RÉSUMÉ
The hypothalamic-pituitary-ovarian (HPO) axis represents a central neuroendocrine network essential for reproductive function. Despite its critical role, the intrinsic heterogeneity within the HPO axis across vertebrates and the complex intercellular interactions remain poorly defined. This study provides the first comprehensive, unbiased, cell type-specific molecular profiling of all three components of the HPO axis in adult Lohmann layers and Liangshan Yanying chickens. Within the hypothalamus, pituitary, and ovary, seven, 12, and 13 distinct cell types were identified, respectively. Results indicated that the pituitary adenylate cyclase activating polypeptide (PACAP), follicle-stimulating hormone (FSH), and prolactin (PRL) signaling pathways may modulate the synthesis and secretion of gonadotropin-releasing hormone (GnRH), FSH, and luteinizing hormone (LH) within the hypothalamus and pituitary. In the ovary, interactions between granulosa cells and oocytes involved the KIT, CD99, LIFR, FN1, and ANGPTL signaling pathways, which collectively regulate follicular maturation. The SEMA4 signaling pathway emerged as a critical mediator across all three tissues of the HPO axis. Additionally, gene expression analysis revealed that relaxin 3 (RLN3), gastrin-releasing peptide (GRP), and cocaine- and amphetamine regulated transcripts (CART, also known as CARTPT) may function as novel endocrine hormones, influencing the HPO axis through autocrine, paracrine, and endocrine pathways. Comparative analyses between Lohmann layers and Liangshan Yanying chickens demonstrated higher expression levels of GRP, RLN3, CARTPT, LHCGR, FSHR, and GRPR in the ovaries of Lohmann layers, potentially contributing to their superior reproductive performance. In conclusion, this study provides a detailed molecular characterization of the HPO axis, offering novel insights into the regulatory mechanisms underlying reproductive biology.
Sujet(s)
Poulets , Axe hypothalamohypophysaire , Ovaire , Animaux , Femelle , Poulets/génétique , Poulets/physiologie , Ovaire/métabolisme , Axe hypothalamohypophysaire/métabolisme , Axe hypothalamohypophysaire/physiologie , RNA-Seq , Régulation de l'expression des gènes , Hypophyse/métabolisme , Transduction du signalRÉSUMÉ
Vitiligo is an acquired autoimmune skin disease characterized by patchy depigmentation of the skin, often accompanied by white hair. The aetiology of vitiligo is complex and difficult to cure, and its disfiguring appearance significantly impacts patients' mental and physical health. Psychological stress is a major factor in inducing and exacerbating vitiligo, as well as affecting its treatment efficacy, though the specific mechanisms remain unclear. Increasing research on the brain-skin axis in skin immunity suggests that psychological stress can influence local skin immunity through this axis, which may play a crucial role in the pathogenesis of vitiligo. This review focuses on the role of brain-skin axis in the pathogenesis of vitiligo, and explores the possible mechanism of brain-skin axis mediating the pathogenesis of vitiligo from the aspects of sympathetic nervous system, hypothalamic-pituitary-adrenal (HPA) axis and hormones and neuropeptides, aiming to provide the necessary theoretical basis for psychological intervention in the prevention and treatment of vitiligo.
Sujet(s)
Axe hypothalamohypophysaire , Axe hypophyso-surrénalien , Peau , Stress psychologique , Vitiligo , Vitiligo/psychologie , Vitiligo/thérapie , Humains , Axe hypothalamohypophysaire/métabolisme , Axe hypothalamohypophysaire/physiopathologie , Stress psychologique/immunologie , Stress psychologique/psychologie , Peau/anatomopathologie , Peau/immunologie , Axe hypophyso-surrénalien/métabolisme , Encéphale , Système nerveux sympathique/physiopathologie , Neuropeptides/métabolismeRÉSUMÉ
Like the ovaries and prostate, the thyroid exhibits characteristic hormone secretion and regulation. Thyroid cancer (TC), especially differentiated thyroid carcinoma, has typical sex-specific and age-specific hormone-driven clinical features. Previous research has primarily focused on the effects of thyroid stimulating hormone, thyroid hormones, and estrogens on the onset and progression of TC, while the roles of growth hormone (GH), androgens, and glucocorticoids have largely been overlooked. Similarly, few studies have investigated the interactions between hormones and hormone systems. In fact, numerous studies of patients with acromegaly have shown that serum levels of GH and insulin-like growth factor-1 (IGF-1) may be associated with the onset and progression of TC, although the influences of age, sex, and other risk factors, such as obesity and stress, remain unclear. Sex hormones, the GH/IGF axis, and glucocorticoids are likely involved in the onset and progression of TC by regulating the tumor microenvironment and metabolism. The aim of this review was to clarify the roles of hormones and hormone systems in TC, especially papillary thyroid carcinoma, as references for further investigations.
Sujet(s)
Axe hypothalamohypophysaire , Glande thyroide , Tumeurs de la thyroïde , Humains , Tumeurs de la thyroïde/métabolisme , Tumeurs de la thyroïde/anatomopathologie , Axe hypothalamohypophysaire/métabolisme , Glande thyroide/métabolisme , Hormones thyroïdiennes/métabolisme , Animaux , Facteur de croissance IGF-I/métabolismeRÉSUMÉ
BACKGROUND: The hypothalamic-pituitary-adrenal (HPA) and -gonadal (HPG) axes are two major pathways that connect the neural and endocrine systems in vertebrates. Factors such as prenatal stress and maternal exposure to exogenous steroids have been shown to affect these pathways during fetal development. Another less studied factor is the transfer of hormones across fetuses in multifetal pregnancies. This form of transfer has been shown to influence the morphology, anatomy, physiology, and behavior of the offspring in litter-bearing mammals, an influence termed the intrauterine position (IUP) effect. In this study, we sought to delineate how the IUP effects HPA and HPG brain receptors, peptides, and enzymes (hereafter components) in utero and how these influences may differ between males and females. METHODS: We utilized the unconventional model of culled free-ranging nutria (Myocastor coypus), with its large natural variation. We collected brain tissues from nutria fetuses and quantified the expression of key HPA and HPG components in three brain regions: prefrontal cortex, hypothalamus, and striatum. RESULTS: We found an interaction between sex and IUP in the mineralocorticoid receptor (MR), gonadotropin-releasing hormone receptor (GNRHR), androgen receptor (AR), and estrogen receptor alpha (ESR1). IUP was significant in both gonadotropin-releasing hormone (GnRH) and its receptor GNRHR, but in different ways. In the hypothalamus, fetuses adjacent to same-sex neighbors had higher expression of GnRH than fetuses neighboring the opposite sex. Conversely, in the cortex, GNRHR exhibited the inverse pattern, and fetuses that were neighboring the opposite sex had higher expression levels than those neighboring the same sex. Regardless of IUP, in most components that showed significant sex differences, female fetuses had higher mRNA expression levels than male fetuses. We also found that HPA and HPG components were highly related in the early stages of gestation, and that there was an interaction between sex and developmental stage. In the early stages of pregnancy, female component expression levels were more correlated than males', but in the last trimester of pregnancy, male components were more related to each other than female's. CONCLUSIONS: This study suggests that there are sexually different mechanisms to regulate the HPA and HPG axes during fetal development. Higher mRNA expression levels of endocrine axes components may be a mechanism to help females cope with prolonged androgen exposure over a long gestational period. Additionally, these findings suggest different coordination requirements of male and female endocrine axes during stages of fetal development.
Sujet(s)
ARN messager , Caractères sexuels , Femelle , Mâle , Animaux , ARN messager/métabolisme , ARN messager/génétique , Grossesse , Encéphale/métabolisme , Encéphale/embryologie , Axe hypothalamohypophysaire/métabolisme , Foetus/métabolisme , Axe hypophyso-surrénalien/métabolisme , Développement foetalRÉSUMÉ
Posttraumatic stress disorder (PTSD) is characterized by exposure to traumatic events and involves symptom domains such as intrusive thoughts, avoidant behaviors, negative mood, and cognitive dysfunction. The disorder can be chronic and debilitating, and the heterogenous nature and varied presentation of PTSD has afforded difficulty in determining efficacious treatment. The ability to identify biomarkers for PTSD risk, prognosis, or for the purposes of treatment, would be highly valuable. There is evidence for peripheral biomarkers related to the hypothalamic-pituitary-adrenal axis, the immune system, neurotransmitters and neurohormones, while genome and epigenome wide association studies have identified genes of interest relating to neurocircuitry, monoaminergic function, and the immune system. Importantly, however, reproducibility is a persistent issue. Considerations for future research include the need for well-powered and well-designed studies to determine directionality, in addition to considering biomarkers as they relate to symptom domains and the spectrum of symptom severity rather than dichotomous diagnostic outcomes. We conclude by recommending the staging of biological processes and PTSD symptoms, from subsyndromal to chronic, which could eventually facilitate selection of personalized treatment interventions for individuals with PTSD, in addition to serving as a future framework for biomarker data.
Sujet(s)
Marqueurs biologiques , Épigenèse génétique , Troubles de stress post-traumatique , Humains , Troubles de stress post-traumatique/génétique , Troubles de stress post-traumatique/diagnostic , Troubles de stress post-traumatique/métabolisme , Marqueurs biologiques/métabolisme , Système neuroendocrinien/métabolisme , Axe hypothalamohypophysaire/métabolisme , Transduction du signalRÉSUMÉ
The symptoms of post-traumatic stress disorder (PTSD) include re-experiencing trauma, avoidance behaviors, negative alterations in cognition and mood. However, the underlying molecular mechanisms are unclear. Dysfunction of hypothalamic-pituitary-adrenal axis (HPA-axis) and dysregulation of glutamatergic and GABAergic systems were shown during PTSD. Therefore, regulating hormonal change or glutamate energy metabolism are considered as a therapeutic approach to alleviate this condition. Herbal medicine may be effective in treating PTSD due to its ability to target multiple underlying mechanisms with various compounds. Hominis placenta (HP) is a traditional medicine widely used in East Asia for various conditions. However, the effect on PTSD has not been clarified. We aimed to investigate the effects of HP treatment in single-prolonged stress with shock (SPSS)-induced PTSD mice and explore its possible mechanisms. HP treatment at ST36 acupoints, combined with herbal medicine and acupuncture point stimulation, was applied three times/week for 2 weeks. HP treatment effectively alleviated anxiety and cognitive decline in SPSS-induced PTSD mice, as detected by Open field and the Y-maze test. Additionally, HP decreased the corticosterone levels and proinflammatory cytokines in the serum, modulated brain energy metabolism, and inhibited glutamate excitotoxicity, while regulating neuronal activity through modulating brain-derived neurotrophic factor (BDNF) levels, as demonstrated by western blot and immunohistochemistry, and flow cytometry analyses. These findings reveal that HP treatment effectively alleviates PTSD-like behaviors by regulating energy metabolism and neuronal activity though modulation of the HPA-axis and BDNF levels in PTSD mice, indicating that HP treatment is a promising therapeutic approach for PTSD.
Sujet(s)
Comportement animal , Métabolisme énergétique , Neurones , Troubles de stress post-traumatique , Animaux , Troubles de stress post-traumatique/métabolisme , Troubles de stress post-traumatique/traitement médicamenteux , Troubles de stress post-traumatique/psychologie , Métabolisme énergétique/effets des médicaments et des substances chimiques , Femelle , Souris , Grossesse , Mâle , Comportement animal/effets des médicaments et des substances chimiques , Neurones/métabolisme , Neurones/effets des médicaments et des substances chimiques , Placenta/métabolisme , Modèles animaux de maladie humaine , Facteur neurotrophique dérivé du cerveau/métabolisme , Anxiété/métabolisme , Anxiété/traitement médicamenteux , Corticostérone/sang , Axe hypothalamohypophysaire/métabolisme , Axe hypothalamohypophysaire/effets des médicaments et des substances chimiques , Cytokines/métabolismeRÉSUMÉ
Cortisol, a stress hormone, plays a crucial role in regulating metabolic, hemodynamic, inflammatory, and behavioral processes. Its secretion is governed by the hypothalamic-pituitary-adrenal axis. However, prolonged activation of this axis and increased cortisol bioavailability in tissues can result in detrimental metabolic effects. Chronic exposure to excessive cortisol is associated with insulin resistance and visceral obesity, both significant contributors to metabolic syndrome. This review delves into the regulation of the hypothalamic-pituitary-adrenal axis, the molecular mechanisms underlying cortisol synthesis and its actions, as well as the key factors influencing cortisol bioavailability. Furthermore, it provides a summary of available clinical research data on the involvement of cortisol in metabolic syndrome, alongside a discussion on the various biomatrices used for cortisol measurement in clinical settings.
Sujet(s)
Hydrocortisone , Axe hypothalamohypophysaire , Syndrome métabolique X , Humains , Syndrome métabolique X/métabolisme , Hydrocortisone/métabolisme , Axe hypothalamohypophysaire/métabolisme , Axe hypophyso-surrénalien/métabolismeRÉSUMÉ
In clinical endocrinology, it is often assumed that the results of thyroid hormone function tests (TFTs) before total thyroidectomy are considered euthyroid when the circulating concentrations of thyrotropin [TSH] and free thyroxine [FT4] are within the normal reference ranges. Postoperative thyroid replacement therapy with levothyroxine. The aim of L-T4 is to reproduce the preoperative euthyroid condition. Currently, intra-individual changes in the euthyroid set point before and after total thyroidectomy are only partly understood. After total thyroidectomy, a greater postoperative [FT4] than preoperative [FT4] for equivalent euthyroid [TSH] was found, with differences ranging from 3 to 8 pmol/L. This unexplained difference can be explained by the use of a mathematical model of the hypothalamus-pituitary-thyroid (HPT) axis set point theory. In this article, the postoperative HPT euthyroid set point was calculated using a dataset of total thyroidectomized patients with at least three distinguishable postoperative TFTs. The postoperative [TSH] set point was used as a homeostatic reference for the comparison of preoperative TFTs. The preoperative [FT4] value was equal to the postoperative [FT4] value in 50% of the patients, divided by a factor of ~ 1.25 (within +/- 10%). The factor of 1.25 stems from the lack of postoperative use of thyroidal triiodothyronine (T3). Furthermore, approximately 25% of the patients presented a greater preoperative [FT4] difference than postoperative [FT4]/1.25 combined with a normal [TSH] difference. Based on these observations, the effect of T3 on the value of the [FT4] set point was analyzed and explained from a control theory perspective.
Sujet(s)
Glande thyroide , Thyroïdectomie , Thyroxine , Tri-iodothyronine , Humains , Thyroxine/sang , Tri-iodothyronine/sang , Glande thyroide/chirurgie , Glande thyroide/métabolisme , Mâle , Femelle , Adulte d'âge moyen , Thyréostimuline/sang , Axe hypothalamohypophysaire/métabolisme , Tests de la fonction thyroïdienne/méthodes , Adulte , Hypophyse/métabolisme , Hypophyse/chirurgie , Sujet âgé , Hypothalamus/métabolismeRÉSUMÉ
Postpartum depression (PPD) affects 174 million women worldwide and is characterized by profound sadness, anxiety, irritability, and debilitating fatigue, which disrupt maternal caregiving and the mother-infant relationship. Limited pharmacological interventions are currently available. Our understanding of the neurobiological pathophysiology of PPD remains incomplete, potentially hindering the development of novel treatment strategies. Recent hypotheses suggest that PPD is driven by a complex interplay of hormonal changes, neurotransmitter imbalances, inflammation, genetic factors, psychosocial stressors, and hypothalamic-pituitary-adrenal (HPA) axis dysregulation. This narrative review examines recent clinical studies on PPD within the past 15 years, emphasizing advancements in neuroimaging findings and blood biomarker detection. Additionally, we summarize recent laboratory work using animal models to mimic PPD, focusing on hormone withdrawal, HPA axis dysfunction, and perinatal stress theories. We also revisit neurobiological results from several brain regions associated with negative emotions, such as the amygdala, prefrontal cortex, hippocampus, and striatum. These insights aim to improve our understanding of PPD's neurobiological mechanisms, guiding future research for better early detection, prevention, and personalized treatment strategies for women affected by PPD and their families.
Sujet(s)
Marqueurs biologiques , Dépression du postpartum , Humains , Dépression du postpartum/métabolisme , Femelle , Animaux , Axe hypophyso-surrénalien/métabolisme , Axe hypothalamohypophysaire/métabolisme , Encéphale/métabolisme , Encéphale/imagerie diagnostique , Stress psychologique/métabolismeRÉSUMÉ
Depressive pseudodementia (DPD) is a debilitating cognitive dysfunction that accompanies major and/or frequent depressive attacks. DPD has gained significant research attention owing to its negative effects on the patients' quality of life and productivity. This study tested the procognitive potential of Flibanserin (FBN), the serotonin (5HT) receptor modulator, against propranolol (PRP), as ß/5HT1A receptors blocker. Serving this purpose, female Wistar Albino rats were subjected to chronic unpredictable stress (CUS) and subsequently treated with FBN only (3 mg/kg/day, p.o), PRP only (10 mg/kg/day, p.o), or PRP followed by FBN, using the same doses. FBN ameliorated the behavioral/cognitive alterations and calmed the hypothalamic-pituitary-adrenal (HPA) axis storm by reducing the levels of stress-related hormones, viz, corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), corticosterone (CORT) parallel to epinephrine (EPI) hyperstimulation. The maladaptive inflammatory response, comprising of interleukin (IL)-1ß/6, and tumor necrosis factor (TNF)-α, was consequently blunted. This was contemporaneous to the partial restoration of the protein kinase-B (AKT)/glycogen synthase kinase (GSK)3ß/signal transducer and activator of transcription (STAT)-3 survival trajectory and the reinstatement of the levels of brain derived neurotrophic factor (BDNF). Microscopically, FBN repaired the hippocampal architecture and lessened CD68/GFAP immunoreactivity. Pre-administration of PRP partially abolished FBN effect along the estimated parameters, except for 5HT2A receptor expression and epinephrine level, to prove 5HT1A receptor as a fulcrum initiator of the investigated pathway, while its sole administration worsened the underlying condition. Ultimately, these findings highlight the immense procognitive potential of FBN, offering a new paradigm for halting DPD advancement via synchronizing adrenergic/serotonergic circuitry.
Sujet(s)
Benzimidazoles , Facteur neurotrophique dérivé du cerveau , Axe hypothalamohypophysaire , Axe hypophyso-surrénalien , Protéines proto-oncogènes c-akt , Rat Wistar , Animaux , Femelle , Rats , Comportement animal/effets des médicaments et des substances chimiques , Facteur neurotrophique dérivé du cerveau/métabolisme , Dépression/traitement médicamenteux , Dépression/métabolisme , Modèles animaux de maladie humaine , Axe hypothalamohypophysaire/effets des médicaments et des substances chimiques , Axe hypothalamohypophysaire/métabolisme , Inflammation/traitement médicamenteux , Inflammation/anatomopathologie , Inflammation/métabolisme , Axe hypophyso-surrénalien/effets des médicaments et des substances chimiques , Axe hypophyso-surrénalien/métabolisme , Protéines proto-oncogènes c-akt/métabolisme , Sérotonine/métabolisme , Transduction du signal/effets des médicaments et des substances chimiques , Stress psychologique/traitement médicamenteux , Stress psychologique/complications , Benzimidazoles/pharmacologie , Benzimidazoles/usage thérapeutiqueRÉSUMÉ
Multiple sclerosis (MS) is a chronic inflammatory disease that affects the central nervous system, usually diagnosed during the reproductive period. Both MS and its commonly used animal model, experimental autoimmune encephalomyelitis (EAE), exhibit sex-specific features regarding disease progression and disturbances in the neuroendocrine and endocrine systems. This study investigates the hypothalamic-pituitary-adrenal (HPA) axis response of male and female Dark Agouti rats during EAE. At the onset of EAE, Crh expression in the hypothalamus of both sexes is decreased, while males show reduced plasma adrenocorticotropic hormone levels. Adrenal gland activity is increased during EAE in both males and females, as evidenced by enlarged adrenal glands and increased StAR gene and protein expression. However, only male rats show increased serum and adrenal corticosterone levels, and an increased volume of the adrenal cortex. Adrenal 3ß-HSD protein and progesterone levels are elevated in males only. Serum progesterone levels of male rats are also increased, although testicular progesterone levels are decreased during the disease, implying that the adrenal gland is the source of elevated serum progesterone levels in males. Our results demonstrate a sex difference in the response of the HPA axis at the adrenal level, with male rats showing a more pronounced induction during EAE.
Sujet(s)
Encéphalomyélite auto-immune expérimentale , Axe hypothalamohypophysaire , Axe hypophyso-surrénalien , Animaux , Encéphalomyélite auto-immune expérimentale/métabolisme , Encéphalomyélite auto-immune expérimentale/anatomopathologie , Femelle , Mâle , Axe hypophyso-surrénalien/métabolisme , Rats , Axe hypothalamohypophysaire/métabolisme , Corticostérone/sang , Hormone corticotrope/sang , Glandes surrénales/métabolisme , Glandes surrénales/anatomopathologie , Caractères sexuels , Progestérone/sangRÉSUMÉ
Oxytocin can regulate immunological activity directly or indirectly; however, immunological functions and mechanisms of oxytocin actions under chronic stress like cesarean delivery (CD) are poorly understood. Our study found that abnormal oxytocin production and secretion in CD rats caused atrophy of thymic tissues. Neurotoxin kainic acid microinjected into the dorsolateral supraoptic nucleus in male rats selectively reduced hypothalamic oxytocin levels, increased corticotrophin-releasing hormone and plasma interleukin-1ß while reducing plasma oxytocin, thyroxine and testosterone levels and causing atrophy of immune tissues. Thus, plasma oxytocin is essential for immunological homeostasis, which involves oxytocin facilitation of thyroid hormone and sex steroid secretion.
Sujet(s)
Axe hypothalamohypophysaire , Ocytocine , Animaux , Ocytocine/sang , Ocytocine/métabolisme , Rats , Mâle , Axe hypothalamohypophysaire/effets des médicaments et des substances chimiques , Axe hypothalamohypophysaire/métabolisme , Femelle , Rat Sprague-Dawley , Acide kaïnique/toxicité , Interleukine-1 bêta/métabolisme , Interleukine-1 bêta/sang , Testostérone/sang , Corticolibérine/métabolisme , Thymus (glande)/effets des médicaments et des substances chimiques , Thymus (glande)/métabolismeRÉSUMÉ
RATIONALE: Premenstrual dysphoric disorder (PMDD) is characterized by severe affective symptoms during the luteal phase of the menstrual cycle. There is some evidence of altered interactions between the hypothalamic pituitary gonadal (HPG) and hypothalamic pituitary adrenal (HPA) axes in PMDD. There is also evidence that similar affective disorders such as major depression and perinatal depression are associated with dysregulation in immune factors, but this has not been characterized in PMDD. AIMS: The goals of this exploratory study were to identify 1) whether HPA-HPG axis interactions and immune markers differ between PMDD patients and controls across the menstrual cycle; 2) how luteal phase sertraline treatment impacts stress and inflammatory markers. METHODS: Participants were females age 18-50 with regular menstrual cycles, not using psychotropic or hormonal medications, and were assigned to a control group or PMDD group based on prospective daily symptom ratings and clinical interview. Blood was drawn in the follicular and luteal phases, during laboratory sessions involving a mildly stressful task. In a second luteal phase, PMDD participants received open-label sertraline (50â¯mg/d) from ovulation to menses. Serum cortisol and ACTH were measured via ELISA and operationalized as area under the curve with respect to ground (AUCg), and peak level following laboratory task. Serum TNF-α, IL-6, CXCL-8, and IL-1ß were measured using multiplex kits. Serum allopregnanolone (ALLO) was measured by gas chromatography/mass spectroscopy. To characterize HPA-HPG axis interactions across the menstrual cycle in PMDD participants and controls, multilevel linear models predicted cortisol and ACTH from the interaction of cycle phase (controlling for sertraline treatment), ALLO, and group. To determine the effects of sertraline treatment on inflammatory markers and how groups might differ in cyclical change on each marker, multilevel linear models predicted inflammatory markers from cycle phase (controlling for sertraline treatment) and group. A final set of exploratory models tested whether inflammatory markers predict premenstrual symptom score severity. RESULTS: The sample included n=77 participants (41 controls, 36 PMDD); 28 participants with PMDD completed sertraline treatment. Group x phase x ALLO interactions showed that higher ALLO levels predicted lower cortisol peak in the treated luteal phase (interaction between phase and ALLO, p=0.042), and there was a higher cortisol peak in the treated luteal phase than the untreated luteal phase (p=0.038). CXCL-8 was significantly associated with premenstrual symptom severity after controlling for group and cycle phase (p=0.011). There were no main effects of group, phase, or ALLO on cortisol AUCg, ACTH AUCg, IL-6, CXCL-8, IL-1ß, nor TNF-α (p's>0.05). CONCLUSION: Serum markers of HPA axis and immune function did not vary by menstrual cycle phase nor PMDD status. However, sertraline treatment in the luteal phase was associated with higher ALLO levels predicting lower cortisol peak in response to mild laboratory stress, suggesting that sertraline treatment may normalize HPG-HPA axis interactions among individuals with PMDD. Greater premenstrual symptomatology was associated with higher levels of the inflammatory marker CXCL-8, but further research is needed into the potential role of inflammation in PMDD.
Sujet(s)
Axe hypothalamohypophysaire , Inflammation , Phase lutéale , Axe hypophyso-surrénalien , Trouble dysphorique prémenstruel , Sertraline , Humains , Femelle , Adulte , Axe hypothalamohypophysaire/métabolisme , Axe hypothalamohypophysaire/effets des médicaments et des substances chimiques , Sertraline/usage thérapeutique , Axe hypophyso-surrénalien/métabolisme , Axe hypophyso-surrénalien/effets des médicaments et des substances chimiques , Trouble dysphorique prémenstruel/métabolisme , Trouble dysphorique prémenstruel/traitement médicamenteux , Jeune adulte , Inflammation/métabolisme , Inflammation/traitement médicamenteux , Adulte d'âge moyen , Adolescent , Marqueurs biologiques/sang , Hydrocortisone/sang , Hydrocortisone/métabolismeRÉSUMÉ
BACKGROUND: The relationship between neurotransmitters and oxidative stress in Major Depressive Disorder (MDD) patients, considering HPA axis activity and psychological and cognitive states, is unclear. This study examines changes in neurotransmitters (GABA, Glx) and antioxidants (GSH) in the dorsal anterior cingulate cortex (dACC) of MDD patients under varying levels of ACTH, and their relationship with psychological and cognitive conditions. METHODS: Forty-five MDD patients were divided into high-ACTH (>65 pg/mL; n = 16) and normal-ACTH (7-65 pg/mL; n = 29) groups based on blood ACTH levels, along with 12 healthy controls (HC). All participants underwent HAM-D, HAM-A assessments, and most completed MMSE and MoCA tests. GABA+, Glx, and GSH levels in the dACC were measured using the MEGA-PRESS sequence. Intergroup differences and correlations between clinical factors, HPA axis activity, and metabolites were analyzed. RESULTS: Compared to HC, the normal ACTH group showed higher Glx and lower GSH levels. Glx and GSH were negatively correlated with MDD severity. In the high-ACTH MDD group, Glx positively correlated with delayed memory, and GSH positively correlated with abstraction. Factors influencing GABA included ACTH levels, depression duration, and negative events. Predictive factors for HAM-D scores were GSH and GABA. LIMITATIONS: The sample size is small. CONCLUSION: MDD patients exhibit neurochemical differences in the brain related to HPA axis levels, MDD severity, and cognitive function. Clinical factors, neurotransmitters, and neuroendocrine levels significantly influence depression severity.
Sujet(s)
Hormone corticotrope , Antioxydants , Trouble dépressif majeur , Gyrus du cingulum , Agents neuromédiateurs , Acide gamma-amino-butyrique , Humains , Trouble dépressif majeur/sang , Trouble dépressif majeur/métabolisme , Trouble dépressif majeur/physiopathologie , Hormone corticotrope/sang , Femelle , Mâle , Adulte , Antioxydants/métabolisme , Acide gamma-amino-butyrique/métabolisme , Acide gamma-amino-butyrique/sang , Adulte d'âge moyen , Agents neuromédiateurs/sang , Agents neuromédiateurs/métabolisme , Gyrus du cingulum/métabolisme , Glutathion/sang , Glutathion/métabolisme , Axe hypothalamohypophysaire/métabolisme , Axe hypothalamohypophysaire/physiopathologie , Axe hypophyso-surrénalien/métabolisme , Axe hypophyso-surrénalien/physiopathologie , Stress oxydatif/physiologie , Études cas-témoinsRÉSUMÉ
Excessive stress can exceed the adjustment ability of body and cause injury and dysfunction, while elucidation of the mechanism and prevention measures of stress-related injury are still insufficient. The present study was to observe the effect of glucocorticoid (GC) on stress-induced hypothalamic nerve injury and elucidate the potential mechanism. The present study intended to establish a chronic restraint stress rat model for follow-up study. Open field test and elevated plus maze test were used to observe behavioral changes of stress rats; Enzyme-linked immunosorbent assay (ELISA) was used to detect changes in the levels of hypothalamus-pituitary-adrenal (HPA) axis-related hormones and inflammatory factors in hypothalamus; toluidine blue staining was used to observe pathological changes of hypothalamus. The results showed that stress rats showed obvious anxiety-like behaviors, the levels of HPA axis-related hormones and inflammatory factors showed abnormal fluctuations, and morphological results showed significant nerve injury in hypothalamus. Low-dose GC treatment significantly improved behavioral changes, alleviated hypothalamic nerve injury, and restored hypothalamic levels of inflammatory factors, serum levels of GC, corticotropin-releasing hormone (CRH), and adrenocorticotropic hormone (ACTH) and GC level in adrenal cortex of stressed rats, while GC receptor (GR) inhibitor, CRH receptor inhibitor, and adrenalectomy reversed the ameliorative effects of low-dose GC. Our study clarified that low-dose GC can restore stress coping ability by reshaping the homeostasis of the HPA axis, thus alleviating behavioral abnormalities and hypothalamic nerve injury in stressed rats.
Sujet(s)
Hormone corticotrope , Glucocorticoïdes , Homéostasie , Axe hypothalamohypophysaire , Hypothalamus , Axe hypophyso-surrénalien , Rat Sprague-Dawley , Stress psychologique , Animaux , Axe hypothalamohypophysaire/effets des médicaments et des substances chimiques , Axe hypothalamohypophysaire/métabolisme , Axe hypophyso-surrénalien/effets des médicaments et des substances chimiques , Axe hypophyso-surrénalien/métabolisme , Mâle , Rats , Glucocorticoïdes/pharmacologie , Stress psychologique/traitement médicamenteux , Stress psychologique/métabolisme , Homéostasie/effets des médicaments et des substances chimiques , Homéostasie/physiologie , Hormone corticotrope/sang , Hypothalamus/effets des médicaments et des substances chimiques , Hypothalamus/métabolisme , Corticolibérine/métabolisme , Corticolibérine/pharmacologie , Modèles animaux de maladie humaine , Comportement animal/effets des médicaments et des substances chimiquesRÉSUMÉ
Posttraumatic stress disorder (PTSD) is a pervasive issue within military populations, with approximately 29â¯% of post-9/11 service members experience PTSD at some point in their lifetime. One potentially important factor in PTSD development and treatment response is dysregulation of the stress response system stemming from exposure to multiple traumas and sustained operational stress associated with military training and deployment. In particular, the end-product of the hypothalamic-pituitary-adrenal (HPA) axis, cortisol, is of particular interest to researchers examining physiological stress response in the context of mental health. Research exploring cortisol has been ongoing for decades, both to further understand its pathways and mechanisms, and to develop potential novel PTSD treatments. This paper provides a narrative review of some of the published literature examining cortisol's role in PTSD as a potential factor in development, maintenance, and treatment augmentation, with emphasis on military populations. The results of this review highlight the importance of exploring alterations to the stress response system, and cortisol in particular, for the evaluation and treatment of PTSD in the military, the need for more comprehensive work towards understanding development of these alterations through military training and service, and its impact on long-term PTSD outcomes.
Sujet(s)
Hydrocortisone , Axe hypothalamohypophysaire , Personnel militaire , Axe hypophyso-surrénalien , Troubles de stress post-traumatique , Humains , Troubles de stress post-traumatique/métabolisme , Troubles de stress post-traumatique/thérapie , Troubles de stress post-traumatique/physiopathologie , Hydrocortisone/métabolisme , Personnel militaire/psychologie , Axe hypothalamohypophysaire/métabolisme , Axe hypophyso-surrénalien/métabolisme , Stress psychologique/métabolismeRÉSUMÉ
INTRODUCTION: Cortisol is a biological marker of stress, and its levels reflect the hypothalamic-pituitary-adrenal (HPA) axis response to stress over time. Saliva, blood, and urine cortisol reflect acute stress, whereas assessment of hair cortisol is a better reflection of chronic stress. There is limited information on hair cortisol concentration (HCC) in the perinatal period, particularly, in the preconception and postpartum periods. In addition to being a biomarker for stress, high levels of cortisol are typically associated with poor psychosocial outcomes, and adverse pregnancy outcomes. The objectives of this study were: (1) to measure HCC from six months preconception to six months postpartum; (2) to examine the relationship between HCC and demographic characteristics, depressive symptoms, and perceived stress in the first six months postpartum period; (3) and to assess the associations between HCC and systemic inflammatory markers in the first six months postpartum. METHODS: The analysis included 96 women from a longitudinal study with up to 3 study visits in the first six months postpartum. Blood and hair samples were collected at 1-2 months (PP1), 3-4 months (PP2), and 5-6 months (PP3) postpartum. We obtained sociodemographic information, depressive symptoms, and perceived stress scores at PP1-PP3. To quantify cortisol levels over time, 8 segments were derived corresponding to 6 (PC1) and 3 (PC2) months preconception as well as for each trimester (T1-T3) and postpartum (PP1-PP3). Eight cytokines (Granulocyte-macrophage colony-stimulating factor (GM-CSF), Interferon- gamma [IFN- γ], Interleukin [IL]-10, IL-2, IL-4, IL-6, IL-8, and Tumor necrosis factor-alpha (TNF- α) were measured in plasma in the postpartum samples. Univariate, bivariate, correlations, and linear mixed modelling were performed using SAS 9.4. Multiple testing correction was conducted for correlations using false discovery rate and a Q value of <0.05 was deemed significant. RESULTS: Median HCC varied over time peaking in the third trimester and declining in the postpartum. Significant differences were noted in median cortisol levels by race with Black/African American postpartum women experiencing higher levels at all timepoints. Significantly, higher median cortisol levels were also observed at PP1 and PP2 for mothers who reported their relationship status as single. Ethnicity, education, median age, depressive symptoms, and perceived stress were not associated with median cortisol levels. Pro-inflammatory cytokines IFN- γ (q= 0.01; r=-0.50) and IL-8 (q= 0.00; r=-0.55) showed correlations with HCC at PP1. CONCLUSION: HCC increased during pregnancy, peaking at T3 and declining PP consistent with previous work. Black/African American women and single women have significantly higher median cortisol levels in the postpartum period. The marked increase of HCC in Black women may be an important factor in understanding maternal health racial inequities. Future studies should investigate how the relationships between HCC, sociodemographics, and systemic cytokines impact perinatal outcomes.
Sujet(s)
Poils , Hydrocortisone , Période du postpartum , Stress psychologique , Humains , Femelle , Poils/composition chimique , Hydrocortisone/analyse , Hydrocortisone/métabolisme , Période du postpartum/métabolisme , Période du postpartum/psychologie , Adulte , Grossesse , Stress psychologique/métabolisme , Études longitudinales , Dépression/métabolisme , Marqueurs biologiques/analyse , Axe hypothalamohypophysaire/métabolisme , Jeune adulte , Axe hypophyso-surrénalien/métabolismeRÉSUMÉ
BACKGROUND: Stress during pregnancy can lead to adverse maternal and infant health outcomes through epigenetic changes in the hypothalamic-pituitary-adrenal axis. Among farmers in low-income countries, one important stressor is food insecurity, which can be reduced using hermetic storage bags. This study aimed to determine, for the first time, whether a hermetic storage bag intervention during pregnancy positively affects maternal and infant DNA methylation of the hypothalamic-pituitary-adrenal axis-related genes FKBP5 and NR3C1. We further analyzed whether anthropometrics, stress, and mental health were associated with DNA methylation. METHODS: This study was part of a larger matched-pair randomized controlled trial focusing on the impact of improved on-farm storage on food security, poverty, and net income of smallholder farming households. A total of N = 149 mothers were recruited by telephone and invited to attend a study appointment at health facilities in Kakamega County, Western Kenya, with their infants in April or May 2021. During the appointment, anthropometric measurements were taken, questionnaires on stress and mental health were administered, and saliva samples were collected. Logistic and multiple linear regression were used to examine the effect of the intervention and related measures on DNA methylation. RESULTS: Mothers in the intervention group showed higher mean NR3C1 methylation levels than those in the control group, corrected for multiple testing. Maternal postpartum body mass index was positively associated with infant NR3C1 CpG3 DNA methylation. The more stressful life events a mother had experienced in the previous 12 months (including during pregnancy), the lower her FKBP5 CpG3 methylation levels. CONCLUSIONS: Food insecurity and stressful life events during pregnancy seem to exert significant effects on maternal DNA methylation. While these stressors did not appear to impact infant DNA methylation in the present study, maternal postpartum body mass index was significantly related to infant methylation. These findings suggest that while infants may be protected from excessive maternal glucocorticoids by placental barrier activity, maternal metabolic status is still reflected in their epigenetic make-up. Trial registration This study was part of a larger matched-pair randomized controlled trial on the impact of improved on-farm crop storage on welfare, nutrition, and human health. Registration can be found in the American Economic Association (AEA) RCT Registry, RCT ID: AEARCTR-0005845.
Sujet(s)
Méthylation de l'ADN , Épigenèse génétique , Récepteurs aux glucocorticoïdes , Humains , Méthylation de l'ADN/génétique , Femelle , Kenya , Adulte , Grossesse , Nourrisson , Récepteurs aux glucocorticoïdes/génétique , Récepteurs aux glucocorticoïdes/métabolisme , Protéines de liaison au tacrolimus/génétique , Mères/psychologie , Mâle , Stress psychologique/génétique , Fermes , Axe hypothalamohypophysaire/métabolisme , Jeune adulte , Insécurité alimentaire , Axe hypophyso-surrénalien/métabolisme , Nouveau-né , Produits agricoles/génétiqueRÉSUMÉ
Background: It has been reported that central adrenal insufficiency (CAI) in pediatric patients (pts) with Prader-Willi syndrome (PWS) may be a potential cause of their sudden death. In addition, the risk of CAI may increase during treatment with recombinant human growth hormone (rhGH). Objective: To prevent both over- and undertreatment with hydrocortisone, we evaluated the prevalence of CAI in a large multicenter cohort of pediatric pts with PWS analyzing adrenal response in the low-dose ACTH test (LDAT) and/or the glucagon stimulation test (GST) and reviewing the literature. Methods: A total of 46 pts with PWS were enrolled to the study, including 34 treated with rhGH with a median dose of 0.21 mg/kg/week. LDAT was performed in 46 pts, and GST was carried out in 13 pts. Both tests were conducted in 11 pts. The tests began at 8:00 a.m. Hormones were measured by radioimmunoassays. Serum cortisol response >181.2 ng/mL (500 nmol/L) in LDAT and >199.3 ng/mL (550 nmol/L) in GST was considered a normal response. Additionally, cortisol response delta (the difference between baseline and baseline) >90 ng/mL and doubling/tripling of baseline cortisol were considered indicators of normal adrenal reserve. Results: Three GSTs were not diagnostic (no hypoglycemia obtained). LDAT results suggested CAI in four pts, but in two out of four pts, and CAI was excluded in GST. GST results suggested CAI in only one patient, but it was excluded in LDAT. Therefore, CAI was diagnosed in 2/46 pts (4.3%), 1 treated and 1 untreated with rhGH, with the highest cortisol values of 162 and 175 ng/dL, but only in one test. However, in one of them, the cortisol delta response was >90 ng/mL and peak cortisol was more than tripled from baseline. Finally, CAI was diagnosed in one patient treated with rhGH (2.2%). Conclusion: We present low prevalence of CAI in pediatric pts with PWS according to the latest literature. Therefore, we do not recommend to routinely screen the function of the hypothalamic-pituitary-adrenal axis (HPAA) in all pts with PWS, both treated and untreated with rhGH. According to a review of the literature, signs and symptoms or low morning ACTH levels suggestive of CAI require urgent and appropriate diagnosis of HPAA by stimulation test. Our data indicate that the diagnosis of CAI should be confirmed by at least two tests to prevent overtreatment with hydrocortisone.
Sujet(s)
Hydrocortisone , Axe hypothalamohypophysaire , Axe hypophyso-surrénalien , Syndrome de Prader-Willi , Humains , Syndrome de Prader-Willi/traitement médicamenteux , Syndrome de Prader-Willi/sang , Syndrome de Prader-Willi/complications , Femelle , Mâle , Axe hypothalamohypophysaire/effets des médicaments et des substances chimiques , Axe hypothalamohypophysaire/métabolisme , Axe hypophyso-surrénalien/effets des médicaments et des substances chimiques , Axe hypophyso-surrénalien/métabolisme , Enfant , Enfant d'âge préscolaire , Hydrocortisone/sang , Adolescent , Insuffisance surrénale/diagnostic , Insuffisance surrénale/sang , Insuffisance surrénale/traitement médicamenteux , Insuffisance surrénale/épidémiologie , Nourrisson , Hormone de croissance humaine/sang , Hormone corticotrope/sang , Hormone corticotrope/administration et posologie , Glucagon/sangRÉSUMÉ
Fibromyalgia (FM) is a central disorder characterized by chronic pain, fatigue, insomnia, depression, and other minor symptoms. Knowledge about pathogenesis is lacking, diagnosis difficult, clinical approach puzzling, and patient management disappointing. We conducted a theoretical study based on literature data and computational analysis, aimed at developing a comprehensive model of FM pathogenesis and addressing suitable therapeutic targets. We started from the evidence that FM must involve a dysregulation of central pain processing, is female prevalent, suggesting a role for the hypothalamus-pituitary-gonadal (HPG) axis, and is stress-related, suggesting a role for the HP-adrenocortical (HPA) axis. Central pathogenesis was supposed to involve a pain processing loop system including the thalamic ventroposterolateral nucleus (VPL), the primary somatosensory cortex (SSC), and the thalamic reticular nucleus (TRN). For decreasing GABAergic and/or increasing glutamatergic transmission, the loop system crosses a bifurcation point, switching from monostable to bistable, and converging on a high-firing-rate steady state supposed to be the pathogenic condition. Thereafter, we showed that GABAergic transmission is positively correlated with gonadal-hormone-derived neurosteroids, notably allopregnanolone, whereas glutamatergic transmission is positively correlated with stress-induced glucocorticoids, notably cortisol. Finally, we built a dynamic model describing a multistable, double-inhibitory loop between HPG and HPA axes. This system has a high-HPA/low-HPG steady state, allegedly reached in females under combined premenstrual/postpartum brain allopregnanolone withdrawal and stress condition, driving the thalamocortical loop to the high-firing-rate steady state, and explaining the connection between endocrine and neural mechanisms in FM pathogenesis. Our model accounts for FM female prevalence and stress correlation, suggesting the use of neurosteroid drugs as a possible solution to currently unsolved problems in the clinical treatment of the disease.