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BMC Endocrine Disorders Jun 2024An increase of IGF-1 has been reported during therapy with dopamine agonists (DA) for prolactinomas; in such cases a correct diagnosis is pivotal to avoid an unnecessary...
PURPOSE
An increase of IGF-1 has been reported during therapy with dopamine agonists (DA) for prolactinomas; in such cases a correct diagnosis is pivotal to avoid an unnecessary reduction or withdrawal of DA, which are needed to maintain normal prolactin levels. This study was aimed to measure IGF-1 levels, at baseline and during follow-up, in a cohort of patients with prolactinoma, treated with cabergoline, stratified by body mass index.
METHODS
We retrospectively enrolled 35 patients (15 F/20 M; age m ± SD, years: 43.4 ± 13.7) with prolactinoma (21 microadenomas and 14 macroadenomas) who were followed-up at the Endocrinology Unit, in Siena, and with available pituitary hormone assessment at baseline and during follow-up (m ± SD, years: 2.74 ± 0.55).
RESULTS
IGF-1 increased in the whole cohort, but remaining within normal range, except two patients, in whom acromegaly was ruled out with oral glucose tolerance test. After dividing patients by weight, this trend was confirmed only in subjects with overweight and obesity (OV/OB) (p = 0.04). Interestingly, the reduction of prolactin levels was significantly greater in the OV/OB compared to normal-weight patients (median decrease of 97.5% versus 88.2%, p = 0.04).
CONCLUSIONS
Since DA and normalization of prolactin are known to improve insulin sensitivity, we speculated they have favored the increase of IGF-1 in OV/OB. Our results should be confirmed and the hypothesis proven by further studies.
Topics: Humans; Prolactinoma; Insulin-Like Growth Factor I; Female; Male; Adult; Retrospective Studies; Dopamine Agonists; Pituitary Neoplasms; Middle Aged; Cabergoline; Body Weight; Follow-Up Studies; Prolactin; Body Mass Index; Prognosis
PubMed: 38902646
DOI: 10.1186/s12902-024-01622-4 -
Cureus May 2024The aim of this study is to investigate sexual dysfunctions (SDs) and related factors in patients with schizophrenia and bipolar disorder receiving pharmacotherapy.
OBJECTIVE
The aim of this study is to investigate sexual dysfunctions (SDs) and related factors in patients with schizophrenia and bipolar disorder receiving pharmacotherapy.
METHODS
This study included 111 patients. The Scale for the Assessment of Positive Symptoms (SAPS), the Scale for the Assessment of Negative Symptoms (SANS), and the Calgary Depression Scale for Schizophrenia (CDSS) were applied to the schizophrenia, and the Young Mania Rating Scale (YMRS) and Hamilton Depression Rating Scale (HAM-D) to the bipolar patient group. The sociodemographic data form and the Arizona Sexual Experiences Scale (ASEX) were applied to both of the patient groups. Blood was drawn from all patients to evaluate the indicated gene polymorphisms and evaluate prolactin levels.
RESULTS
SD was detected in 45.9% (N = 34) of the schizophrenia group, and 59.5% (N = 22) in the bipolar disorder group. SD was significantly higher in elderly patients and patients with a high smoking amount and low education levels. The eNOS -786T>C T allele frequency was found to be significantly higher in patients with SD. The logistic regression analysis determined that eNOS -786T>C CT and TT genotypes increased the risk of SD.
CONCLUSION
In this study, the high rates of SD in patients with schizophrenia and bipolar disorder, and the presence of modifiable factors that influence the presence of SD, suggest that SD should be given more attention in these patient groups. On the other hand, the high rate of SD in patients with the eNOS -786T>C T allele indicates the importance of carrying out new studies investigating the factors affecting the enzyme activity in this genotype. There is a need for more studies on eNOS genotypes and enzyme activites in this area.
PubMed: 38899233
DOI: 10.7759/cureus.60654 -
Journal of Experimental & Clinical... Jun 2024Though tamoxifen achieves success in treating estrogen receptor α (ERα)-positive breast cancer, the followed development of tamoxifen resistance is a common challenge...
BACKGROUND
Though tamoxifen achieves success in treating estrogen receptor α (ERα)-positive breast cancer, the followed development of tamoxifen resistance is a common challenge in clinic. Signals downstream of prolactin receptor (PRLR) could synergize with ERα in breast cancer progression. However, the potential effect of targeting PRL-PRLR axis combined with tamoxifen has not been thoroughly investigated.
METHODS
High-throughput RNA-seq data obtained from TCGA, Metabric and GEO datasets were analyzed to explore PRLR expression in breast cancer cell and the association of PRLR expression with tamoxifen treatment. Exogenous or PRL overexpression cell models were employed to investigate the role of activated PRLR pathway in mediating tamoxifen insensitivity. Immunotoxin targeting PRLR (N8-PE24) was constructed with splicing-intein technique, and the efficacy of N8-PE24 against breast cancer was evaluated using in vitro and in vivo methods, including analysis of cells growth or apoptosis, 3D spheroids culture, and animal xenografts.
RESULTS
PRLR pathway activated by PRL could significantly decrease sensitivity of ERα-positive breast cancer cells to tamoxifen. Tamoxifen treatment upregulated transcription of PRLR and could induce significant accumulation of PRLR protein in breast cancer cells by alkalizing lysosomes. Meanwhile, tamoxifen-resistant MCF7 achieved by long-term tamoxifen pressure exhibited both upregulated transcription and protein level of PRLR. Immunotoxin N8-PE24 enhanced sensitivity of breast cancer cells to tamoxifen both in vitro and in vivo. In xenograft models, N8-PE24 significantly enhanced the efficacy of tamoxifen and paclitaxel when treating PRLR-positive triple-negative breast cancer.
CONCLUSIONS
PRL-PRLR axis potentially associates with tamoxifen insensitivity in ERα-positive breast cancer cells. N8-PE24 could inhibit cell growth of the breast cancers and promote drug sensitivity of PRLR-positive breast cancer cells to tamoxifen and paclitaxel. Our study provides a new perspective for targeting PRLR to treat breast cancer.
Topics: Tamoxifen; Humans; Female; Breast Neoplasms; Animals; Receptors, Prolactin; Mice; Immunotoxins; Xenograft Model Antitumor Assays; Cell Line, Tumor; Drug Resistance, Neoplasm; Cell Proliferation; Apoptosis
PubMed: 38898487
DOI: 10.1186/s13046-024-03099-4 -
The Lancet. Child & Adolescent Health Jul 2024The degree of physiological responses to individual antipsychotic drugs is unclear in children and adolescents. With network meta-analysis, we aimed to investigate the... (Meta-Analysis)
Meta-Analysis Comparative Study
BACKGROUND
The degree of physiological responses to individual antipsychotic drugs is unclear in children and adolescents. With network meta-analysis, we aimed to investigate the effects of various antipsychotic medications on physiological variables in children and adolescents with neuropsychiatric and neurodevelopmental conditions.
METHODS
For this network meta-analysis, we searched Medline, EMBASE, PsycINFO, Web of Science, and Scopus from database inception until Dec 22, 2023, and included randomised controlled trials comparing antipsychotics with placebo in children or adolescents younger than 18 years with any neuropsychiatric and neurodevelopmental condition. Primary outcomes were mean change from baseline to end of acute treatment in bodyweight, BMI, fasting glucose, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, prolactin, heart rate, systolic blood pressure (SBP), and QT interval corrected for heart rate (QTc) for patients receiving either active treatment or placebo. For multigroup trials reporting several doses, we calculated a summary value for each physiological variable for all doses. After transitivity assessment, we fitted frequentist random-effects network meta-analyses for all comparisons in the network. A Kilim plot was used to summarise the results for all treatments and outcomes, providing information regarding the strength of the statistical evidence of treatment effects, using p values. Network heterogeneity was assessed with τ, risk of bias of individual trials was assessed with the Cochrane Collaboration's Tool for Assessing Risk of Bias, and the credibility of findings from each network meta-analysis was assessed with the Confidence in Network Meta-Analysis (CINEMA) app. This study is registered on PROSPERO (CRD42021274393).
FINDINGS
Of 6676 studies screened, 47 randomised controlled trials were included, which included 6500 children (mean age 13·29 years, SD 2·14) who received treatment for a median of 7 weeks (IQR 6-8) with either placebo (n=2134) or one of aripiprazole, asenapine, blonanserin, clozapine, haloperidol, lurasidone, molindone, olanzapine, paliperidone, pimozide, quetiapine, risperidone, or ziprasidone (n=4366). Mean differences for bodyweight change gain compared with placebo ranged from -2·00 kg (95% CI -3·61 to -0·39) with molindone to 5·60 kg (0·27 to 10·94) with haloperidol; BMI -0·70 kg/m (-1·21 to -0·19) with molindone to 2·03 kg/m (0·51 to 3·55) with quetiapine; total cholesterol -0·04 mmol/L (-0·39 to 0·31) with blonanserin to 0·35 mmol/L (0·17 to 0·53) with quetiapine; LDL cholesterol -0·12 mmol/L (-0·31 to 0·07) with risperidone or paliperidone to 0·17 mmol/L (-0·06 to 0·40) with olanzapine; HDL cholesterol 0·05 mmol/L (-0·19 to 0·30) with quetiapine to 0·48 mmol/L (0·18 to 0·78) with risperidone or paliperidone; triglycerides -0·03 mmol/L (-0·12 to 0·06) with lurasidone to 0·29 mmol/L (0·14 to 0·44) with olanzapine; fasting glucose from -0·09 mmol/L (-1·45 to 1·28) with blonanserin to 0·74 mmol/L (0·04 to 1·43) with quetiapine; prolactin from -2·83 ng/mL (-8·42 to 2·75) with aripiprazole to 26·40 ng/mL (21·13 to 31·67) with risperidone or paliperidone; heart rate from -0·20 bpm (-8·11 to 7·71) with ziprasidone to 12·42 bpm (3·83 to 21·01) with quetiapine; SBP from -3·40 mm Hg (-6·25 to -0·55) with ziprasidone to 10·04 mm Hg (5·56 to 14·51) with quetiapine; QTc from -0·61 ms (-1·47 to 0·26) with pimozide to 0·30 ms (-0·05 to 0·65) with ziprasidone.
INTERPRETATION
Children and adolescents show varied but clinically significant physiological responses to individual antipsychotic drugs. Treatment guidelines for children and adolescents with a range of neuropsychiatric and neurodevelopmental conditions should be updated to reflect each antipsychotic drug's distinct profile for associated metabolic changes, alterations in prolactin, and haemodynamic alterations.
FUNDING
UK Academy of Medical Sciences, Brain and Behaviour Research Foundation, UK National Institute of Health Research, Maudsley Charity, the Wellcome Trust, Medical Research Council, National Institute of Health and Care Research Biomedical Centre at King's College London and South London and Maudsley NHS Foundation Trust, the Italian Ministry of University and Research, the Italian National Recovery and Resilience Plan, and Swiss National Science Foundation.
Topics: Humans; Antipsychotic Agents; Child; Adolescent; Network Meta-Analysis; Randomized Controlled Trials as Topic; Mental Disorders; Heart Rate; Blood Pressure
PubMed: 38897716
DOI: 10.1016/S2352-4642(24)00098-1 -
Frontiers in Endocrinology 2024Gonadotropin-releasing hormone (GnRH) is a key stimulator for gonadotropin secretion in the pituitary and its pivotal role in reproduction is well conserved in...
Differential involvement of cAMP/PKA-, PLC/PKC- and Ca/calmodulin-dependent pathways in GnRH-induced prolactin secretion and gene expression in grass carp pituitary cells.
Gonadotropin-releasing hormone (GnRH) is a key stimulator for gonadotropin secretion in the pituitary and its pivotal role in reproduction is well conserved in vertebrates. In fish models, GnRH can also induce prolactin (PRL) release, but little is known for the corresponding effect on PRL gene expression as well as the post-receptor signalling involved. Using grass carp as a model, the functional role of GnRH and its underlying signal transduction for PRL regulation were examined at the pituitary level. Using laser capture microdissection coupled with RT-PCR, GnRH receptor expression could be located in carp lactotrophs. In primary cell culture prepared from grass carp pituitaries, the native forms of GnRH, GnRH2 and GnRH3, as well as the GnRH agonist [D-Arg, Pro, NEt]-sGnRH were all effective in elevating PRL secretion, PRL mRNA level, PRL cell content and total production. In pituitary cells prepared from the rostral pars distalis, the region in the carp pituitary enriched with lactotrophs, GnRH not only increased cAMP synthesis with parallel CREB phosphorylation and nuclear translocation but also induced a rapid rise in cytosolic Ca by Ca influx via L-type voltage-sensitive Ca channel (VSCC) with subsequent CaM expression and NFAT dephosphorylation. In carp pituitary cells prepared from whole pituitaries, GnRH-induced PRL secretion was reduced/negated by inhibiting cAMP/PKA, PLC/PKC and Ca/CaM/CaMK-II pathways but not the signalling events via IP and CaN/NFAT. The corresponding effect on PRL mRNA expression, however, was blocked by inhibiting cAMP/PKA/CREB/CBP and Ca/CaM/CaN/NFAT signalling but not PLC/IP/PKC pathway. At the pituitary cell level, activation of cAMP/PKA pathway could also induce CaM expression and Ca influx via VSCC with parallel rises in PRL release and gene expression in a Ca/CaM-dependent manner. These findings, as a whole, suggest that the cAMP/PKA-, PLC/PKC- and Ca/CaM-dependent cascades are differentially involved in GnRH-induced PRL secretion and PRL transcript expression in carp lactotrophs. During the process, a functional crosstalk between the cAMP/PKA- and Ca/CaM-dependent pathways may occur with PRL release linked with CaMK-II and PKC activation and PRL gene transcription caused by nuclear action of CREB/CBP and CaN/NFAT signalling.
Topics: Animals; Carps; Gonadotropin-Releasing Hormone; Prolactin; Pituitary Gland; Protein Kinase C; Cyclic AMP-Dependent Protein Kinases; Calcium; Type C Phospholipases; Cyclic AMP; Signal Transduction; Calmodulin; Cells, Cultured; Gene Expression
PubMed: 38894746
DOI: 10.3389/fendo.2024.1399274 -
Foods (Basel, Switzerland) May 2024Breast milk serves as the primary source of nourishment for newborns. In cases of low milk production, one approach to address this challenge involves the consumption of...
Breast milk serves as the primary source of nourishment for newborns. In cases of low milk production, one approach to address this challenge involves the consumption of lactagogues. Chicken-herb essence, a beverage rich in protein, amino acids, and minerals, presents itself as a viable option to supplement a lactating mother's diet, particularly in terms of protein intake. This study aimed to evaluate the effects of chicken-herb essence on prolactin and lactoferrin in lactating rats. Furthermore, the study also assessed the lactagogue effect on IgA in offspring. The experimental research method used a completely randomized design. The animal models in this study were female Sprague Dawley rats. The result showed that there was an increase in milk production, as seen from the results of the lactagogue effect. The highest increase in prolactin and lactoferrin was obtained in treatment group II (TG II). The increases in prolactin and lactoferrin of TG II were 214.18 ± 71.99 and 904.02 ± 435.35 pg/mL, respectively. The lactagogue test showed that TG II haspotency as a milk-booster. Testing the blood serum of offspring showed that the highest concentration of IgA was also found in TG II at 398.34 ± 214.85 pg/mL.
PubMed: 38890832
DOI: 10.3390/foods13111603 -
Cell Death Discovery Jun 2024As the mean age of first-time mothers increases in the industrialized world, inquiries into causes of human reproductive senescence have followed. Rates of ovulatory...
As the mean age of first-time mothers increases in the industrialized world, inquiries into causes of human reproductive senescence have followed. Rates of ovulatory dysfunction and oocyte aneuploidy parallel chronological age, but poor reproductive outcomes in women older than 35 years are also attributed to endometrial senescence. The current studies, using primary human endometrial stromal cell (ESC) cultures as an in vitro model for endometrial aging, characterize the proinflammatory cytokine, IL-1β-mediated and passage number-dependent effects on ESC phenotype. ESC senescence was accelerated by incubation with IL-1β, which was monitored by RNA sequencing, ELISA, immunocytochemistry and Western blotting. Senescence associated secreted phenotype (SASP) proteins, IL-1β, IL-6, IL-8, TNF-α, MMP3, CCL2, CCL5, and other senescence-associated biomarkers of DNA damage (p16, p21, HMGB1, phospho-γ-histone 2 A.X) were noted to increase directly in response to 0.1 nM IL-1β stimulation. Production of the corresponding SASP proteins increased further following extended cell passage. Using enzyme inhibitors and siRNA interference, these effects of IL-1β were found to be mediated via the c-Jun N-terminal kinase (JNK) signaling pathway. Hormone-induced ESC decidualization, classical morphological and biochemical endocrine responses to estradiol, progesterone and cAMP stimulation (prolactin, IGFBP-1, IL-11 and VEGF), were attenuated pari passu with prolonged ESC passaging. The kinetics of differentiation responses varied in a biomarker-specific manner, with IGFBP-1 and VEGF secretion showing the largest and smallest reductions, with respect to cell passage number. ESC hormone responsiveness was most robust when limited to the first six cell passages. Hence, investigation of ESC cultures as a decidualization model should respect this limitation of cell aging. The results support the hypotheses that "inflammaging" contributes to endometrial senescence, disruption of decidualization and impairment of fecundity. IL-1β and the JNK signaling pathway are pathogenetic targets amenable to pharmacological correction or mitigation with the potential to reduce endometrial stromal senescence and enhance uterine receptivity.
PubMed: 38879630
DOI: 10.1038/s41420-024-02048-6 -
International Journal of Surgery Case... Jul 2024Ectopic pituitary neuroendocrine tumor (EPNET) is a very rare entity, seldom with apoplexy evolution. Only three cases of intracranial ectropic pituitary neuroendocrine...
INTRODUCTION AND IMPORTANCE
Ectopic pituitary neuroendocrine tumor (EPNET) is a very rare entity, seldom with apoplexy evolution. Only three cases of intracranial ectropic pituitary neuroendocrine tumor apoplexy were reported in the literature.
CASE PRESENTATION
We report the case of a 45-year-old woman with a history of amenorrhea, and headaches. Neuroimaging showed a very aggressive giant mass within the clivus with the invasion of the sphenoidal sinus and encasement of internal carotid arteries with an empty sella. Endocrinology work-up revealed an exceedingly high level of prolactin surprisingly without galactorrhea. Immunohistochemical analysis after an endonasal biopsy confirmed the diagnosis of prolactinoma. One month after Cabergoline initiation, an apoplexy of the ectopic pituitary neuroendocrine tumor occurred. Conservational management with a decrease in cabergoline dose was performed.
DISCUSSION
This article highlights data from various cases reported in the literature in addition to our case to confirm the extreme rarity of apoplexy as a complication of EPNET.
CONCLUSION
Pituitary apoplexy in ectopic pituitary neuroendocrine tumor is extremely rare. Therefore, in case of unusual localization of pituitary neuroendocrine tumor, a thorough follow-up is necessary to detect complications and ensure early management.
PubMed: 38878728
DOI: 10.1016/j.ijscr.2024.109874 -
Neuropharmacology Jun 2024Kappa opioid receptors (KORs) are implicated in the pathophysiology of various psychiatric and neurological disorders creating interest in targeting the KOR system for...
Kappa opioid receptors (KORs) are implicated in the pathophysiology of various psychiatric and neurological disorders creating interest in targeting the KOR system for therapeutic purposes. Accordingly, navacaprant (NMRA-140) is a potent, selective KOR antagonist being evaluated as a treatment for major depressive disorder. In the present report, we have extended the pharmacological characterization of navacaprant by further demonstrating its selective KOR antagonist properties and confirming its lack of agonist activity at KORs and related targets involved in opioid-related abuse. Using CHO-K1 cells expressing human KOR, mu (MOR), or delta (DOR) opioid receptors, navacaprant demonstrated selective antagonist properties at KOR (IC = 0.029 μM) versus MOR (IC = 3.3 μM) and DOR (IC > 10 μM) in vitro. In vivo, navacaprant (10-30 mg/kg, i.p.) dose-dependently abolished KOR-agonist induced analgesia in the mouse tail-flick assay. Additionally, navacaprant (10, 30 mg/kg, p.o.) significantly reduced KOR agonist-stimulated prolactin release in mice and rats, confirming KOR antagonism in vivo. Navacaprant showed no agonist activity at any opioid receptor subtype (EC > 10 μM) in vitro and exhibited no analgesic effect in the tail-flick assays at doses ≤100 mg/kg, p.o. thereby confirming a lack of opioid receptor agonist activity in vivo. Importantly, navacaprant did not alter extracellular dopamine concentrations in the nucleus accumbens shell of freely-moving rats following doses ≤100 mg/kg, p.o., whereas morphine (10, 20 mg/kg, i.p.) significantly increased dopamine levels. These results demonstrate that navacaprant is a KOR-selective antagonist with no pharmacological properties implicated in opioid-related abuse.
PubMed: 38876309
DOI: 10.1016/j.neuropharm.2024.110037