-
European Archives of... Aug 2023It has been hypothesised that secretory carcinoma of the salivary gland (SCsg) might have a lactational-like differentiation. Therefore, we aimed to assess the...
PURPOSE
It has been hypothesised that secretory carcinoma of the salivary gland (SCsg) might have a lactational-like differentiation. Therefore, we aimed to assess the immunoexpression of breast hormonal receptors and milk-related proteins in cases of SCsg and other salivary gland tumours with prominent secretory activity.
METHODS
Immunohistochemistry against prolactin and growth hormone receptors, lactoferrin, human milk fat globule 1, MUC 1 and MUC4 was performed in twelve cases of SCsg and 47 other salivary gland tumours.
RESULTS
Most cases of SCsg were negative for prolactin and growth hormone receptors. All cases of SCsg showed enhanced membranous-cytoplasmic staining for human milk fat globule 1, a pattern seen in other tumour groups. Only SCsg showed widespread strong staining for lactoferrin, concomitantly in the cell compartment and secretion. The other positive tumour types exhibited restricted staining. MUC1 and MUC4 showed no distinct pattern of expression.
CONCLUSION
Although SCsg failed to demonstrate a complete lactational-like differentiation, lactoferrin showed a distinctive expression pattern in SCsg compared to other tumour types, which makes it a good marker to help in its differential diagnosis.
Topics: Humans; Lactoferrin; Prolactin; Receptors, Somatotropin; Biomarkers, Tumor; Salivary Glands; Carcinoma; Salivary Gland Neoplasms; Cell Differentiation
PubMed: 37227470
DOI: 10.1007/s00405-023-08023-8 -
The Journal of Pain May 2024Estimates suggest that only 24.9% of infants born in 2019 were exclusively breastfed before 6 months of age, despite the known health benefits of exclusive...
Estimates suggest that only 24.9% of infants born in 2019 were exclusively breastfed before 6 months of age, despite the known health benefits of exclusive breastfeeding. Breast and nipple pain is one of the primary determinants of exclusive breastfeeding. Environmental contributions to breastfeeding success have been reported extensively in the literature, but the contribution(s) of maternal genetics has yet to be discovered. The purpose of the study was to identify an association between pain and lactation-related gene variants with exclusive breastfeeding determinants. We selected 4 genes having single nucleotide polymorphisms (SNPs) with potential functional significance in breastfeeding and pain: prolactin receptor (PRLR), oxytocin receptor (OXTR), catechol-O-methyltransferase (COMT), and milk fat globule epidermal growth factor and factor V/VIII domain containing (MFGE8). We performed a cross-sectional secondary analysis of a longitudinal randomized controlled trial study, Promoting Self-Management of Breast and Nipple Pain with Biomarkers and Technology for Breastfeeding Women (NCT05262920). Breast and nipple pain, perceived insufficient milk, and breastfeeding self-efficacy were examined using total scale scores for the Brief Pain Inventory, Visual Analog Scale, H&H Lactation Scale, and the Breastfeeding Self-efficacy Scale-short form, respectively. Of the candidate genes examined, SNPs within COMT were significantly associated with breastfeeding-related outcomes. Specifically, COMT rs4633 and rs4680 minor allele carriers (T, A) reported higher breast and nipple pain intensity than women homozygous for the major allele (C, G). COMT is the most widely researched "pain gene" and has been linked to cold, postoperative, and postpartum pain. This study is the first to identify a contribution of COMT variants to breast and nipple pain and, as a result, to breastfeeding exclusivity. PERSPECTIVE: Two SNPs in the pain gene COMT are associated with breast and nipple pain. Clinically, a minor allele in COMT rs4633 and rs4680 may increase a woman's rating of moderate breast and nipple pain. TRIAL REGISTRATION: PROMPT was registered in ClinicalTrials.gov (protocol #NCT05262920).
PubMed: 38763257
DOI: 10.1016/j.jpain.2024.104568 -
Endocrinology Apr 2024Prolactin and its receptor (PRLr) in humans are significantly involved in breast cancer pathogenesis. The intermediate form of human PRLr (hPRLrI) is produced by...
Prolactin and its receptor (PRLr) in humans are significantly involved in breast cancer pathogenesis. The intermediate form of human PRLr (hPRLrI) is produced by alternative splicing and has a novel 13 amino acid tail ("I-tail") gain. hPRLrI induces significant proliferation and anchorage-independent growth of normal mammary epithelia in vitro when coexpressed with the long form hPRLr (hPRLrL). hPRLrL and hPRLrI coexpression is necessary to induce the transformation of mammary epithelia in vivo. The I-tail is associated with the ubiquitin-like protein neural precursor cell expressed developmentally downregulated protein 8. Treatment with the neural precursor cell expressed developmentally downregulated protein 8-activating enzyme inhibitor pevonedistat resulted in increased hPRLrL and the death of breast cancer cells. The goal of this study was to determine the function of the hPRLrI I-tail in hPRLrL/hPRLrI-mediated mammary transformation. hPRLrL/hPRLrI and hPRLrL/hPRLrIΔ13 (I-tail removal mutant) were delivered to MCF10AT cells. Cell proliferation was decreased when hPRLrI I-tail was removed. I-tail deletion decreased anchorage-independent growth and attenuated cell migration. The I-tail was involved in Ras/MAPK signaling but not PI3K/Akt signaling pathway as shown by western blot. I-tail removal resulted in decreased hPRLrI stability. RNA-sequencing data revealed that I-tail removal resulted in differential gene expression induced by prolactin. Ingenuity Pathway Analysis revealed that the activity of ERK was attenuated. Treatment of breast cancer cells with ERK1/2 inhibitor ulixertinib resulted in decreased colony-forming ability and less proliferation. These studies suggest that the hPRLrI I-tail contributed to breast oncogenesis and may be a promising target for the development of new breast cancer therapies.
Topics: Female; Humans; Breast Neoplasms; Carcinogenesis; Cell Line, Tumor; Cell Proliferation; Cell Transformation, Neoplastic; MAP Kinase Signaling System; Prolactin; ras Proteins; Receptors, Prolactin; Signal Transduction
PubMed: 38713636
DOI: 10.1210/endocr/bqae039 -
Cell Death & Disease Feb 2024Previous study showed that higher expression of prolactin (PRL) was found in CRPC samples compared with hormone-naive prostate cancer (HNPC) and benign prostatic...
Previous study showed that higher expression of prolactin (PRL) was found in CRPC samples compared with hormone-naive prostate cancer (HNPC) and benign prostatic hyperplasia (BPH) samples. We further investigate the function of PRL in prostate cancer (PCa) and explored its downstream effects. We found heterogeneous expression of the PRLR in clinical prostate samples. The VCaP and 22Rv1 cells exhibited PRLR expression. Among the downstream proteins, STAT5B was the dominant subtype in clinical samples and cell lines. Human recombinant PRL stimulation of PCa cells with PRLR expression resulted in increased phosphorylation of STAT5B(pSTAT5B) and progression of PCa in vitro and in vivo, and STAT5B knockdown can suppress the malignant behavior of PCa. To understand the mechanism further, we performed Bioinformatic analysis, ChIP qPCR, and luciferase reporter gene assay. The results revealed that ARRB2 was the transcription target gene of STAT5B, and higher expression of ARRB2 was related to higher aggression and poorer prognosis of PCa. Additionally, Gene set enrichment analysis indicated that higher expression of ARRB2 was significantly enriched in the MAPK signaling pathway. Immunohistochemistry (IHC) demonstrated elevated pSTAT5B, ARRB2, and pERK1/2 expression levels in CRPC tissues compared to HNPC and BPH. Mechanically, ARRB2 enhanced the activation of the MAPK pathway by binding to ERK1/2, thereby promoting the phosphorylation of ERK1/2 (pERK1/2). In conclusion, our study demonstrated that PRL stimulation can promote the progression of PCa through STAT5B/ARRB2 pathway and activation of MAPK signaling, which can be suppressed by intervention targeting STAT5B. Blockade of the STAT5B can be a potential therapeutic target for PCa.
Topics: Male; Humans; Prolactin; Prostatic Hyperplasia; Prostatic Neoplasms, Castration-Resistant; Prostatic Neoplasms; Receptors, Prolactin; Phosphorylation; Cell Line, Tumor; STAT5 Transcription Factor; beta-Arrestin 2
PubMed: 38341429
DOI: 10.1038/s41419-023-06362-2 -
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 -
Biomedicines Jul 2023The prediction of colorectal cancer (CRC) response to palliative chemotherapy (CTH) is still difficult. Patients at a higher risk of progression may benefit from more...
The Value of Prolactin, a Panel of Cytokines, and the Soluble Human Epidermal Growth Factor Receptor 2 in the Prediction of Rapid Progression and Shorter Survival during Palliative Chemotherapy of Colorectal Cancer Patients.
The prediction of colorectal cancer (CRC) response to palliative chemotherapy (CTH) is still difficult. Patients at a higher risk of progression may benefit from more aggressive treatment. This study assessed the predictive value of prolactin (PRL) and a panel of cytokines, chemokines, and growth factors for the risk of rapid progression in CRC patients starting palliative CTH. This study included 51 CRC patients initiating palliative CTH with up to 5-year follow-up, divided into rapid and non-rapid progressors. Serum samples were collected before CTH for assessment of a large panel of cytokines, chemokines, growth factors, and PRL via a multiplex method. Rapid progressors (N = 19) were characterized by increased baseline values of IL-8 and IP10 but decreased PRL levels. In addition, PRL below 18.2 ng/mL was a strong predictor of weight loss during CTH. Grade 3 (HR = 2.97; 95%CI: 1.48-5.98) and PRL level (HR = 0.96; 95%CI: 0.91-1.01) were independent risk factors of progression. We showed that CRC rapid progressors are characterized by decreased baseline PRL levels. In addition, increased baseline levels of IP-10, sHER-2, IL-6, and IL-8 may be associated with longer survival; however, larger studies are needed to confirm their predictive role in CRC patients.
PubMed: 37509653
DOI: 10.3390/biomedicines11072014 -
Animal Bioscience Apr 2024The objective of this study was to investigate the effects of prolactin (PRL) on the proliferation and apoptosis of ovine ovarian granulosa cells (GCs) and the secretion...
OBJECTIVE
The objective of this study was to investigate the effects of prolactin (PRL) on the proliferation and apoptosis of ovine ovarian granulosa cells (GCs) and the secretion of estrogen (E2) and progesterone (P4), as well as to explore the effects of PRL on related genes and proteins.
METHODS
We isolated ovarian GCs from 1-year-old small-tail Han sheep and identified PRL receptor (PRLR) on ovaries and follicle stimulating hormone receptor (FSHR) on ovarian GCs, respectively, using immunohistochemistry. PRL (0, 0.05, 0.50, 5.00 μg/mL) were added to GCs in vitro along with FSH, cell proliferation was measured by Cell Counting Kit-8 (CCK-8) and apoptosis by flow cytometry. The measurement of E2 and P4 content by ELISA after 24h and 48h. The expression of functional genes and proteins was identified by RT-qPCR and Western-blot after 24h.
RESULTS
PRLR was expressed in both follicular GCs and corpus luteum, whereas FSHR was expressed specifically. The proliferative activity was lower on day 1 while higher on day 4 and day 5. The apoptosis rate of GCs in the 0.05 μg/mL group was significantly higher than that in the control group after treatment with PRL for 24 h (p<0.05). Compared with the control group, the secretion of E2 in GCs was reduced significantly (p<0.05) in PRL treatment for 24h and 48h, while the secretion of P4 was significantly increased (p<0.05). The mRNA expression levels of PRLR, FSHR, LHR, CYP11A1, HSD3B7 and STAR were significantly higher than those in the control group (p<0.01), and the relative abundance of BCL2 in all PRL group were increased after PRL treatment.
CONCLUSION
PRL promoted the proliferation of GCs and supraphysiological concentrations inhibited apoptosis caused by down-regulation of BAX and up-regulation of BCL2. PRL inhibited E2 by down-regulating CYP19A1 and promoted P4 by up-regulating CYP11A1, STAR and HSD3B7.
PubMed: 38665071
DOI: 10.5713/ab.23.0448 -
Journal of Proteome Research Dec 2023Alzheimer's disease (AD) is the most prevalent form of dementia, disproportionately affecting women in disease prevalence and progression. Comprehensive analysis of the...
Alzheimer's disease (AD) is the most prevalent form of dementia, disproportionately affecting women in disease prevalence and progression. Comprehensive analysis of the serum proteome in a common AD mouse model offers potential in identifying possible AD pathology- and gender-associated biomarkers. Here, we introduce a multiplexed, nondepleted mouse serum proteome profiling via tandem mass-tag (TMTpro) labeling. The labeled sample was separated into 475 fractions using basic reversed-phase liquid chromatography (RPLC), which were categorized into low-, medium-, and high-concentration fractions for concatenation. This concentration-dependent concatenation strategy resulted in 128 fractions for acidic RPLC-tandem mass spectrometry (MS/MS) analysis, collecting ∼5 million MS/MS scans and identifying 3972 unique proteins (3413 genes) that cover a dynamic range spanning at least 6 orders of magnitude. The differential expression analysis between wild type and the commonly used AD model (5xFAD) mice exhibited minimal significant protein alterations. However, we detected 60 statistically significant (FDR < 0.05), sex-specific proteins, including complement components, serpins, carboxylesterases, major urinary proteins, cysteine-rich secretory protein 1, pregnancy-associated murine protein 1, prolactin, amyloid P component, epidermal growth factor receptor, fibrinogen-like protein 1, and hepcidin. The results suggest that our platform possesses the sensitivity and reproducibility required to detect sex-specific differentially expressed proteins in mouse serum samples.
Topics: Humans; Male; Mice; Female; Animals; Alzheimer Disease; Tandem Mass Spectrometry; Proteome; Reproducibility of Results; Chromatography, Reverse-Phase
PubMed: 37910662
DOI: 10.1021/acs.jproteome.3c00496 -
FEBS Open Bio Sep 2023Stress-related illnesses are linked to the onset and progression of renal diseases and depressive disorders. To investigate stress-induced changes in the renal...
Stress-related illnesses are linked to the onset and progression of renal diseases and depressive disorders. To investigate stress-induced changes in the renal transcriptome associated with the development of depressive behaviors, we generated here a chronic social defeat stress (CSDS) model of C57 BL/6 male mice and then performed RNA sequencing of the kidneys to obtain an inflammation-related transcriptome. Administration of the antidepressant drug fluoxetine (10 mg·kg ·day ) during CSDS induction could partially alleviate renal inflammation and reverse CSDS-induced depression-like behaviors. Moreover, fluoxetine also modulated gene expression of stress-related hormone receptors, including prolactin and melanin-concentrating hormone. These results suggest that CSDS can induce gene expression changes associated with inflammation in the kidney of C57 BL/6 male mice, and this inflammation can be treated effectively by fluoxetine.
Topics: Animals; Mice; Male; Fluoxetine; Antidepressive Agents; Depression; Inflammation; Kidney
PubMed: 37400956
DOI: 10.1002/2211-5463.13670 -
Current Alzheimer Research May 2024Dementia encompasses a range of neurodegenerative disorders characterized by cognitive decline and functional impairment. The identification of reliable biomarkers is... (Clinical Trial)
Clinical Trial
BACKGROUND
Dementia encompasses a range of neurodegenerative disorders characterized by cognitive decline and functional impairment. The identification of reliable biomarkers is essential for accurate diagnosis and gaining insights into the mechanisms underlying diseases.
OBJECTIVE
This study aimed to investigate the plasma biomarker profiles associated with Brain- Derived Neurotrophic Factor (BDNF), Oxytocin, Neuronal Pentraxin-1 (NPTX1), Triggering Receptor Expressed on Myeloid Cells 2 (TREM2), Tumor Necrosis Factor-alpha (TNF-alpha), Interleukin- 1 (IL-1), and Prolactin in Alzheimer's disease (AD), dementia with Lewy bodies (DLB), frontotemporal dementias (FTD), and healthy controls.
METHODS
Serum levels of the aforementioned biomarkers were analyzed in 23 AD, 28 DLB, 15 FTD patients recruited from outpatient units, and 22 healthy controls. Diagnostic evaluations followed established criteria, and standardized clinical tests were conducted. Blood samples were collected and analyzed using ELISA and electrochemiluminescence immunoassay methods.
RESULTS
Serum BDNF and oxytocin levels did not significantly differ across groups. NPTX1, TREM2, TNF-alpha, and IL-1 levels also did not show significant differences among dementia groups. However, prolactin levels exhibited distinct patterns, with lower levels in male DLB patients and higher levels in female AD patients compared to controls.
CONCLUSION
The study findings suggest potential shared mechanisms in dementia pathophysiology and highlight the importance of exploring neuroendocrine responses, particularly in AD and DLB. However, further research is warranted to elucidate the role of these biomarkers in dementia diagnosis and disease progression.
PubMed: 38803182
DOI: 10.2174/0115672050313419240520051751