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Frontiers in Endocrinology 2024Spexin (SPX, NPQ) is a 14-amino acid neuroactive peptide identified using bioinformatics. This amino acid sequence of the mature spexin peptide has been highly conserved... (Review)
Review
Spexin (SPX, NPQ) is a 14-amino acid neuroactive peptide identified using bioinformatics. This amino acid sequence of the mature spexin peptide has been highly conserved during species evolution and is widely distributed in the central nervous system and peripheral tissues and organs. Therefore, spexin may play a role in various biological functions. Spexin, the cognate ligand for GALR2/3, acting as a neuromodulator or endocrine signaling factor, can inhibit reproductive performance. However, controversies and gaps in knowledge persist regarding spexin-mediated regulation of animal reproductive functions. This review focuses on the hypothalamic-pituitary-gonadal axis and provides a comprehensive overview of the impact of spexin on reproduction. Through this review, we aim to enhance understanding and obtain in-depth insights into the regulation of reproduction by spexin peptides, thereby providing a scientific basis for future investigations into the molecular mechanisms underlying the influence of spexin on reproductive function. Such investigations hold potential benefits for optimizing farming practices in livestock, poultry, and fish industries.
Topics: Animals; Reproduction; Peptide Hormones; Vertebrates; Humans; Hypothalamo-Hypophyseal System
PubMed: 38915898
DOI: 10.3389/fendo.2024.1422711 -
Dermatology and Therapy Jun 2024Chronic pruritus (CP) is defined as an unpleasant sensation causing a desire to scratch and lasting > 6 weeks. It has a multifactorial etiology but is more frequently... (Review)
Review
Chronic pruritus (CP) is defined as an unpleasant sensation causing a desire to scratch and lasting > 6 weeks. It has a multifactorial etiology but is more frequently associated with chronic inflammatory dermatoses and systemic disorders. Psychogenic pruritus and neurological disorders are other less common etiologies, while, in some patients, it is idiopathic. CP appears to be processed by non-histaminergic pathway, contributing to its complexity and therapeutic challenge. Moreover, regardless of the etiology, it is multidimensional, including cognitive, motivational and affective components. There is a close link between psychological distress and pruritus, with particular clinical expression in chronic inflammatory dermatoses, involving the activation of the hypothalamic-pituitary-adrenal axis (and its cutaneous equivalent), the sympathetic nervous system, the release of hormones and peptides, the role of immune cells (T and B cells, macrophages) and immune-related cells in the skin (mast cells, dendritic cells and keratinocytes). Moreover, there is strong evidence that psychological factors influence the experience of pruritus. CP can also cause psychiatric disorders, including but not limited to anxiety and depression, and also lead to significant quality of life (QoL) impairment. Thereby, although a psychodermatological assessment should ideally be carried out in the context of a specific psychodermatology consultation, a brief mental health assessment could be part of the general dermatological approach to these patients. Considering that mental health, QoL and pruritus are closely linked, psychotherapeutic interventions and/or psychotropic drugs should thus be considered in some patients as an adjunct to the pharmacological treatment of CP.
PubMed: 38914907
DOI: 10.1007/s13555-024-01214-z -
ENeuro Jun 2024Epilepsy is often comorbid with psychiatric illnesses, including anxiety and depression. Despite the high incidence of psychiatric comorbidities in people with epilepsy,...
Epilepsy is often comorbid with psychiatric illnesses, including anxiety and depression. Despite the high incidence of psychiatric comorbidities in people with epilepsy, few studies address the underlying mechanisms. Stress can trigger epilepsy and depression. Evidence from human and animal studies support that hypothalamic-pituitary-adrenal (HPA) axis dysfunction may contribute to both disorders as well as their comorbidity (Kanner, 2003). Here, we investigate if HPA axis dysfunction may influence epilepsy outcomes and psychiatric comorbidities. We generated a novel mouse model (/ KO mice) lacking the K/Cl co-transporter, KCC2, in corticotropin-releasing hormone (CRH) neurons, which exhibit stress- and seizure-induced HPA axis hyperactivation (Melon et al., 2018). We used the / KO mice to examine the impact on epilepsy outcomes, including seizure frequency/burden, comorbid behavioral deficits, and SUDEP risk. We found sex differences in HPA axis dysfunction's effect on chronically epileptic KCC2/Crh KO mice seizure burden, vulnerability to comorbid behavioral deficits, and SUDEP. Suppressing HPA axis hyperexcitability in this model using pharmacological or chemogenetic approaches decreased SUDEP incidence, suggesting that HPA axis dysfunction may contribute to SUDEP. Altered neuroendocrine markers were present in SUDEP cases compared to people with epilepsy or individuals without epilepsy. Together, these findings implicate HPA axis dysfunction in the pathophysiological mechanisms contributing to psychiatric comorbidities in epilepsy and SUDEP. Our work provides new insight into a potential novel pathophysiological mechanism contributing to psychiatric illnesses and SUDEP in epilepsy patients, implicating HPA axis dysfunction in negative outcomes associated with epilepsy. This study is the first to link HPA axis dysfunction to SUDEP risk. Chronically epileptic male mice with exaggerated HPA axis dysfunction had increased SUDEP incidence. The translational relevance of these findings is supported by neuroendocrine abnormalities observed in postmortem samples from individuals that died of SUDEP. These data suggest that neuroendocrine mechanisms should be further explored in psychiatric comorbidities in epilepsy and SUDEP risk. Further, neuroendocrine markers may be a biomarker for SUDEP risk.
PubMed: 38914464
DOI: 10.1523/ENEURO.0162-24.2024 -
General and Comparative Endocrinology Jun 2024The physiological processes in animal production are regulated through biologically active molecules like peptides, proteins, and hormones identified through the... (Review)
Review
The physiological processes in animal production are regulated through biologically active molecules like peptides, proteins, and hormones identified through the development of the fundamental sciences and their application. One of the main polypeptides that plays an essential role in regulating physiological responses is the pituitary adenylate cyclase-activating polypeptide (PACAP). PACAP belongs to the glucagon/growth hormone-releasing hormone (GHRH)/vasoactive intestinal proteins (VIP) family and regulates feed intake, stress, and immune response in birds. Most of these regulations occur after PACAP stimulates the cAMP signaling pathway, which can regulate the expression of genes like MuRF1, FOXO1, Atrogin 1, and other ligases that are essential members of the ubiquitin system. On the other hand, PACAP stimulates the secretion of CRH in response to stress, activating the ubiquitin signaling pathway that plays a vital role in protein degradation and regulates oxidative stress and immune responses. Many studies conducted on rodents, mammals, and other models confirm the regulatory effects of PACAP, cAMP, and the ubiquitin pathway; however, there are no studies testing whether PACAP-induced cAMP signaling in poultry regulates the ubiquitin pathway. Besides, it would be interesting to investigate if PACAP can regulate ubiquitin signaling during stress response via CRH altered by HPA axis stimulation. Therefore, this review highlights a summary of research studies that indicate the potential interaction of the PACAP and ubiquitin signaling pathways on different molecular and physiological parameters in poultry species through the cAMP and stress signaling pathways.
PubMed: 38914296
DOI: 10.1016/j.ygcen.2024.114577 -
The Journal of Endocrinology Jun 2024
Topics: Animals; Mice; Signal Transduction; Liver; Epidermal Growth Factor; Growth Hormone
PubMed: 38914116
DOI: 10.1530/JOE-09-0372e -
American Journal of Clinical Pathology Jun 2024The incidence of pituitary neuroendocrine tumors has been reported high at autopsy. This study aimed to detect many tumors in both anterior and posterior lobes to prove...
OBJECTIVES
The incidence of pituitary neuroendocrine tumors has been reported high at autopsy. This study aimed to detect many tumors in both anterior and posterior lobes to prove tumor histogenesis.
METHODS
In total, 150 pituitary glands were studied from the University of Kansas Medical Center from 1995 to 2000. The pituitary gland was sagittally sliced from anterior to posterior into 6 to 8 sections. When H&E-stained sections revealed tumors, the tumors were immunohistochemically stained for 6 pituitary hormones.
RESULTS
Among 150 autopsy cases, 38 (25.3%) harbored microadenomas, including 4 cases with double tumors. Twenty-three (54.7%) cases were negative to all pituitary hormones. Of the remaining 19 tumors, 13 (30.9%) were lactotrophs, with 4 cases being concomitantly somatotrophs and gonadotrophs, and 2 cases were corticotropes. More than 85% of pituitary neuroendocrine tumors were adjacent to the capsule. Thirteen (8.7%) granular cell pituicytomas were found in the posterior lobe. There were pituicytes transforming into granular cell tumors.
CONCLUSIONS
The incidence was 25.3% for pituitary neuroendocrine tumors and 8.7% for granular cell pituicytomas. Since most pituitary neuroendocrine tumors were adjacent to the pituitary capsule, the capsule appeared to be the germinal center. Both pituitary tumors belonged to the 2 different transcription factor lineages.
PubMed: 38913876
DOI: 10.1093/ajcp/aqae067 -
The Journal of Clinical Endocrinology... Jun 2024The 2019 AACE guidelines suggested peak GH-cutoffs to glucagon test (GST) of ≤3 µg/L and ≤1 µg/L in the diagnosis of permanent GH deficiency (GHD) during the...
CONTEXT
The 2019 AACE guidelines suggested peak GH-cutoffs to glucagon test (GST) of ≤3 µg/L and ≤1 µg/L in the diagnosis of permanent GH deficiency (GHD) during the transition phase.
OBJECTIVE
Aim of the study was to evaluate the accuracy of GST compared to insulin tolerance test (ITT) in the definition of GHD at adult height achievement.
PATIENTS AND METHODS
Ninety-seven subjects with childhood-onset GHD (median age, 17.39 years) underwent ITT, GST and IGF-1 testing; 44 subjects were idiopathic (isolated GHD), 35 moderate organic GHD (0-2 hormone deficiencies-HDs) and 18 severe organic GHD (≥3 HDs).
RESULTS
Bland and Altman analysis showed a high consistency of GH peak measures after ITT and GST. Receiver operating characteristic analysis-ROC- identified 7.3 μg/L as the optimal GH peak cutoff to GST (95% CI 4.15-8.91; sensitivity 95.7%, specificity 88.2%, positive predictive value-PPV-88.0%, negative predictive value-NPV-95.7%), able to correctly classify 91.8% of the entire cohort while 5.8 μg/L was the best GH peak cutoff able to correctly classify 91.4% of moderate organic GHD patients (95% CI 3.16-7.39; sensitivity 96.0%, specificity 80.0%, PPV 92.3%, NPV 88.9%). Patients with ≥3HDs showed a GH peak <5μg/L at ITT and <5.8μg/L at GST but one. The optimal cutoff for IGF1 was -1.4 SDS (95% CI -1.94-0.77; sensitivity 75%, specificity 94%, PPV 91.7%, NPV 81.0%) that correctly classified 85.1% of the study population.
CONCLUSIONS
A GH peak to GST <5.8 μg/L represents an accurate diagnostic cutoff for young adults with childhood-onset GHD and high pre-test probability of permanent GHD.
PubMed: 38913686
DOI: 10.1210/clinem/dgae408 -
Cureus May 2024Destructive thyroiditis and secondary adrenal insufficiency are major endocrinological immune-related adverse events of immune checkpoint inhibitors (ICIs). However, the...
Destructive thyroiditis and secondary adrenal insufficiency are major endocrinological immune-related adverse events of immune checkpoint inhibitors (ICIs). However, the timing at which each event occurs most frequently after drug administration varies, and cases where multiple events occur simultaneously are rare. We encountered a patient who concurrently suffered from thyrotoxicosis and adrenal insufficiency. An 80-year-old woman with a history of type 2 diabetes mellitus (DM) was diagnosed with stage IVA squamous cell carcinoma of the lungs. Treatment with a combination of nivolumab and ipilimumab was initiated. Although she tested positive for thyroglobulin antibody and transient subclinical hyperthyroidism was observed after two courses, treatment with ICIs was continued. Four months later, treatment was discontinued due to drug-induced lung disease. One month after the last administration, the patient became unconscious and was admitted to another hospital, diagnosed with diabetic ketoacidosis, urinary tract infection, and sepsis. After acute-phase treatment, she was transferred to our hospital due to persistent fever and tachycardia. Thyrotoxicosis and adrenal insufficiency were observed, with high levels of free thyroxine, low thyroid-stimulating hormone (TSH), and cortisol levels. Treatment with extracellular fluids, potassium iodide, beta-blockers, and hydrocortisone was initiated, and the patient's condition improved. No other pituitary hormone deficiencies were observed. She was diagnosed with painless thyroiditis and secondary adrenal insufficiency based on the positive thyroglobulin antibody, negative TSH receptor antibody, decreased Doppler flow in thyroid ultrasonography, low adrenocorticotrophic hormone (ACTH), and low response of ACTH and cortisol to corticotropin-releasing hormone loading test. MRI revealed no abnormalities. We report a case of thyrotoxicosis and secondary adrenal insufficiency five months after the first administration of nivolumab and ipilimumab. Careful follow-up and early detection of endocrine disorders are critical in patients treated with a combination of ICIs.
PubMed: 38910605
DOI: 10.7759/cureus.60850 -
Endocrine Journal Jun 2024Although growth hormone (GH) and prolactin (PRL) are usually recognized as pituitary hormones, their expression is not restricted to the adenohypophysis and can also be...
Although growth hormone (GH) and prolactin (PRL) are usually recognized as pituitary hormones, their expression is not restricted to the adenohypophysis and can also be found in extra-pituitary tissues including placenta. Furthermore, GH, PRL, and their receptors structurally belong to the cytokine family of proteins, and indeed they have remarkable pleiotropic effects. In this review, we analyzed the biological roles of GH/PRL from an evolutionary perspective. We have recognized that the biological significance of GH/PRL can be summarized as follows: cytokines (metabokines) that regulate the shift of nutrients and even of whole bodies to live in the most appropriate environment(s) for conducting growth and reproduction. In this sense, the common keyword of the two metabokines is "shift" for environmental adaptation. Considering that these metabokines flexibly changed their biological roles, GH/PRL may have played important roles during vertebrate evolution.
PubMed: 38910132
DOI: 10.1507/endocrj.EJ24-0118 -
The Journal of Maternal-fetal &... Dec 2024The current study aims to evaluate the correlation between oxytocin augmentation and postpartum hemorrhage. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The current study aims to evaluate the correlation between oxytocin augmentation and postpartum hemorrhage.
METHOD
PubMed, Web of Science, and Scopus has been searched for studies assessing the correlation between oxytocin augmentation and postpartum hemorrhage up to January 24, 2024. The search strategy included relevant keywords related to PPH and oxytocin augmentation. The risk of bias assessment was conducted by two reviewers using the Newcastle-Ottawa Scale (NOS). To pool the effects sized of included studies odds ratios (OR) of interest outcome with their 95% confidence interval (CI) were used.
RESULTS
Eight studies were included in this meta-analysis. The pooled analysis of the included studies showed a statistically significant association between oxytocin augmentation and increased odds of PPH (pooled odds ratio [OR] = 1.27, 95% confidence interval [CI]: 1.05-1.53; I2 = 84.94%; = 0.01). Publication bias was assessed using funnel plots, which appeared relatively asymmetrical, indicating significant publication bias. Galbraith plot and trim and fill plot were used for publication bias. Sensitivity analyses were performed by leave one out method.
CONCLUSION
This meta-analysis suggests that using oxytocin for labor augmentation is linked to a significant increase in the risk of PPH. It highlights the need for careful monitoring and consideration when using oxytocin, especially in low and middle-income countries where guidelines and supervision are crucial.
Topics: Humans; Oxytocin; Female; Postpartum Hemorrhage; Pregnancy; Oxytocics
PubMed: 38910114
DOI: 10.1080/14767058.2024.2369210