Bisphenol-A (BPA) has been reported to be associated to female infertility. Indeed, BPA has been found to be more frequently detected in infertile women thus leading to hypothesize a possible effect ...of BPA on natural conception and spontaneous fecundity. In addition, in procedures of medically assisted reproduction BPA exposure has been found to be negatively associated with peak serum estradiol levels during gonadotropin stimulation, number of retrieved oocytes, number of normally fertilized oocytes and implantation. BPA deleterious effects are more critical during perinatal exposure, causing dysregulation of hypothalamic-pituitary-ovarian axis in pups and adults, with a precocious maturation of the axis through a damage of GnRH pulsatility, gonadotropin signaling and sex steroid hormone production. Further, BPA exposure during early lifestage may have a transgenerational effect predisposing the subsequent generations to the risk of developing BPA related disease. Experimental studies suggested that prenatal, perinatal and postnatal exposure to BPA can impair several steps of ovarian development, induce ovarian morphology rearrangement and impair ovarian function, particularly folliculogenesis, as well as can impair uterus morphology and function, in female adult animal and offspring. Finally, studies carried out in animal models have been reported the occurrence of endometriosis-like lesions after BPA exposure. Moreover, BPA exposure has been described to encourage the genesis of PCOS-like abnormalities through the impairment of the secretion of sex hormones affecting ovarian morphology and functions, particularly folliculogenesis. The current manuscript summarizes the evidence regarding the association between BPA exposure and female infertility, reviewing both clinical and preclinical studies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
ContextThe most frequent cause of death in acromegaly is cardiomyopathy.ObjectiveTo evaluate determinants of acromegalic cardiomyopathy.DesignObservational, open, controlled, retrospective ...study.SubjectsTwo hundred and five patients with newly diagnosed active acromegaly (108 women and 97 men; median age 44 years) and 410 non-acromegalic subjects sex- and age-matched with the patients.Main outcome measuresLeft ventricular (LV) mass index (LVMi), transmitral inflow early-to-atrial (E/A) peak velocity ratio, and LV ejection fraction (LVEF) were measured by Doppler echocardiography to determine the prevalence of LV hypertrophy (LVH), diastolic and systolic dysfunction. The role of age, estimated disease duration, body mass index, GH and IGF1 levels, systolic and diastolic blood pressure, lipid profile and glucose tolerance in determining different features of the acromegalic cardiomyopathy was investigated.ResultsCompared with controls, the patients had lower E/A, LVEF, high-density lipoprotein (HDL)-cholesterol levels and higher LVMi, total- and low-density lipoprotein (LDL)-cholesterol, triglycerides, glucose and insulin levels, homeostatic model assessment of insulin resistance (HOMA-R) and HOMA-β. The relative risk to develop mild (odds ratio (OR)=1.67 (1.05–2.66); P=0.027) or severe hypertension (OR=1.58 (1.04–2.32); P=0.027), arrhythmias (OR=4.93 (1.74–15.9); P=0.001), impaired fasting glucose/impaired glucose tolerance (OR=2.65 (1.70–4.13); P<0.0001), diabetes (OR=2.14 (1.34–3.40); P=0.0009), LVH (OR=11.9 (7.4–19.5); P<0.0001), diastolic (OR=3.32 (2.09–5.31); P<0.0001) and systolic dysfunction (OR=14.2 (6.95–32.2); P<0.0001), was higher in acromegaly. The most important predictor of LVH (t=2.4, P=0.02) and systolic dysfunction (t=−2.77, P=0.006) was disease duration and that of diastolic dysfunction was patient's age (t=−3.3, P=0.001). Patients with an estimated disease duration of >10 years had a relative risk to present cardiac complications three times higher than patients with estimated disease duration ≤5 years.ConclusionsThe prevalence of different features of cardiomyopathy is 3.3–14.2 times higher in the acromegalic than in the non-acromegalic population. The major determinant of cardiomyopathy is disease duration.
Menopause is a natural event occurring in a woman's life that is often accompanied by symptoms that might affect the quality of life. Diet has been shown to influence menopausal-related symptoms. ...Therefore, the present study aimed to investigate whether the adherence to the Mediterranean Diet (MD) might influence menopausal symptoms in women with obesity. This cross-sectional study involved postmenopausal women with obesity. Anthropometric and clinical parameters, and lifestyle habits were evaluated. All participants underwent interview questionnaires to assess: the adherence to the MD (PREDI PREvencion con DIetaMEDiterranea, PREDIMED), sleep quality (Pittsburgh Sleep Quality Index, PSQI), and severity of menopausal symptoms (Menopausal Rating Scale, MRS). One hundred postmenopausal women were enrolled (age 57.1 ± 7.3 years, BMI 35.0 ± 5.5 kg/m
). The mean PREDIMED score was 7.82 ± 1.66 showing moderate adherence to MD. Women in the marked MRS class had a significantly lower PREDIMED score than the none-to-moderate MRS class (p=0.036). The intake of legumes was associated with a lower MRS class (r= -0.201, p=0.045). In addition, the intake of extra-virgin olive oil inversely correlated with psychological symptoms (r= -0.230 p=0.021). Finally, 79% of participants were poor sleepers (mean PSQI score was 8.68 ± 3.6) and women in the severe MRS class had a worse sleep quality compared to other MRS classes. Post-menopausal women with marked menopausal symptoms had low adherence to MD. Legume consumption was associated with lower menopausal symptoms severity while extra virgin olive oil consumption was associated with lower psychological symptoms.
Pituitary neuroendocrine tumors (PitNET) are commonly benign tumors accounting for 10-25% of intracranial tumors. Prolactin-secreting adenomas represent the most predominant type of all PitNET and ...for this subtype of tumors, the medical therapy relies on the use of dopamine agonists (DAs). DAs yield an excellent therapeutic response in reducing tumor size and hormonal secretion targeting the dopamine receptor type 2 (D2DR) whose higher expression in prolactin-secreting adenomas compared to other PitNET is now well established. Moreover, although DAs therapy does not represent the first-line therapy for other PitNET, off-label use of DAs is considered in PitNET expressing D2DR. Nevertheless, DAs primary or secondary resistance, occurring in a subset of patients, may involve several molecular mechanisms, presently not fully elucidated. Dopamine receptors (DRs) expression is a prerequisite for a proper DA function in PitNET and several molecular events may negatively modify DR membrane expression, through the DRs down-regulation and intracellular trafficking, and DR signal transduction pathway. The current mini-review will summarise the presently known molecular events that underpin the unsuccessful therapy with DAs.
Several multi-kinase inhibitors were widely tested as potential first-line or second-line therapy in patients with advanced hepatocellular carcinoma (HCC). However, acquired drug resistance limits ...their clinical efficacy. Exosomes are microvesicles secreted by tumor and stromal cells that participate in many biological processes, including drug resistance. The current study evaluated the capability of exosomes derived from everolimus (EVE)-resistant HCC cells in inducing drug resistance in parental human HCC cells and the effect of 1,25(OH)
Vitamin D (VitD) treatment in restoring EVE sensitivity. The internalization of exosomes from EVE-resistant (EveR) cells into parental cells conferred the transmission of aggressive phenotype by promoting the transition of epithelial-to-mesenchymal phenotype, as demonstrated by immunofluorescence, and the acquisition of EVE resistance, as demonstrated by cell proliferation and colony formation assays. Moreover, the internalization of exosomes from EveR into parental cells induced deregulation of the mTOR pathway mainly by triggering the activation of the serine/threonine protein kinase Akt, involved in the cellular survival pathway, as demonstrated by Western blot analysis. Interestingly, the treatment with VitD prevented exosome-induced EVE resistance in HCC cells, significantly inhibiting cell proliferation but also partially reducing colony and size number when combined with EVE compared with control. In conclusion, the results of the current study demonstrated that exosomes derived from EveR cells could induce EVE resistance in EVE-sensitive HCC cells and that VitD can revert the exosome-induced EVE resistance by resensitizing to EVE treatment.
Despite the myocardial prolactin (PRL) binding activity and the known effect of enhancing contractility in the isolated rat heart, little information is available concerning the cardiovascular ...consequences of hyperprolactinemia in humans. To elucidate the effects of chronic hyperprolactinemia on cardiac structure and function, twenty-four patients with isolated PRL-secreting adenoma and twenty-four controls underwent a complete mono- and two-dimensional Doppler-echocardiography. Blood pressure and heart rate were similar in the two groups, and no significant differences were observed as to left ventricular (LV) geometry between patients and controls. Resting LV systolic function was normal in patients with hyperprolactinemia, as shown by similar values of fractional shortening and cardiac output. Conversely, hyperprolactinemic patients exhibited a slight impairment of LV diastolic filling, as demonstrated by the prolongation of the isovolumetric relaxation time and the increase of the atrial filling wave of mitral Doppler velocimetry (58 ± 13 vs. 47 ± 8 cm/s,
< 0.05) with a subgroup of females (16%) having a clear diastolic dysfunction, and a worse exercise capacity (6 min walking test 452 ± 70 vs. 524 ± 56;
< 0.05). In conclusion, hyperprolactinemia in humans may be associated with a slight impairment of diastolic function, with an overt diastolic dysfunction in a subgroup of females which correlated with poorer exercise performance, in the absence of significant abnormalities of LV structure and systolic function.
Prolactin effects on the pathogenesis of diabetes mellitus Scairati, Roberta; Auriemma, Renata Simona; Del Vecchio, Guendalina ...
European journal of clinical investigation,
June 2024, 2024-Jun, 2024-06-00, 20240601, Letnik:
54, Številka:
6
Journal Article
Recenzirano
Background
Prolactin (PRL) is a pituitary hormone promoting lactation in response to the suckling reflex. Beyond its well‐known effects, novel tissue‐specific and metabolic functions of PRL are ...emerging.
Aims
To dissect PRL as a critical mediator of whole‐body gluco‐insulinemic sensitivity.
Methods
PubMed‐based search with the following terms ‘prolactin’, ‘glucose metabolism’, ‘type 2 diabetes mellitus’, ‘type 1 diabetes mellitus’, ‘gestational diabetes mellitus’ was performed.
Discussion
The identification of the PRL‐glucose metabolism network poses the basis for unprecedented avenues of research in the pathogenesis of diabetes mellitus type 1 or 2, as well as of gestational diabetes. In this regard, it is of timely relevance to define properly the homeostatic PRL serum levels since glucose metabolism could be influenced by the circulating amount of the hormone.
Results
This review underscores the basic mechanisms of regulation of pancreatic β‐cell functions by PRL and provides a revision of articles which have investigated the connection between PRL unbalancing and diabetes mellitus. Future studies are needed to elucidate the burden and the role of PRL in the regulation of glucose metabolism and determine the specific PRL threshold that may impact the management of diabetes.
Conclusion
A careful evaluation and context‐driven interpretation of PRL levels (e.g., pregnancy, PRL‐secreting pituitary adenomas, drug‐related hyper‐ and hypoprolactinemia) could be critical for the correct screening and management of glucometabolic disorders, such as type 1 or 2 as well as gestational diabetes mellitus.
Prolactin (PRL) is promoted as critical mediator in glucose‐insulinemic metabolism through its receptor (PRL‐R) on pancreatic β‐cells. The early recognition of the pleiotropic roles of PRL opens avenues for diabetes research, especially in type 1 or 2 and gestational diabetes. It is of timely relevance to define homeostatic metabolic PRL levels, as it may influence glucose metabolism. This study aims to explore the regulation of pancreatic β‐cell by PRL and the interaction between PRL levels imbalance and diabetes mellitus.
Objective Acromegaly is associated with somatic disfigurements which impair self-perception of well-being and quality of life. Nowadays, limited data are available on the interplay between hormonal ...excess and psychological discomfort. The study aimed at investigating the psychological profile, sleep quality, sexual function, cognitive functions, and quality of life in patients with acromegaly. Methods In 223 acromegaly patients from 5 referral centres, global psychological profile, sleep quality, sexual function, cognitive function, and quality of life were investigated. Results Depression was found in ~30% of patients, and anxiety in two-thirds, together with severe discomfort in body image mainly in women. Obstructive sleep apnoea syndrome risk and sleep disorders were found in >50% of patients and daily sleepiness in ~20%. Sexual dysfunction was reported in most of the patients, with the most severe impairment in women. Cognitive functions were compromised in ~10% of cases. Disease duration and patient’s age and gender were the main determinants of these psychopathological conditions. Depression (P = 0.047), somatic-affective mood lowering (P = 0.021), state (P < 0.001) and trait (P = 0.013) anxiety, and body image distortion in body uneasiness test A (P < 0.001) and B (P = 0.006) were significantly worsened in patients <45 years and slightly worsened in those with disease duration less than 2 years. Male (P < 0.001) and female (P < 0.001) sexual function scores were significantly worsened in patients aged >64 years and slightly worsened in those with disease duration for more than 10 years, particularly in presence of cardiometabolic and respiratory complications. Cognitive symptoms were slightly worsened in older patients and in those with long disease duration. Conclusions Acromegaly is associated with a relevant impairment of psychological profile persisting despite remission and long-term medical treatment.
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