scholarly journals Acute restraint stress triggers progesterone withdrawal and endometrial breakdown and shedding through corticosterone stimulation in mouse menstrual-like model

Reproduction ◽  
2019 ◽  
pp. 149-161 ◽  
Author(s):  
Shu-Fang Wang ◽  
Xi-Hua Chen ◽  
Bin He ◽  
De-Dong Yin ◽  
Hai-Jun Gao ◽  
...  

Stress impacts the reproductive axis at the level of the hypothalamus and the pituitary gland, which exert an effect on the ovary. Menstruation is regulated by the hypothalamic–pituitary–ovary (HPO) axis. However, the role of stress in menstruation remains unclear. The objective of this study was to explore the role of stress in endometrial breakdown and shedding, using the pseudopregnant mouse menstrual-like model. Female mice were mated with vasectomized males and labeled day 0.5, upon observation of a vaginal seminal plug. On day 3.5, decidualization was induced in pseudopregnant mice using arachis oil. On day 5.5, pseudopregnant mice with artificial decidualization were placed in restraint tubes for 3 h. The findings indicated that acute restraint stress resulted in the disintegration of the endometrium. While corticosterone concentration in the serum increased significantly due to restraint stress, follicle-stimulating hormone (FSH), luteinizing hormone (LH) and progesterone (P4) levels in the serum decreased significantly. An endometrial histology examination indicated that progesterone implants may rescue P4 decline caused by acute stress and block endometrium breakdown and shedding. In addition, mice were treated with metyrapone, an inhibitor of corticosterone synthesis, 1 h prior to being subjected to restraint stress. Interestingly, metyrapone not only inhibited stress-induced endometrium breakdown and shedding, but also prevented stress-induced reduction of P4, LH and FSH. Furthermore, real-time PCR and western blot showed that mRNA and protein expression of CYP11A1 (cytochrome P450, family 11, subfamily A, polypeptide 1) and steroidogenic acute regulatory protein (StAR), the two rate-limiting enzymes for progesterone synthesis in the ovary, decreased following acute stress. But metyrapone prevented the reduction of StAR expression induced by restraint stress. Overall, this study revealed that acute stress results in an increase in corticosterone, which may inhibit LH and FSH release in the serum and CYP11A1 and StAR expression in the ovary, which finally leads to the breakdown and shedding of the endometrium. These experimental findings, based on the mouse model, may enable further understanding of the effects of stress on menstruation regulation and determine the potential factors affecting stress-associated menstrual disorders.

2017 ◽  
Vol 175 ◽  
pp. 16-21 ◽  
Author(s):  
Josiane O. Duarte ◽  
Karina S. Gomes ◽  
Ricardo L. Nunes-de-Souza ◽  
Carlos C. Crestani

Endocrinology ◽  
2012 ◽  
Vol 153 (10) ◽  
pp. 4838-4848 ◽  
Author(s):  
Guillermo A. Ariza Traslaviña ◽  
Celso Rodrigues Franci

Abstract CRH has been implicated as a mediator of stress-induced effects on the hypothalamus-pituitary-gonad axis, acting via CRH receptors in various brain regions. We investigated whether the effects of restraint stress on the secretion of gonadotropins on the morning of proestrus are mediated by the CRH-R1 or CRH-R2 receptors in the oval subdivision of the anterolateral BST, the central amygdala, the locus coeruleus (LC), or the A1 and A2 neuron groups in the medulla. At proestrus morning, rats were injected with antalarmin (a CRH-R1 antagonist), asstressin2-B (a CRH-R2 antagonist) or vehicles. Thirty minutes after the injection, the animals were placed into restraints for 30 min, and blood was sampled for 2 h. At the end of the experiment, the brains were removed for immunofluorescence analyses. Restraint stress increased the levels of FSH and LH. Antalarmin blocked the stress-induced increases in FSH and LH secretion, but astressin2-B only blocked the increase in FSH secretion. LC showed intense stress-induced neuronal activity. FOS/tyrosine-hydroxylase coexpression in LC was reduced by antalarmin, but not astressin2-B. The CRH-R1 receptor, more than CRH-R2 receptor, appears to be essential for the stimulation of the hypothalamus-pituitary-gonad axis by acute stress; this response is likely mediated in part by noradrenergic neurons in the LC. We postulate that the stress-induced facilitation of reproductive function is mediated, at least in part, by CRH action through CRH-R1 on noradrenaline neurons residing in the LC that trigger GnRH discharge and gonadotropin secretion.


2018 ◽  
Vol 239 (3) ◽  
pp. 339-350 ◽  
Author(s):  
Jennifer A Yang ◽  
Jessica K Hughes ◽  
Ruby A Parra ◽  
Katrina M Volk ◽  
Alexander S Kauffman

Restraint stress is a psychosocial stressor that suppresses reproductive status, including LH pulsatile secretion, but the neuroendocrine mechanisms underlying this inhibition remains unclear. Reproductive neural populations upstream of gonadotropin-releasing hormone (GnRH) neurons, such as kisspeptin, neurokinin B and RFRP-3 (GnIH) neurons, are possible targets for psychosocial stress to inhibit LH pulses, but this has not been well examined, especially in mice in which prior technical limitations prevented assessment of in vivo LH pulse secretion dynamics. Here, we examined whether one-time acute restraint stress alters in vivo LH pulsatility and reproductive neural populations in male mice, and what the time-course is for such alterations. We found that endogenous LH pulses in castrated male mice are robustly and rapidly suppressed by one-time, acute restraint stress, with suppression observed as quickly as 12–18 min. This rapid LH suppression parallels with increased in vivo corticosterone levels within 15 min of restraint stress. Although Kiss1, Tac2 and Rfrp gene expression in the hypothalamus did not significantly change after 90 or 180 min restraint stress, arcuate Kiss1 neural activation was significantly decreased after 180 min. Interestingly, hypothalamic Rfrp neuronal activation was strongly increased at early times after restraint stress initiation, but was attenuated to levels lower than controls by 180 min of restraint stress. Thus, the male neuroendocrine reproductive axis is quite sensitive to short-term stress exposure, with significantly decreased pulsatile LH secretion and increased hypothalamic Rfrp neuronal activation occurring rapidly, within minutes, and decreased Kiss1 neuronal activation also occurring after longer stress durations.


2021 ◽  
Vol 14 ◽  
Author(s):  
Waldo Lucas Luz ◽  
Mateus Santos-Silva ◽  
Patrick Bruno Cardoso ◽  
Nadyme Assad ◽  
Edinaldo Rogério da Silva Moraes ◽  
...  

Anxiety disorder is a well-recognized condition observed in subjects submitted to acute stress. Although the brain mechanisms underlying this disorder remain unclear, the available evidence indicates that oxidative stress and GABAergic dysfunction mediate the generation of stress-induced anxiety. Cannabinoids are known to be efficient modulators of behavior, given that the activation of the cannabinoid receptors type-1 (CB1 receptors) induces anxiolytic-like effects in animal models. In the present study, we aimed to describe the effects of the stimulation of the CB1 receptors on anxiety-like behavior, oxidative stress, and the GABA content of the brains of zebrafish submitted to acute restraint stress (ARS). The animals submitted to the ARS protocol presented evident anxiety-like behavior with increased lipid peroxidation in the brain tissue. The evaluation of the levels of GABA in the zebrafish telencephalon presented decreased levels of GABA in the ARS group in comparison with the control. Treatment with ACEA, a specific CB1 receptor agonist, prevented ARS-induced anxiety-like behavior and oxidative stress in the zebrafish brain. ACEA treatment also prevented a decrease in GABA in the telencephalon of the animals submitted to the ARS protocol. Overall, these preclinical data strongly suggest that the CB1 receptors represent a potential target for the development of the treatment of anxiety disorders elicited by acute stress.


Stress ◽  
2009 ◽  
Vol 12 (3) ◽  
pp. 268-278 ◽  
Author(s):  
C. C. Crestani ◽  
F. H. F. Alves ◽  
R. F. Tavares ◽  
F. M. A. Corrêa

Author(s):  
Sankar V ◽  
Ramanathan M ◽  
Venkatesh G

 Objective: Tuberoinfundibular peptide of 39 (TIP39) is a potent agonist to the parathyroid hormone 2 receptor (PTH2R) abundantly expressed in brain. The current study focused to evaluate the role of TIP39 in acute restraint stress (ARS)-induced depression model.Methods: Rats were exposed to ARS for 2 h to establish the depression and then subjected to open field and forced swim test (OFT and FST). TIP39 (1 and 10 nmol/rat) and HYWH (1 nmol/rat) are a PTH2R antagonist which was infused through intracerebroventricular route. Diazepam (2 mg/kg, i.p) was utilized as reference standard.Results: The results depict ARS significantly diminished the TIP39 expression in cerebral regions and causes depression-like behavior. TIP39 significantly decreased the immobility period in FST. In the OFT, TIP39 significantly increased the ambulatory activity and did not alter the rearing and grooming activity in comparison to ARS group. After TIP39 treatment, plasma noradrenaline levels were significantly increased, whereas the serotonin levels were unaltered. The corticosterone levels also decreased significantly. In rat brain tissues, TIP39 significantly reversed the abnormalities in glutamate and gamma-aminobutyric acid (GABA) level by ARS induction. In contrast, HYWH-treated rats did not show any significant variations in the neurochemical and behavioral parameters in comparison to ARS rats.Conclusion: Our reports submitted that the primary evidence depicting the stimulation of TIP39 expression could modulate the monoaminergic, GABAergic, and glutaminergic release with the support of hypothalamic-pituitary-adrenal axis that can be produced an antidepressant-like effect evident with the interactive study.


2007 ◽  
Vol 1181 ◽  
pp. 61-73 ◽  
Author(s):  
Gang Zheng ◽  
Xueping Zhang ◽  
Yaoming Chen ◽  
Yun Zhang ◽  
Wenjing Luo ◽  
...  

Endocrinology ◽  
2012 ◽  
Vol 153 (7) ◽  
pp. 3337-3344 ◽  
Author(s):  
J. Liu ◽  
P. H. Bisschop ◽  
L. Eggels ◽  
E. Foppen ◽  
E. Fliers ◽  
...  

Estrogen plays an important role in the regulation of the hypothalamus-pituitary-adrenal (HPA)-axis, but the neuroendocrine pathways and the role of estrogen receptor (ER) subtypes involved in specific aspects of this interaction remain unknown. In a first set of experiments, we administered estradiol (E2) intravenously, intracerebroventricularly, and by intrahypothalamic microdialysis to ovariectomized rats to measure plasma corticosterone (CORT) concentrations from carotid artery blood. Systemic infusion of E2 did not increase plasma CORT, but intracerebroventricular E2 induced a 3-fold CORT increase (P = 0.012). Local E2 infusions in the hypothalamic paraventricular nucleus (PVN) significantly increased plasma CORT (P < 0.001). A similar CORT increase was seen after PVN infusion of the ERα agonist propylpyrazoletriol, whereas the ERβ agonist diarylpropiolnitrile had no effect. In a second set of experiments, we investigated whether E2 modulates the HPA-axis response to acute stress by administering E2 agonists or its antagonist ICI 182,780 into the PVN during restraint stress exposure. After 30 min of stress exposure, plasma CORT had increased 5.0-fold (P < 0.001). E2 and propylpyrazoletriol administration in the PVN enhanced the stress-induced plasma CORT increase (8-fold vs. baseline), whereas ICI 182,780 and diarylpropiolnitrile reduced it, as compared with both E2 and vehicle administration in the PVN. In conclusion, central E2 modulates HPA-axis activity both in the basal state and during restraint stress. In the basal condition, the stimulation is mediated by ERα-sensitive neurons, whereas during stress, it is mediated by both ERα and ERβ.


Author(s):  
Gabriele Ghisleni ◽  
Katiucia M. Capiotti ◽  
Rosane S. Da Silva ◽  
Jean P. Oses ◽  
Ângelo L. Piato ◽  
...  

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