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Biomedicine & Pharmacotherapy =... May 2024Depression ranks as the fourth most prevalent global disease, with suicide incidents occurring at a younger age. Sulpiride (SUL), an atypical antidepressant drug acting...
Depression ranks as the fourth most prevalent global disease, with suicide incidents occurring at a younger age. Sulpiride (SUL), an atypical antidepressant drug acting as a dopamine D2 receptor antagonist and possessing anti-inflammatory properties, exhibits limited ability to penetrate the blood brain barrier (BBB). This weak penetration hampers its inhibitory effect on prolactin release in the pituitary gland, consequently leading to hyperprolactinemia. In order to enhance the central nervous system efficacy of sulpiride and reduce serum prolactin levels, we covalently linked sulpiride to VPALR derived from the nuclear DNA repair protein ku70. In vivo study on depressive mice using intraperitoneal injection of VPALR-SUL demonstrated a significant increase in struggle time and total distance compared to those treated with only sulpiride while also reducing serum prolactin concentration. The pharmacokinetic study results showed that VPALR-SUL prolonged half-life and increased bioavailability. In conclusion, VPALR-SUL exhibited potential for enhancing sulpiride transport across the BBB, augmenting its antidepressant effects, and reducing serum prolactin levels. This study laid a foundation for improving sulpiride delivery and developing novel antidepressants.
Topics: Animals; Prolactin; Sulpiride; Antidepressive Agents; Mice; Male; Cell-Penetrating Peptides; Depression; Blood-Brain Barrier; Biological Availability
PubMed: 38642503
DOI: 10.1016/j.biopha.2024.116610 -
PloS One 2024Obesity leads to insulin resistance (IR) and type 2 diabetes. In humans, low levels of the hormone prolactin (PRL) correlate with IR, adipose tissue (AT) dysfunction,...
Obesity leads to insulin resistance (IR) and type 2 diabetes. In humans, low levels of the hormone prolactin (PRL) correlate with IR, adipose tissue (AT) dysfunction, and increased prevalence of T2D. In obese rats, PRL treatment promotes insulin sensitivity and reduces visceral AT adipocyte hypertrophy. Here, we tested whether elevating PRL levels with the prokinetic and antipsychotic drug sulpiride, an antagonist of dopamine D2 receptors, improves metabolism in high fat diet (HFD)-induced obese male mice. Sulpiride treatment (30 days) reduced hyperglycemia, IR, and the serum and pancreatic levels of triglycerides in obese mice, reduced visceral and subcutaneous AT adipocyte hypertrophy, normalized markers of visceral AT function (PRL receptor, Glut4, insulin receptor and Hif-1α), and increased glycogen stores in skeletal muscle. However, the effects of sulpiride reducing hyperglycemia were also observed in obese prolactin receptor null mice. We conclude that sulpiride reduces obesity-induced hyperglycemia by mechanisms that are independent of prolactin/prolactin receptor activity. These findings support the therapeutic potential of sulpiride against metabolic dysfunction in obesity.
Topics: Humans; Mice; Male; Rats; Animals; Insulin Resistance; Mice, Obese; Dopamine D2 Receptor Antagonists; Prolactin; Receptors, Prolactin; Diabetes Mellitus, Type 2; Sulpiride; Obesity; Diet, High-Fat; Hyperglycemia; Hypertrophy; Insulin
PubMed: 38635745
DOI: 10.1371/journal.pone.0301496 -
Pharmacology, Biochemistry, and Behavior Jun 2024Pituitary lactotrophs are under tonic dopaminergic inhibitory control and bromocriptine treatment blocks prolactin secretion.
BACKGROUND
Pituitary lactotrophs are under tonic dopaminergic inhibitory control and bromocriptine treatment blocks prolactin secretion.
METHODS
Sleep and local field potential were addressed for 72 h after bromocriptine treatments applied during the different stages of the estrus cycle and for 24 h in the early- and middle postpartum period characterized by spontaneously different dynamics of prolactin release in female rats.
RESULTS
Sleep changes showed strong dependency on the estrus cycle phase of the drug application. Strongest increase of wakefulness and reduction of slow wave sleep- and rapid eye movements sleep appeared during diestrus-proestrus and middle postpartum treatments. Stronger sleep-wake effects appeared in the dark phase in case of the estrus cycle treatments, but in the light phase in postpartum treatments. Slow wave sleep and REM sleep loss in case of estrus cycle treatments was not compensated at all and sleep loss seen in the first day post-injection was gained further later. In opposition, slow wave sleep loss in the light phase after bromocriptine injections showed compensation in the postpartum period treatments. Bromocriptine treatments resulted in a depression of local field potential delta power during slow wave sleep while an enhancement in beta and gamma power during wakefulness regardless of the treatment timing.
CONCLUSIONS
These results can be explained by the interplay of dopamine D2 receptor agonism, lack of prolactin release and the spontaneous homeostatic sleep drive being altered in the different stages of the estrus cycle and the postpartum period.
Topics: Animals; Bromocriptine; Female; Postpartum Period; Rats; Receptors, Dopamine D2; Dopamine Agonists; Estrous Cycle; Rats, Wistar; Sleep; Wakefulness; Prolactin
PubMed: 38537873
DOI: 10.1016/j.pbb.2024.173754 -
Open Forum Infectious Diseases Mar 2024Astroviral infections commonly cause acute nonbacterial gastroenteritis in children globally. However, these infections often go undiagnosed outside of research...
BACKGROUND
Astroviral infections commonly cause acute nonbacterial gastroenteritis in children globally. However, these infections often go undiagnosed outside of research settings. There is no treatment available for astrovirus, and Astroviridae strain diversity presents a challenge to potential vaccine development.
METHODS
To address our hypothesis that host genetic risk factors are associated with astrovirus disease susceptibility, we performed a genome-wide association study of astrovirus infection in the first year of life from children enrolled in 2 Bangladeshi birth cohorts.
RESULTS
We identified a novel region on chromosome 1 near the loricrin gene () associated with astrovirus diarrheal infection (rs75437404; meta-analysis = 8.82 × 10; A allele odds ratio, 2.71) and on chromosome 10 near the prolactin releasing hormone receptor gene () (rs75935441; meta-analysis = 1.33 × 10; C allele odds ratio, 4.17). The prolactin-releasing peptide has been shown to influence feeding patterns and energy balance in mice. In addition, several single-nucleotide polymorphisms in the chromosome 1 locus have previously been associated with expression of innate immune system genes and .
CONCLUSIONS
This study identified 2 significant host genetic regions that may influence astrovirus diarrhea susceptibility and should be considered in further studies.
PubMed: 38524222
DOI: 10.1093/ofid/ofae045 -
Frontiers in Endocrinology 2024Ectopic thyroid-stimulating hormone (TSH)-secreting tumors are extremely rare, with only 15 reported cases in the literature. Herein, we described a 60-year-old female... (Review)
Review
Ectopic thyroid-stimulating hormone (TSH)-secreting tumors are extremely rare, with only 15 reported cases in the literature. Herein, we described a 60-year-old female patient with thyrotoxicosis and elevated or unsuppressed levels of TSH. Family history and laboratory and genetic tests did not support a diagnosis of resistance to thyroid hormone (RTH). Given the unsuppressed TSH, TSH-secreting tumor was suspected, and magnetic resonance imaging (MRI) of the pituitary gland was performed. Surprisingly, the MRI scans revealed a nodule in the nasopharynx rather than a pituitary tumor in the sella region. Further evaluation using Gallium-68 DOTATATE positron emission tomography/computed tomography (Ga-DOTATATE PET/CT) demonstrated increased DOTATATE uptake in the nasopharyngeal nodule. Additionally, an octreotide suppression test (OST) revealed an obvious reduction in TSH levels, further supporting the suspicion of the nasopharyngeal mass as the cause of inappropriate TSH secretion. To prepare for surgery, the patient received preoperative administration of octreotide, resulting in the normalization of TSH and thyroid hormone levels. The patient subsequently underwent successful surgical removal of the nasopharyngeal mass. Following the procedure, the patient experienced complete resolution of hyperthyroidism symptoms, with TSH declined and thyroid hormone levels returned to normal. Histochemistry analysis of the tumor revealed positive staining for TSH, growth hormone (GH), prolactin (PRL), luteinizing hormone (LH), and somatostatin receptor 2 (SSTR2). We discussed differential diagnosis of hyperthyroidism due to inappropriate TSH secretion, with a particular emphasis on the importance of Ga-DOTATATE PET/CT in combination with OST for identifying ectopic pituitary tumors.
Topics: Female; Humans; Middle Aged; Adenoma; Gallium Radioisotopes; Hyperthyroidism; Octreotide; Pituitary Neoplasms; Positron Emission Tomography Computed Tomography; Thyroid Hormones; Thyroid Neoplasms; Thyrotropin
PubMed: 38516415
DOI: 10.3389/fendo.2024.1301260 -
BMC Genomics Mar 2024Muscle growth post-birth relies on muscle fiber number and size. Myofibre number, metabolic and contractile capacities are established pre-birth during prenatal...
BACKGROUND
Muscle growth post-birth relies on muscle fiber number and size. Myofibre number, metabolic and contractile capacities are established pre-birth during prenatal myogenesis. The aim of this study was to identify genes involved in skeletal muscle development in cattle, sheep, and pigs - livestock.
RESULTS
The cattle analysis showed significant differences in 5043 genes during the 135-280 dpc period. In sheep, 444 genes differed significantly during the 70-120 dpc period. Pigs had 905 significantly different genes for the 63-91 dpc period.The biological processes and KEGG pathway enrichment results in each species individually indicated that DEGs in cattle were significantly enriched in regulation of cell proliferation, cell division, focal adhesion, ECM-receptor interaction, and signaling pathways (PI3K-Akt, PPAR, MAPK, AMPK, Ras, Rap1); in sheep - positive regulation of fibroblast proliferation, negative regulation of endothelial cell proliferation, focal adhesion, ECM-receptor interaction, insulin resistance, and signaling pathways (PI3K-Akt, HIF-1, prolactin, Rap1, PPAR); in pigs - regulation of striated muscle tissue development, collagen fibril organization, positive regulation of insulin secretion, focal adhesion, ECM-receptor interaction, and signaling pathways (PPAR, FoxO, HIF-1, AMPK). Among the DEGs common for studied animal species, 45 common genes were identified. Based on these, a protein-protein interaction network was created and three significant modules critical for skeletal muscle myogenesis were found, with the most significant module A containing four recognized hub genes - EGFR, VEGFA, CDH1, and CAV1. Using the miRWALK and TF2DNA databases, miRNAs (bta-miR-2374 and bta-miR-744) and transcription factors (CEBPB, KLF15, RELA, ZNF143, ZBTB48, and REST) associated with hub genes were detected. Analysis of GO term and KEGG pathways showed that such processes are related to myogenesis and associated with module A: positive regulation of MAP kinase activity, vascular endothelial growth factor receptor, insulin-like growth factor binding, focal adhesion, and signaling pathways (PI3K-Akt, HIF-1, Rap1, Ras, MAPK).
CONCLUSIONS
The identified genes, common to the prenatal developmental period of skeletal muscle in livestock, are critical for later muscle development, including its growth by hypertrophy. They regulate valuable economic characteristics. Enhancing and breeding animals according to the recognized genes seems essential for breeders to achieve superior gains in high-quality muscle mass.
Topics: Swine; Animals; Cattle; Sheep; Gene Expression Profiling; Livestock; Proto-Oncogene Proteins c-akt; Phosphatidylinositol 3-Kinases; AMP-Activated Protein Kinases; Peroxisome Proliferator-Activated Receptors; Vascular Endothelial Growth Factor A; Muscle, Skeletal; MicroRNAs; Muscle Development
PubMed: 38504177
DOI: 10.1186/s12864-024-10196-3 -
Narra J Dec 2023Congenital hypothyroidism is the deficiency of thyroid hormone in infants and hyperprolactinemia is frequently observed. Previously reported cases typically involve...
Congenital hypothyroidism is the deficiency of thyroid hormone in infants and hyperprolactinemia is frequently observed. Previously reported cases typically involve intellectual disability, highlighting this particular unique case report to the first reported patient demonstrating normal intellectual ability despite experiencing growth and gonad dysfunction. This study aims to present a case and review medical hypotheses related to the patient's condition. A 19-year-old female presented with a chief complaint of irregular menstruation for up to 40 days or not occurring at all. The patient experienced the first menstruation at the age of 16 years old. The patient's height was 133 cm, body weight 40 kg, and body mass index 22.61 kg/m2; other family members were normal. Physical examination showed no abnormalities, and laboratory examination showed suppressed serum free T4 (FT4) level (6.41 pmol/L), elevated thyroid stimulating hormone (TSH) level (333.700 µIU/mL), and elevated prolactin hormone level (32.03 ng/mL). Ultrasound of the thyroid gland found hypoplasia of the left and right thyroid glands. The patient was a college student enrolled in a public national university and had never complained about academic performance throughout the patient's education. The patient was diagnosed with congenital hypothyroidism and hyperprolactinemia. The patient was administered up to 100 µg daily of oral levothyroxine, which improved the patient's menstrual cycles. The patient's delayed diagnosis may be attributed to central congenital hypothyroidism being underdiagnosed. We hypothesized that thyroid-releasing hormone receptor () gene mutation might contribute to the underlying cause of hyperprolactinemia and normal intellectual ability of the patient. Further study on the significance of gene mutations in congenital hypothyroidism is required to improve diagnosis and treatment.
PubMed: 38455622
DOI: 10.52225/narra.v3i3.205 -
Heliyon Mar 2024Fluctuations in olfactory sensitivity are widely known to occur during pregnancy and may be responsible for hyperemesis gravidarum. These changes are thought to be...
Fluctuations in olfactory sensitivity are widely known to occur during pregnancy and may be responsible for hyperemesis gravidarum. These changes are thought to be caused by structural and functional alterations in neurons in response to marked changes of the hormonal milieu. In this study, we examined changes in neurons in the olfactory cortex during pregnancy and after delivery in rats. Dendritic spine densities were measured in the piriform cortex (PIR) and posterolateral cortical amygdala (COApl), which are involved in olfaction. The results showed increased numbers of dendritic spines in the PIR in mid-pregnancy and in the COApl during early and late pregnancy, but not in the motor area of the cerebral cortex, indicating a correlation with changes in olfactory sensitivity during pregnancy. Immunohistochemical analysis of expression of ovarian hormone receptors in these brain regions revealed a decrease in the number of estrogen receptor α-positive cells during pregnancy in the PIR and during pregnancy and the postpartum period in the COApl. Regarding pregnancy-related peptide hormones, oxytocin receptors were expressed in the PIR and COApl, while prolactin receptors were not found in these regions. Accordingly, oxytocin-containing neurites were distributed in both regions. These results suggest that the balance of these hormonal signals has an effect on olfactory sensitivity in pregnant females.
PubMed: 38444488
DOI: 10.1016/j.heliyon.2024.e26780