Postpartum Fatigue and Inhibited Lactation

2021 ◽  
pp. 109980042110500
Author(s):  
Feng Zhang ◽  
Qin Xue ◽  
Ting Bai ◽  
Fan Wu ◽  
Shuhan Yan
Keyword(s):  
Mammary Gland ◽  
Signaling Pathway ◽  
Light And Electron Microscopy ◽  
Chronic Fatigue ◽  
Janus Kinase ◽  
Inhibition Mechanism ◽  
Signal Transducers ◽  
Downstream Signaling ◽  
Transmission Electron ◽  
Postpartum Fatigue

Background: Postpartum fatigue is a common disorder worldwide and affects both physical and mental functioning. In breastfeeding women, Prolactin (PRL) is not only involved in immunoregulation, but also responsible for lactation. Prolactin levels in women with chronic fatigue are higher than normal, but a chronic fatigue state inhibits postpartum lactation in humans. Objectives: This paper explored the inhibition mechanism of lactation by postpartum fatigue in rats. Methods: Postpartum fatigue models were built by forcing mother rats to stand in water and divided into 3-hour, 9-hour and 15-hour per day fatigue groups according to the underwater time. Mother rats and their offspring were reunited in a dry cage for 90 minutes every 3 hours for feeding. The expression of PRL, PRL receptor (PRLR), Janus Kinase 2 (JAK 2), and Signal transducers and activators of transcription 5 (STAT5) mRNA were analyzed and the microstructure of mammary gland were observed under light and electron microscopy. Results: The expression of pituitary PRL mRNA and its downstream signaling pathway JAK2 and STAT5 mRNA were down-regulated in the severe postpartum fatigue rats. PRL mRNA responses were dose-related to duration of fatigue. The expression of PRLR mRNA increased. Postpartum fatigue led to functional degeneration of mammary gland. The breast lobules were shrunk and the number of alveoli were decreased. Few milk protein granules and fat droplets were observed in the cytoplasm under transmission electron microscope. Conclusion: Postpartum fatigue inhibits the lactation by down-regulating the expression of PRL and PRL-dependent signaling pathway in rats.

Liraglutide Exerts Potential Anti-inflammatory Effect in Type 1 Diabetes by Inhibiting IFN-γ Production via Suppressing JAK-STAT Pathway

2019 ◽  
Vol 19 (5) ◽  
pp. 656-664
Author(s):  
Yunjuan Zhao ◽  
Yunliang Xie ◽  
Wangen Li
Keyword(s):  
Type 1 Diabetes ◽  
Signaling Pathway ◽  
Interferon Γ ◽  
Janus Kinase ◽  
Janus Kinase 2 ◽  
Signal Transducers ◽  
High Glucose Condition ◽  
Glucose Condition ◽  
Signal Transducers And Activators

Background: Type 1 diabetes is a T cell-mediated autoimmune disease. Interferon γ plays a critical role in the pathogenesis of type 1 diabetes. Signal transducer and activator of transcription transduces type I interferon cytokines in T cells, leading to Th1 cell differentiation and production of interferon γ. Recent studies suggest that liraglutide reduces the plasma concentration of C-reative protein in patients with type 1 diabetes and protects β cell function in the non-obese diabetic mouse. Objective: The study aimed to explore the effect of glucagon-like peptide-1 analogue on interferon γ production and the underlying signaling pathway in vitro. Methods: Jurkat E6-1 cells were intervened with different concentrations of glucose and liraglutide during different time periods. Protein was extracted from Jurkat E6-1 cells. The target proteins (total and activated Janus kinase 2, signal transducers and activators of transcription 4 and interferon γ) were detected by Western blot. Results: Glucose stimulates interferon γ expression and activates Janus kinase 2/signal transducers and activators of transcription 4 signaling pathway in Jurkat E6-1 cells in a concentration and timedependent manner. Under high glucose condition, liraglutide inhibits interferon γ expression and Janus kinase 2/signal transducers and activators of transcription 4 signaling pathway in Jurkat E6-1 cells in a concentration and time-dependent manner. The Janus kinase responsible for liraglutide-inhibited signal transducers and activators of transcription 4 phosphorylation is Janus kinase 2, which is also required for the interferon γ induction. Finally, we demonstrated that under high glucose condition, liraglutide inhibits interferon γ expression via Janus kinase 2/signal transducers and activators of transcription 4 signaling pathway in Jurkat E6-1 cells. Conclusion: Liraglutide inhibits Jurkat E6-1 cells to produce interferon γ via the Janus kinase/signal transducers and activators of transcription signaling pathway under high glucose condition, which implies its potential in the immunoregulatory effect of type 1 diabetes.

scholarly journals Inherent Growth Hormone Resistance in the Skeletal Muscle of the Fine Flounder Is Modulated by Nutritional Status and Is Characterized by High Contents of Truncated GHR, Impairment in the JAK2/STAT5 Signaling Pathway, and Low IGF-I Expression

Endocrinology ◽  
2012 ◽  
Vol 153 (1) ◽  
pp. 283-294 ◽  
Author(s):  
Eduardo N. Fuentes ◽  
Ingibjörg Eir Einarsdottir ◽  
Juan Antonio Valdes ◽  
Marco Alvarez ◽  
Alfredo Molina ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Signaling Pathway ◽  
Growth Regulation ◽  
Slow Growth ◽  
Muscle Growth ◽  
Janus Kinase ◽  
Signal Transducers ◽  
Igf I ◽  
Plasma Gh ◽  
Gh Resistance

A detailed understanding of how the GH and IGF-I regulate muscle growth, especially in early vertebrates, is still lacking. The fine flounder is a flatfish species exhibiting remarkably slow growth, representing an intriguing model for elucidating growth regulatory mechanisms. Key components of the GH system were examined in groups of fish during periods of feeding, fasting, and refeeding. Under feeding conditions, there is an inherent systemic and local (muscle) GH resistance, characterized by higher levels of plasma GH than of IGF-I, skeletal muscle with a greater content of the truncated GH receptor (GHRt) than of full-length GHR (GHRfl), an impaired activation of the Janus kinase 2 (JAK2)-signal transducers and activators of transcription 5 (STAT5) signaling pathway, and low IGF-I expression. Fasting leads to further elevation of plasma GH levels concomitant with suppressed IGF-I levels. The ratio of GHRfl to GHRt in muscle decreases during fasting, causing an inactivation of the JAK2/STAT5 signaling pathway and suppressed IGF-I expression, further impairing growth. When fish are returned to nutritionally favorable conditions, plasma GH levels decrease, and the ratio of GHRfl to GHRt in muscle increases, triggering JAK2/STAT5 reactivation and local IGF-I expression, concomitant with increased growth. The study suggests that systemic IGF-I is supporting basal slow growth in this species, without ruling out that local IGF-I is participating in muscle growth. These results reveal for the first time a unique model of inherent GH resistance in the skeletal muscle of a nonmammalian species and contribute to novel insights of the endocrine and molecular basis of growth regulation in earlier vertebrates.

Therapeutic potential of JAK/STAT pathway modulation in mood disorders

2018 ◽  
Vol 30 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Aisha S. Shariq ◽  
Elisa Brietzke ◽  
Joshua D. Rosenblat ◽  
Zihang Pan ◽  
Carola Rong ◽  
...  
Keyword(s):  
Mood Disorders ◽  
Signaling Pathway ◽  
Depressive Disorders ◽  
Therapeutic Potential ◽  
Indirect Evidence ◽  
Janus Kinase ◽  
Low Grade ◽  
Signal Transducers ◽  
Inflammatory Conditions ◽  
Stat Signaling

Abstract Convergent evidence demonstrates that immune dysfunction (e.g. chronic low-grade inflammatory activation) plays an important role in the development and progression of mood disorders. The Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathway is a pleiotropic cellular cascade that transduces numerous signals, including signals from the release of cytokines and growth factors. The JAK/STAT signaling pathway is involved in mediating several functions of the central nervous system, including neurogenesis, synaptic plasticity, gliogenesis, and microglial activation, all of which have been implicated in the pathophysiology of mood disorders. In addition, the antidepressant actions of current treatments have been shown to be mediated by JAK/STAT-dependent mechanisms. To date, two JAK inhibitors (JAKinibs) have been approved by the U.S. Food and Drug Administration and are primarily indicated for the treatment of inflammatory conditions such as rheumatoid arthritis. Indirect evidence from studies in populations with inflammatory conditions indicates that JAKinibs significantly improve measures of mood and quality of life. There is also direct evidence from studies in populations with depressive disorders, suggesting that JAK/STAT pathways may be involved in the pathophysiology of depression and that the inhibition of specific JAK/STAT pathways (i.e. via JAKinibs) may be a promising novel treatment for depressive disorders.

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