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International Journal of Molecular... Sep 2023Breast cancer remains the most frequently diagnosed cancer in women worldwide. Tumors that express hormone receptors account for 75% of all cases. Understanding... (Review)
Review
Breast cancer remains the most frequently diagnosed cancer in women worldwide. Tumors that express hormone receptors account for 75% of all cases. Understanding alternative signaling cascades is important for finding new therapeutic targets for hormone receptor-positive breast cancer patients. JAK-STAT signaling is commonly activated in hormone receptor-positive breast tumors, inducing inflammation, proliferation, migration, and treatment resistance in cancer cells. In hormone receptor-positive breast cancer, the JAK-STAT cascade is stimulated by hormones and cytokines, such as prolactin and IL-6. In normal cells, JAK-STAT is inhibited by the action of the adaptor protein, LNK. However, the role of LNK in breast tumors is not fully understood. This review compiles published reports on the expression and activation of the JAK-STAT pathway by IL-6 and prolactin and potential inhibition of the cascade by LNK in hormone receptor-positive breast cancer. Additionally, it includes analyses of available datasets to determine the level of expression of LNK and various members of the JAK-STAT family for the purpose of establishing associations between expression and clinical outcomes. Together, experimental evidence and in silico studies provide a better understanding of the potential implications of the JAK-STAT-LNK loop in hormone receptor-positive breast cancer progression.
Topics: Humans; Female; Signal Transduction; Janus Kinases; Breast Neoplasms; Prolactin; Interleukin-6; STAT Transcription Factors
PubMed: 37834225
DOI: 10.3390/ijms241914777 -
Postepy Dermatologii I Alergologii Dec 2023is one of the most common dermatological diseases. Hormonal imbalance affects the skin condition and results in the formation of lesions.
INTRODUCTION
is one of the most common dermatological diseases. Hormonal imbalance affects the skin condition and results in the formation of lesions.
AIM
To evaluate serum levels of testosterone, prolactin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), triglycerides (TG), and high-density lipoprotein (HDL) in patients with and compare them to healthy population.
MATERIAL AND METHODS
Forty-one patients with and 47 age- and body mass index (BMI)-matched controls were enrolled in the study.
RESULTS
The mean ± SD testosterone serum level in the study group was 0.45 ±1.03 ng/ml in females and 4.24 ±0.68 in males and in the control group 0.73 ±2.03 ng/ml and 5.3 ±1.3 ng/ml in females and males, respectively. The prolactin serum level was 16.73 ±8.02 ng/ml in the study group and in the control group 13.74 ±8.71 ng/ml ( = 0.011). The FSH serum level was 12.17 ±16.93 mIU/ml and 6.2 ±7.3 mIU/ml in the study and control groups, respectively ( = 0.0001), whereas LH serum levels were 18.44 ±19.71 mIU/ml and 11.26 ±8 mIU/ml, respectively ( = 0.2659). The HDL serum level was 65.63 ±15.67 mg/dl in the study group and 61.53 ±15.89 mg/dl in the control group ( = 0.219), and TG levels were 175.29 ±82.15 mg/dl and 87.32 ±30.64 mg/dl, respectively ( < 0.00001).
CONCLUSIONS
Our study demonstrates, that hormonal and lipid imbalance could be linked to formation. Evaluation of hormonal and lipid abnormalities could help in treatment decisions and could affect the occurrence of complications and the course of acne.
PubMed: 38282870
DOI: 10.5114/ada.2023.133457 -
Frontiers in Endocrinology 2023To investigate the prevalence of low blood testosterone level (LTL) and its determinant factors among active male acromegaly patients, as well as the effect of surgery...
PURPOSE
To investigate the prevalence of low blood testosterone level (LTL) and its determinant factors among active male acromegaly patients, as well as the effect of surgery on LTL in male acromegaly patients.
METHODS
A retrospective, single-center study focused on 252 male acromegaly patients aged 18 years-60 years diagnosed in the Peking Union Medical College Hospital from January 2015 to December 2018 was carried out. The measurements of preoperative and postoperative testosterone levels, serum growth hormone (GH), insulin-like growth factor 1 (IGF-1), and other clinical data were analyzed.
RESULTS
Forty per cent of subjects included were diagnosed with LTL pre surgery. Patients were divided into normal testosterone level (NTL) and LTL groups based on their testosterone level. There were significant differences ( < 0.01) between groups in the presence of macroadenomas, invasion of the cavernous sinus, compression of the optic chiasm, and serum GH and prolactin levels pre surgery. Invasion of the cavernous sinus [odds ratio (OR) = 4.299; = 0.000] and serum prolactin level (OR = 1.023, = 0.001) were independent predictors of LTLs in male patients before surgical intervention. A total of 67.9% of LTL patients recovered during the follow-up, with a new-onset rate of 3.4%. Body mass index, invasion of the cavernous sinus, GH, IGF-1, and prolactin levels, the presence of a prolactin-secreting tumor, and recovery from acromegaly were significantly different ( < 0.05) in the NTL group and in the LTL group during the follow-up. The presence of a prolactin-secreting tumor (OR = 0.224; = 0.001) and recovery from acromegaly (OR = 0.168; = 0.006) were independent predictors of LTLs in male acromegaly patients during the follow-up.
CONCLUSION
The invasiveness of tumor and levels of blood prolactin are independent factors for LTLs before surgery, whereas GH and IGF-1 levels are not. Most male patients can recover from LTL after tumor restriction surgery: those who recover from acromegaly have a better chance of recovering from LTL.
Topics: Humans; Male; Acromegaly; Insulin-Like Growth Factor I; Prospective Studies; Prolactin; Retrospective Studies; Pituitary Neoplasms; Testosterone
PubMed: 37886642
DOI: 10.3389/fendo.2023.1259529 -
Cancers Feb 2024Several subtypes of pituitary neuroendocrine tumors (PitNETs), such as acromegaly and Cushing's disease, can result in hypertension. However, whether prolactinoma is...
Several subtypes of pituitary neuroendocrine tumors (PitNETs), such as acromegaly and Cushing's disease, can result in hypertension. However, whether prolactinoma is associated with this complication remains unknown. Moreover, the effect of treatment with surgery or drugs on blood pressure (BP) is unknown. Herein, a retrospective study reviewed 162 patients with prolactinoma who underwent transsphenoidal surgery between January 2005 and December 2022. BP measurements were performed 1 day before and 5 days after surgery. Accordingly, patients' medical characteristics were recorded. In addition, in situ rat and xenograft nude-mice prolactinoma models have been used to mimic prolactinoma. In vivo BP and serum prolactin (PRL) levels were measured after cabergoline (CAB) administration in both rats and mice. Our data suggest that surgery can effectively decrease BP in prolactinoma patients with or without hypertension. The BP-lowering effect was significantly associated with several variables, including age, sex, disease duration, tumor size, invasion, dopamine agonists (DAs)-resistance, recurrence, and preoperative PRL levels. Moreover, in situ and xenograft prolactinomas induced BP elevation, which was alleviated by CAB treatment without and with a statistical difference in rats and mice, respectively. Thus, surgery or CAB can decrease BP in prolactinoma, indicating that pre- and postoperative BP management becomes essential.
PubMed: 38398117
DOI: 10.3390/cancers16040726 -
Scientific Reports Oct 2023We evaluated whether the administration of kisspeptin-10 (Kp10) is capable of restoring gonadal function in hypothyroid male rats. Hypothyroidism was induced with...
We evaluated whether the administration of kisspeptin-10 (Kp10) is capable of restoring gonadal function in hypothyroid male rats. Hypothyroidism was induced with 6-propyl-2-thiouracil (PTU) for three months. In the last month, half of the hypothyroid animals were treated with Kp10. Hypothyroidism reduced testicular and sex gland mass, decreased the proliferation of the seminiferous epithelium, and compromised sperm morphology, motility, and vigor. A decrease in plasma LH and testosterone levels and an increase in prolactin secretion were observed in the hypothyroid rats. Hypothyroidism reduced Kiss1 and Kiss1r protein and gene expression and Star and Cyp11a1 mRNA levels in the testis. Furthermore, it reduced Lhb, Prl, and Drd2 and increased Tshb and Gnrhr expression in the pituitary. In the hypothalamus, hypothyroidism increased Pdyn and Kiss1r while reducing Gnrh1. Kp10 treatment in hypothyroid rats restored testicular and seminal vesicle morphology, improved sperm morphology and motility, reversed high prolactin levels, and increased LH and testosterone levels. In addition, Kp10 increased testicular expression of Kiss1, Kiss1r, Fshr, and Nr5a1 and pituitary Kiss1 expression. Our findings describe the inhibitory effects of hypothyroidism on the male gonadal axis and sperm quality and demonstrate that Kp10 treatment reverses high prolactin levels and improves gonadal function and sperm quality in hypothyroid rats.
Topics: Rats; Animals; Male; Kisspeptins; Prolactin; Luteinizing Hormone; Receptors, Kisspeptin-1; Semen; Hypothyroidism; Testis; Testosterone
PubMed: 37798396
DOI: 10.1038/s41598-023-44056-z -
International Journal of Molecular... Nov 2023Pituitary neuroendocrine tumors (PitNETs) are divided into multiple histological subtypes, which determine their clinical and biological variable behavior. Despite their...
Pituitary neuroendocrine tumors (PitNETs) are divided into multiple histological subtypes, which determine their clinical and biological variable behavior. Despite their benign evolution, in some cases, prolactin (PRL) and growth hormone (GH)-secreting PitNETs may have aggressive behavior. In this study, we investigated the potential predictive role of ER∝, alongside the clinicopathological classification of PitNETs (tumor diameter, tumor type, and tumor grade). A retrospective study was conducted with 32 consecutive cases of PRL- and mixed GH- and PRL-secreting PitNETs (5 patients with prolactinomas and 27 with acromegaly, among them, 7 patients with GH- and PRL- co-secretion) who underwent transsphenoidal intervention. Tumor specimens were histologically and immunohistochemical examined: anterior pituitary hormones, ki-67 labeling index, CAM 5.2, and ER∝; ER∝ expression was correlated with basal PRL levels at diagnosis (rho = 0.60, < 0.01) and postoperative PRL levels (rho = 0.58, < 0.001). In our study, the ER∝ intensity score was lower in female patients. Postoperative maximal tumor diameter correlated with Knosp grade ( = 0.02); CAM 5.2 pattern (densely/sparsely granulated/mixed densely and sparsely granulated) was correlated with postoperative PRL level ( = 0.002), and with ki-67 ( < 0.001). The IGF1 level at diagnosis was correlated with the postoperative GH nadir value in the oral glucose tolerance test (OGTT) (rho = 0.52, < 0.05). Also, basal PRL level at diagnosis was correlated with postoperative tumor diameter ( = 0.63, < 0.001). At univariate logistic regression, GH nadir in OGTT test at diagnostic, IGF1, gender, and invasion were independent predictors of remission for mixed GH- and PRL-secreting Pit-NETs; ER∝ can be used as a prognostic marker and loss of ER∝ expression should be considered a sign of lower differentiation and a likely indicator of poor prognosis. A sex-related difference can be considered in the evolution and prognosis of these tumors, but further studies are needed to confirm this hypothesis.
Topics: Humans; Female; Adenoma; Retrospective Studies; Ki-67 Antigen; Pituitary Neoplasms; Prolactinoma; Prolactin; Neuroendocrine Tumors
PubMed: 38003353
DOI: 10.3390/ijms242216162 -
Scientific Reports Sep 2023Preoperative homeostasis of sex hormones in testicular germ cell tumor (TGCT) patients is scarcely characterized. We aimed to explore regulation of sex hormones and...
Preoperative homeostasis of sex hormones in testicular germ cell tumor (TGCT) patients is scarcely characterized. We aimed to explore regulation of sex hormones and their implications for histopathological parameters and prognosis in TGCT using a data-driven explorative approach. Pre-surgery serum concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), estradiol (E2) and prolactin were measured in a retrospective multicenter TGCT cohort (n = 518). Clusters of patients were defined by latent class analysis. Clinical, pathologic and survival parameters were compared between the clusters by statistical hypothesis testing, Random Forest modeling and Peto-Peto test. Cancer tissue expression of sex hormone-related genes was explored in the publicly available TCGA cohort (n = 149). We included 354 patients with pure seminoma and 164 patients with non-seminomatous germ cell tumors (NSGCT), with a median age of 36 years. Three hormonal clusters were defined: 'neutral' (n = 228) with normal sex hormone homeostasis, 'testicle' (n = 91) with elevated T and E2, low pituitary hormones, and finally 'pituitary' subset (n = 103) with increased FSH and LH paralleled by low-to-normal levels of the gonadal hormones. Relapse-free survival in the hormonal subsets was comparable (p = 0.64). Cancer tissue expression of luteinizing hormone- and follicle-stimulating hormone-coding genes was significantly higher in seminomas, while genes of T and E2 biosynthesis enzymes were strongly upregulated in NSGCT. Substantial percentages of TGCT patients are at increased risk of sex hormone dysfunction at primary diagnosis before orchiectomy. TGCT may directly influence systemic hormonal homeostasis by in-situ synthesis of sex hormones.
Topics: Humans; Male; Adult; Neoplasm Recurrence, Local; Testicular Neoplasms; Gonadal Steroid Hormones; Neoplasms, Germ Cell and Embryonal; Luteinizing Hormone; Seminoma; Follicle Stimulating Hormone, Human
PubMed: 37669975
DOI: 10.1038/s41598-023-41915-7 -
International Journal of Molecular... Dec 2023Tuberoinfundibular dopamine (TIDA) neurons have cell bodies located in the arcuate nucleus of the mediobasal hypothalamus. They project to the external zone of the... (Review)
Review
Tuberoinfundibular dopamine (TIDA) neurons have cell bodies located in the arcuate nucleus of the mediobasal hypothalamus. They project to the external zone of the median eminence, and the dopamine (DA) released there is carried by the hypophysial portal vasculature to the anterior pituitary. The DA then activates D2 receptors to inhibit prolactin (PRL) secretion from lactotrophs. The TIDA neuronal population is the principal regulatory factor controlling PRL secretion. The neuroendocrine role subserved by TIDA neurons sets them apart from other dopaminergic populations like the nigrostriatal and mesolimbic DA neurons. TIDA neurons exhibit intrinsic oscillatory fluctuations in their membrane potential that give rise to phasic firing and bursting activity. TIDA neuronal activity is sexually differentiated and modulated by gonadal hormones and PRL, as well as an array of small molecule and peptide neurotransmitters. This review covers these characteristics.
Topics: Dopamine; Dopaminergic Neurons; Arcuate Nucleus of Hypothalamus; Cell Communication; Cell Differentiation
PubMed: 38203281
DOI: 10.3390/ijms25010110 -
Przeglad Menopauzalny = Menopause Review Dec 2023To detect the relationship between 25(OH)D and hypothyroidism in adolescents.
INTRODUCTION
To detect the relationship between 25(OH)D and hypothyroidism in adolescents.
MATERIAL AND METHODS
A total of 180 adolescents were included in the current study, which was conducted in West Kazakhstan (Aktobe) over 2 years. After thorough evaluation, blood samples were collected from the studied participants to measure the thyroid stimulating hormone (TSH), free thyroxine (T4), prolactin, glycosylated haemoglobin, and 25(OH)D. Participants were classified into a 25(OH)D-deficient group (study group) and controls. MedCalc and correlation analysis (Pearson's correlation) were used to detect the odds of hypothyroidism and the relationship between 25(OH)D and adolescents' hypothyroidism, respectively.
RESULTS
Thyroid-stimulating hormone was statistically higher in the 25(OH)D-deficient group than in the normal controls (3.71 ±1.4 mIU/ml vs. 2.67 ±0.99) ( = 0.0006), and the free T4 was statistically lower in the 25(OH)D-deficient group than in normal controls (1.4 ±0.56 ng/ml vs. 1.5 ±0.4) ( = 0.0008). The 25(OH)D deficient group had higher odds of subclinical (OR 4.89; = 0.016), and clinical hypothyroidism (OR 4.3; = 0.013) compared to controls. A significant negative correlation between the 25(OH)D and TSH ( = -0.793; < 0.00001), and a significant positive correlation between the 25(OH)D and free T4 ( 0.55; < 0.00001) were detected in this study.
CONCLUSIONS
The thyroid-stimulating hormone was statistically higher and the free T4 was statistically lower in the 25(OH)D-deficient group than in normal controls. The 25(OH)D-deficient group had higher odds of both subclinical and clinical hypothyroidism compared to controls. A significant negative correlation between the 25(OH)D and TSH, and a significant positive correlation between the 25(OH)D and the free T4 were detected in this study.
PubMed: 38239402
DOI: 10.5114/pm.2023.133280 -
Annals of Clinical Microbiology and... Nov 2023In the diagnosis of bloodstream infection (BSI), various inflammatory markers such as C-reactive protein (CRP), procalcitonin (PCT), interleukins (IL), white blood cell...
BACKGROUND
In the diagnosis of bloodstream infection (BSI), various inflammatory markers such as C-reactive protein (CRP), procalcitonin (PCT), interleukins (IL), white blood cell count (WBC), neutrophil percentage (NE%), platelet count (PLT), and erythrocyte sedimentation rate (ESR) have been extensively utilized. However, their specific roles in distinguishing BSI from local bacterial infection (LBI) and in classifying BSI pathogens remain uncertain.
METHODS
A historical cohort study was conducted, involving the enrollment of 505 patients with BSI and 102 patients with LBI. To validate the reliability of the clinical data obtained from this cohort, mouse models of BSI were utilized.
RESULTS
Our findings revealed that patients with BSI had significantly higher levels of inflammatory markers, including CRP, PCT, IL-6, IL-10, WBC, NE%, and ESR, compared to those with LBI (p < 0.05). The receiver operating characteristic (ROC) curve analysis demonstrated that CRP, PCT, IL-6, IL-10, ESR and NE% exhibited excellent diagnostic efficacy for BSI. Additionally, we observed significant differences in CRP, PCT, IL-6, and IL-10 levels between patients with BSI caused by Gram-positive bacteria (GP-BSI) and Gram-negative bacteria (GN-BSI), but no significant variations were found among specific bacterial species. Furthermore, our study also found that CRP, PCT, and IL-10 have good discriminatory ability for vancomycin-resistant Enterococcus (VRE), but they show no significant diagnostic efficacy for other multidrug-resistant organisms (MDROs) such as carbapenem-resistant Enterobacteriaceae (CRE), carbapenem-resistant Pseudomonas aeruginosa (CRPA), and methicillin-resistant Staphylococcus aureus (MRSA). In our mouse model experiments, we observed a remarkable increase in PCT, IL-6, and IL-10 levels in mice with GN-BSI compared to those with GP-BSI.
CONCLUSION
Our study has confirmed that PCT, IL-6, and IL-10 are efficient biomarkers for distinguishing between BSI and LBI. Furthermore, they can be utilized to classify BSI pathogens and differentiate between VRE and vancomycin-susceptible Enterococcus. These findings are extremely valuable for clinicians as they enable timely initiation of empiric antibiotic therapies and ultimately lead to improved clinical outcomes for patients with BSI.
Topics: Animals; Humans; Mice; Bacteremia; Bacterial Infections; Biomarkers; Blood Sedimentation; Interleukin-10; Interleukin-6; Prolactin; Retrospective Studies; C-Reactive Protein
PubMed: 37986183
DOI: 10.1186/s12941-023-00653-4