail Helisoma trivolvis is an experimentally accessible model of electrical synaptic transmission. In this investigation, electrical synaptic transmission is characterized using sinusoidal frequency (Bode) responses computed by Laplace transforms and responses to brief stimuli. The frequency response of the injected neuron shows a 20-dB/decade attenuation and a phase shift from 0 degree at low frequencies to -90 degrees at high frequencies. The response of a coupled cell shows a 40-dB/decade attenuation and a phase shift from 0 degrees at low frequencies to -180 degrees at high frequencies. A simple mathematical model of electrical synaptic transmission is described that displays each of these crucial features of the measured frequency responses. Methods are described to estimate the frequency responses of coupled systems based on presynaptic measurements. The responses of the coupled system to brief pulses of current were computed using the principle of superposition. The electrical properties of coupled systems impose a minimum delay in reaching a peak in all postsynaptic responses. The delays in the postsynaptic responses to brief stimuli are related to the electrical and anatomical parameters of coupled networks.

Redistribution of Synaptic Efficacy Supports Stable Pattern Learning in Neural Networks

2002 ◽  
Vol 14 (4) ◽  
pp. 873-888 ◽  
Author(s):  
Gail A. Carpenter ◽  
Boriana L. Milenova
Keyword(s):  
Frequency Dependence ◽  
Network Architecture ◽  
Single Pulse ◽  
Long Term Potentiation ◽  
Physiological Data ◽  
Long Term Memory ◽  
Synaptic Efficacy ◽  
Stable Pattern ◽  
Dependent Signal

Markram and Tsodyks, by showing that the elevated synaptic efficacy observed with single-pulse long-term potentiation (LTP) measurements disappears with higher-frequency test pulses, have critically challenged the conventional assumption that LTP reflects a general gain increase. This observed change in frequency dependence during synaptic potentiation is called redistribution of synaptic efficacy (RSE). RSE is here seen as the local realization of a global design principle in a neural network for pattern coding. The underlying computational model posits an adaptive threshold rather than a multiplicative weight as the elementary unit of long-term memory. A distributed instar learning law allows thresholds to increase only monotonically, but adaptation has a bidirectional effect on the model postsynaptic potential. At each synapse, threshold increases implement pattern selectivity via a frequency-dependent signal component, while a complementary frequency-independent component nonspecifically strengthens the path. This synaptic balance produces changes in frequency dependence that are robustly similar to those observed by Markram and Tsodyks. The network design therefore suggests a functional purpose for RSE, which, by helping to bound total memory change, supports a distributed coding scheme that is stable with fast as well as slow learning. Multiplicative weights have served as a cornerstone for models of physiological data and neural systems for decades. Although the model discussed here does not implement detailed physiology of synaptic transmission, its new learning laws operate in a network architecture that suggests how recently discovered synaptic computations such as RSE may help produce new network capabilities such as learning that is fast, stable, and distributed.

scholarly journals Neurokinin 3 Receptor Antagonism: A Novel Treatment for Menopausal Hot Flushes

2018 ◽  
Vol 109 (3) ◽  
pp. 242-248 ◽  
Author(s):  
Manish Modi ◽  
Waljit S. Dhillo
Keyword(s):  
Hormone Replacement Therapy ◽  
Replacement Therapy ◽  
Postmenopausal Women ◽  
Hormone Replacement ◽  
Treatment Options ◽  
Hot Flushes ◽  
Reproductive Axis ◽  
Hot Flush ◽  
Night Sweats ◽  
Neurokinin 3 Receptor

Menopause is associated with significant symptomatic burden, with approximately two-thirds of postmenopausal women suffering from vasomotor symptoms, hot flushes, and night sweats. The mainstay of treatment for hot flushes continues to be hormone replacement therapy. However, as hormone replacement therapy is contraindicated in some cases, alternative, efficacious treatment options are also required. Hot flushes are thought to arise as a result of significant changes in the neuroendocrine circuitry underpinning the reproductive axis during menopause. This includes reduced circulating ovarian oestrogens, hypersecretion of gonadotropins, and increased expression of kisspeptin and neurokinin B (NKB) within the infundibular nucleus of the hypothalamus. In recent years, NKB, predominantly acting via the neurokinin 3 receptor (NK3R), has emerged as an important player in the development of menopausal hot flushes. Antagonism of NK3R has garnered much interest as a novel therapeutic target to help ameliorate hot flush symptoms. Improvements in hot flush frequency, severity, and quality of life have been demonstrated in a number of clinical trials using novel NK3R antagonists in postmenopausal women. Within this review, we will explore the growing body of evidence supporting antagonism of NK3R as a potentially promising treatment for menopausal hot flushes.

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