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Genes Jun 2024is a LIM-homeodomain transcription factor that affects body size in mammals by regulating the secretion of pituitary hormones. Akita, Shiba Inu, and Mame Shiba Inu dogs...
is a LIM-homeodomain transcription factor that affects body size in mammals by regulating the secretion of pituitary hormones. Akita, Shiba Inu, and Mame Shiba Inu dogs are Japanese native dog breeds that have different body sizes. To determine whether plays a role in the differing body sizes of these three dog breeds, we sequenced the gene in the three breeds, which led to the identification of an SNP in codon 280 (S280N) associated with body size. The allele frequency at this SNP differed significantly between the large Akita and the two kinds of smaller Shiba dogs. To validate the function of this SNP on body size, we introduced this change into the gene of mice. Homozygous mutant mice (S279N) were found to have significantly increased body lengths and weights compared to heterozygous mutant (S279N) and wild-type (S279N) mice several weeks after weaning. These results demonstrate that a nonsynonymous substitution in plays an important role in regulating body size in mammals.
Topics: Animals; LIM-Homeodomain Proteins; Transcription Factors; Mice; Body Size; Dogs; Polymorphism, Single Nucleotide; Gene Frequency; Male; Female
PubMed: 38927675
DOI: 10.3390/genes15060739 -
Biomedicines Jun 2024Research has identified fetal risk factors for adult diseases, forming the basis for the Developmental Origins of Health and Disease (DOHaD) hypothesis. DOHaD suggests... (Review)
Review
A Review of Fetal Development in Pregnancies with Maternal Type 2 Diabetes Mellitus (T2DM)-Associated Hypothalamic-Pituitary-Adrenal (HPA) Axis Dysregulation: Possible Links to Pregestational Prediabetes.
Research has identified fetal risk factors for adult diseases, forming the basis for the Developmental Origins of Health and Disease (DOHaD) hypothesis. DOHaD suggests that maternal insults during pregnancy cause structural and functional changes in fetal organs, increasing the risk of chronic diseases like type 2 diabetes mellitus (T2DM) in adulthood. It is proposed that altered maternal physiology, such as increased glucocorticoid (GC) levels associated with a dysregulated hypothalamic-pituitary-adrenal (HPA) axis in maternal stress and T2DM during pregnancy, exposes the fetus to excess GC. Prenatal glucocorticoid exposure reduces fetal growth and programs the fetal HPA axis, permanently altering its activity into adulthood. This programmed HPA axis is linked to increased risks of hypertension, cardiovascular diseases, and mental disorders in adulthood. With the global rise in T2DM, particularly among young adults of reproductive age, it is crucial to prevent its onset. T2DM is often preceded by a prediabetic state, a condition that does not show any symptoms, causing many to unknowingly progress to T2DM. Studying prediabetes is essential, as it is a reversible stage that may help prevent T2DM-related pregnancy complications. The existing literature focuses on HPA axis dysregulation in T2DM pregnancies and its link to fetal programming. However, the effects of prediabetes on HPA axis function, specifically glucocorticoid in pregnancy and fetal outcomes, are not well understood. This review consolidates research on T2DM during pregnancy, its impact on fetal programming via the HPA axis, and possible links with pregestational prediabetes.
PubMed: 38927579
DOI: 10.3390/biomedicines12061372 -
Biomedicines Jun 2024Hypothyroidism is a frequently diagnosed endocrine disorder. Common signs and symptoms include fatigue, cold intolerance, hoarseness, dry skin, constipation, a slow...
Hypothyroidism is a frequently diagnosed endocrine disorder. Common signs and symptoms include fatigue, cold intolerance, hoarseness, dry skin, constipation, a slow relaxation phase of deep tendon reflexes, and bradycardia. However, some patients may exhibit atypical signs and symptoms, which can result in diagnostic confusion. Pituitary hyperplasia resulting from longstanding primary hypothyroidism was first described by Niepce in 1851. It is usually asymptomatic, but sometimes, in addition to symptoms of overt hypothyroidism, patients may complain of headaches, hypopituitarism, visual field impairment, and hyperprolactinemia. Furthermore, on imaging, pituitary hyperplasia can be mistaken for a pituitary adenoma. Distinguishing between the two is crucial, as their management differs; the former often responds to thyroid hormone replacement therapy, while the latter might need treatment with surgery and/or radiotherapy. Here we describe a patient who developed pituitary hyperplasia in the setting of longstanding uncompensated primary hypothyroidism due to a lack of compliance with levothyroxine replacement therapy. We also review the clinical, laboratory, and radiologic findings of the case reports available in the literature up to now in order to improve the knowledge and the care of the disease.
PubMed: 38927575
DOI: 10.3390/biomedicines12061368 -
Scientific Reports Jun 2024Previously, we demonstrated the expression of visfatin in porcine reproductive tissues and its effect on pituitary endocrinology. The objective of this study was to...
Previously, we demonstrated the expression of visfatin in porcine reproductive tissues and its effect on pituitary endocrinology. The objective of this study was to examine the visfatin effect on the secretion of steroid (P, E) and prostaglandin (PGE, PGF), the mRNA and protein abundance of steroidogenic markers (STAR, CYP11A1, HSD3B, CYP19A1), prostaglandin receptors (PTGER2, PTGFR), insulin receptor (INSR), and activity of kinases (MAPK/ERK1/2, AKT, AMPK) in the porcine corpus luteum. We noted that the visfatin effect strongly depends on the phase of the estrous cycle: on days 2-3 and 14-16 it reduced P, while on days 10-12 it stimulated P. Visfatin increased secretion of E on days 2-3, PGE on days 2-3 and 10-12, reduced PGF release on days 14-16, as well as stimulated the expression of steroidogenic markers on days 10-12 of the estrous cycle. Moreover, visfatin elevated PTGER mRNA expression and decreased its protein level, while we noted the opposite changes for PTGFR. Additionally, visfatin activated ERK1/2, AKT, and AMPK, while reduced INSR phosphorylation. Interestingly, after inhibition of INSR and signalling pathways visfatin action was abolished. These findings suggest a regulatory role of visfatin in the porcine corpus luteum.
Topics: Animals; Corpus Luteum; Female; Swine; Nicotinamide Phosphoribosyltransferase; Estrous Cycle; Receptor, Insulin; Progesterone; Receptors, Prostaglandin; Dinoprost
PubMed: 38926439
DOI: 10.1038/s41598-024-65102-4 -
NPJ Vaccines Jun 2024Following administration of the SARS-CoV-2 vaccine, many women worldwide reported short-term menstrual irregularities. Although menstrual bleeding, "the fifth vital...
Following administration of the SARS-CoV-2 vaccine, many women worldwide reported short-term menstrual irregularities. Although menstrual bleeding, "the fifth vital sign", is experienced by more than 300 million people on any given day worldwide, these changes were only partially studied. Irregular periods are important well beyond fertility and the discomfort they impose; they are associated with the risk of cardiovascular morbidity, chronic diseases, and premature mortality. Pre-clinical examination of the vaccine polymeric envelope indicates its accumulation in the ovaries. The somatic endocrine cells of the ovarian follicle - the granulosa cells (GCs)-participate in the strict hypothalamic-pituitary-ovarian (HPO) feedback loop that governs the menstrual cycle via endocrine and paracrine regulators, as AMH and Inhibins. We aimed to unravel the direct effect of the COVID-19 vaccine on GCs and link their post-vaccine activity to changes in menstrual patterns. Human primary GCs exposed in-vitro to the Pfizer COVID-19 vaccine BNT162b2, demonstrated no change in their viability but altered mRNA transcripts, specifically of the regulatory key factors: InhibinB was upregulated, whereas AMH was downregulated. We further examined pre- and post-vaccination blood samples from individual women and found a 2-3 folds change in the post-vaccination FSH/InhibinB protein level ratio, compared to their pre-vaccination values. This altered expression of InhibinB could significantly impact the HPO axis in vaccinated women and may ultimately influence the endometrium cyclicity, manifested clinically by the commonly reported changes in menstrual bleeding patterns.
PubMed: 38926432
DOI: 10.1038/s41541-024-00911-2 -
Endokrynologia Polska Jun 2024Not required in Clinical Vignettes.
Not required in Clinical Vignettes.
PubMed: 38923901
DOI: 10.5603/ep.99199 -
Metabolites Jun 2024Relative energy deficiency in sport (RED-S) is a condition that arises from persistent low energy availability (LEA), which affects the hypothalamic-pituitary axis and...
Development of an LC-HRMS/MS Method for Quantifying Steroids and Thyroid Hormones in Capillary Blood: A Potential Tool for Assessing Relative Energy Deficiency in Sport (RED-S).
Relative energy deficiency in sport (RED-S) is a condition that arises from persistent low energy availability (LEA), which affects the hypothalamic-pituitary axis and results in alterations of several hormones in both male and female athletes. As frequent blood hormone status determinations using venipuncture are rare in sports practice, microsampling offers promising possibilities for preventing and assessing RED-S. Therefore, this study aimed at developing a liquid chromatography-high-resolution tandem mass spectrometry (LC-HRMS/MS) method for quantifying relevant steroids and thyroid hormones in 30 μL of capillary blood obtained using Mitra devices with volumetric absorptive microsampling technology (VAMS). The results of the study showed that all validation criteria were met, including a storage stability of more than 28 days in a frozen state (-18 °C) and 14 days at room temperature (20 °C). The validated assay provided precise (<12%) and accurate (<13%) results for all the target analytes. Furthermore, as a proof of concept, autonomously collected VAMS samples from 50 female and male, healthy, active adults were analyzed. The sensitivity of all analytes was adequate to quantify the decreased hormone concentrations in the RED-S state, as all authentic samples could be measured accordingly. These findings suggest that self-collected VAMS samples offer a practical opportunity for regular hormone measurements in athletes and can be used for early RED-S assessment and progress monitoring during RED-S recovery.
PubMed: 38921463
DOI: 10.3390/metabo14060328 -
Current Issues in Molecular Biology May 2024Sexual maturation of Atlantic salmon males is marked by dramatic endocrine changes and rapid growth of the testes, resulting in an increase in the gonad somatic index...
Sexual maturation of Atlantic salmon males is marked by dramatic endocrine changes and rapid growth of the testes, resulting in an increase in the gonad somatic index (GSI). We examined the association of gonadal growth with serum sex steroids, as well as pituitary and testicular gene expression levels, which were assessed with a DNA oligonucleotide microarray. The testes transcriptome was stable in males with a GSI < 0.08% despite the large difference between the smallest and the largest gonads. Fish with a GSI ≥ 0.23% had 7-17 times higher serum levels of five male steroids and a 2-fold increase in progesterone, without a change in cortisol and related steroids. The pituitary transcriptome showed an upregulation of the hormone-coding genes that control reproduction and behavior, and structural rearrangement was indicated by the genes involved in synaptic transmission and the differentiation of neurons. The observed changes in the abundance of testicular transcripts were caused by the regulation of transcription and/or disproportional growth, with a greater increase in the germinative compartment. As these factors could not be separated, the transcriptome results are presented as higher or lower specific activities (HSA and LSA). LSA was observed in 4268 genes, including many genes involved in various immune responses and developmental processes. LSA also included genes with roles in female reproduction, germinal cell maintenance and gonad development, responses to endocrine and neural regulation, and the biosynthesis of sex steroids. Two functional groups prevailed among HSA: structure and activity of the cilia (95 genes) and meiosis (34 genes). The puberty of A. salmon testis is marked by the predominance of spermatogenesis, which displaces other processes; masculinization; and the weakening of external regulation. Results confirmed the known roles of many genes involved in reproduction and pointed to uncharacterized genes that deserve attention as possible regulators of sexual maturation.
PubMed: 38920991
DOI: 10.3390/cimb46060319 -
JCEM Case Reports Jun 2024Chiari 1 malformation (CM1) is a rare finding that has been described with growth hormone (GH)-secreting pituitary adenomas and with an endothelial PAS domain protein 1...
Chiari 1 malformation (CM1) is a rare finding that has been described with growth hormone (GH)-secreting pituitary adenomas and with an endothelial PAS domain protein 1 gain-of-function mutation syndrome. We describe the first reported case of a patient diagnosed with CM1 and nonfunctioning pituitary and adrenal incidentalomas. Our case describes a 45-year-old female who was found to have cerebellar tonsillar ectopia consistent with CM1, a pituitary tumor, and bilateral adrenal incidentalomas. She was diagnosed after presenting with 2 weeks of upper extremity weakness and paresthesia. A comprehensive endocrine workup including insulin like growth factor (IGF-1) was normal. She underwent posterior fossa decompression without complication. Pituitary adenectomy was not pursued as there was no evidence of compression of the chiasm or the surrounding structures. In previous case reports it has been proposed that GH-secreting adenomas contribute to CM1 by causing hypertrophy of soft tissue structures in the skull base, overcrowding the posterior fossa. Given that our patient had normal IGF-1 levels, there could be a different underlying mechanism that contributed to the concomitant occurrence of CM1 with the pituitary and adrenal tumors.
PubMed: 38919912
DOI: 10.1210/jcemcr/luae113 -
Frontiers in Human Neuroscience 2024Brain cancer is a frequently occurring disease around the globe and mostly developed due to the presence of tumors in/around the brain. Generally, the prevalence and...
INTRODUCTION
Brain cancer is a frequently occurring disease around the globe and mostly developed due to the presence of tumors in/around the brain. Generally, the prevalence and incidence of brain cancer are much lower than that of other cancer types (breast, skin, lung, etc.). However, brain cancers are associated with high mortality rates, especially in adults, due to the false identification of tumor types, and delay in the diagnosis. Therefore, the minimization of false detection of brain tumor types and early diagnosis plays a crucial role in the improvement of patient survival rate. To achieve this, many researchers have recently developed deep learning (DL)-based approaches since they showed a remarkable performance, particularly in the classification task.
METHODS
This article proposes a novel DL architecture named BrainCDNet. This model was made by concatenating the pooling layers and dealing with the overfitting issues by initializing the weights into layers using 'He Normal' initialization along with the batch norm and global average pooling (GAP). Initially, we sharpen the input images using a Nimble filter, which results in maintaining the edges and fine details. After that, we employed the suggested BrainCDNet for the extraction of relevant features and classification. In this work, two different forms of magnetic resonance imaging (MRI) databases such as binary (healthy vs. pathological) and multiclass (glioma vs. meningioma vs. pituitary) are utilized to perform all these experiments.
RESULTS AND DISCUSSION
Empirical evidence suggests that the presented model attained a significant accuracy on both datasets compared to the state-of-the-art approaches, with 99.45% (binary) and 96.78% (multiclass), respectively. Hence, the proposed model can be used as a decision-supportive tool for radiologists during the diagnosis of brain cancer patients.
PubMed: 38919881
DOI: 10.3389/fnhum.2024.1405586