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Reviews in Endocrine & Metabolic... Jul 2024Prolactin (PRL) is primarily produced by the pituitary lactotrophic cells and while initially named for its role in lactation, PRL has several other biological roles... (Review)
Review
Prolactin (PRL) is primarily produced by the pituitary lactotrophic cells and while initially named for its role in lactation, PRL has several other biological roles including immunomodulation, osmotic balance, angiogenesis, calcium metabolism, and appetite regulation. Most of the PRL-related literature has traditionally focused on hyperprolactinemia, whereas hypoprolactinemia has received little attention. There is evidence to suggest that PRL receptors are widely distributed within the central nervous system including the limbic system. Furthermore, PRL has been shown to play key role in the stress regulation pathway. Recent data also suggest that hypoprolactinemia may be associated with increased sexual dysfunction, anxiety, and depression. In this paper we discuss the current understanding regarding the neuropsychological impact of hypoprolactinemia and highlight the need for adequately defining hypoprolactinemia as an entity and consideration for future replacement therapies.
PubMed: 38955985
DOI: 10.1007/s11154-024-09892-y -
JPMA. the Journal of the Pakistan... Jun 2024To evaluate serum prolactin and macroprolactin levels in patients on long-term proton pump inhibitors therapy.
OBJECTIVES
To evaluate serum prolactin and macroprolactin levels in patients on long-term proton pump inhibitors therapy.
METHODS
The cross-sectional study was conducted from January 2018 to November 2019 after approval from the ethics review committee of the Commission on Science and Technology for Sustainable Development in the South University, Abbottabad, Pakistan. The study included patients from two gastroenterology outpatient clinics in the Khyber Pakhtunkhwa province using proton pump inhibitors for ≥3 months either alone or in combination with either histamine receptor antagonists or prokinetics. Blood samples were collected from each patient for hormonal screening. Data was analysed using SPSS 25.
RESULTS
Of the 166 patients, 101(60.8%) were females and 65(39.2%) were males. The overall mean age was 42.5±14.2 years, and the median serum prolactin level was 23.2ng/ml (interquartile range: 14.0-38.0ng/ml). There were 96(58%) patients with normoprolactinaemia and 70(42%) with hypreprolactinaemia. There were 19(11.4%) patients using combination therapy, while the rest were on proton pump inhibitors monotherapy. There was a significant increase in serum prolactin level with combination therapy compared to monotherapy (p=0.001). Patients having treatment duration 11-20 months (p=0.006) and >40 months (p=0.001) were at high risk of developing hyperprolactinaemia.
CONCLUSIONS
Long-term use of proton pump inhibitors could increase serum prolactin levels, and appropriate evaluation is essential for clinical management.
Topics: Humans; Proton Pump Inhibitors; Female; Cross-Sectional Studies; Male; Hyperprolactinemia; Prolactin; Adult; Middle Aged; Pakistan; Prevalence
PubMed: 38948973
DOI: 10.47391/JPMA.9541 -
Sichuan Da Xue Xue Bao. Yi Xue Ban =... May 2024Recurrent pregnancy loss (RPL) presents a formidable challenge for individuals undergoing fertilization-embryo transfer (IVF-ET), forming both a clinical dilemma and a...
OBJECTIVE
Recurrent pregnancy loss (RPL) presents a formidable challenge for individuals undergoing fertilization-embryo transfer (IVF-ET), forming both a clinical dilemma and a focal point for scientific inquiry. This study endeavors to investigate the intricate interplay between clinical features, such as age, body mass index (BMI), and waist-to-hip ratio (WHR), and routine laboratory parameters, including sex hormones, blood composition, liver and thyroid functions, thyroid antibodies, and coagulation indicators, in RPL patients undergoing IVF-ET. By meticulously analyzing these variables, we aim to uncover the latent risk factors predisposing individuals to RPL. Identifying potential factors such as advanced maternal age, obesity, and insulin resistance will provide clinicians with vital insights and empirical evidence to strengthen preventive strategies aimed at reducing miscarriage recurrence.
METHODS
This retrospective case-controlled study included RPL patients who underwent IVF-ET treatment at Sun Yat-sen Memorial Hospital, Sun Yat-sen University, between January 2012 and March 2021 as the case cohort, compared with women receiving assisted reproductive treatment due to male infertility as the control cohort. The fasting peripheral blood was collected 5 days before the first menstrual cycle at least 12 weeks after the last abortion. The clinical characteristics and relevant laboratory indexes of the two groups were compared. Employing both univariate and multivariate logistic regression analyses, we sought to unearth potential high-risk factors underlying RPL. Additionally, a linear trend analysis was conducted to assess the linear relationship between total testosterone (TT) levels and the number of miscarriages.
RESULTS
In contrast to the control cohort, the RPL cohort exhibited significant increases in age, BMI, and WHR (<0.05). Notably, TT levels were markedly lower in the RPL cohort (=0.022), while no significant differences were observed between the two groups concerning basal follicle-stimulating hormone, luteinizing hormone, estradiol, progesterone, prolactin levels, and anti-Müllerian hormone levels (>0.05). Moreover, fasting insulin (FINS) levels and HOMA-IR index were notably elevated in the RPL cohort relative to the control cohort (<0.001), although no significant differences were observed in fasting blood glucose levels (>0.05). Furthermore, the neutrophil (NEU) count and NEU-to-lymphocyte ratio were notably higher in the RPL cohort (<0.01). Univariate logistic regression analysis identified several factors, including age≥35 years old, BMI≥25 kg/m, WHR>0.8, FINS>10 mU/L, HOMA-IR>2.14, NEU count>6.3×10 L, and an elevated NEU/lymphocyte ratio (NLR), as significantly increasing the risk of RPL (<0.05). Although TT levels were within the normal range for both cohorts, higher TT levels were associated with a diminished RPL risk (odds ratio [OR]=0.67, 95% confidence interval [CI]: 0.510-0.890, =0.005). After adjustments for confounding factors, age≥35 years old (OR=1.91, 95% CI: 1.06-3.43), WHR>0.8 (OR=2.30, 95% CI: 1.26-4.19), and FINS>10 mU/L (OR=4.50, 95% CI: 1.30-15.56) emerged as potent risk factors for RPL (<0.05). Conversely, higher TT levels were associated with a reduced RPL risk (OR=0.59, 95% CI: 0.38-0.93, =0.023). Furthermore, the linear trend analysis unveiled a discernible linear association between TT levels and the number of miscarriages ( =0.003), indicating a declining trend in TT levels with escalating miscarriage occurrences.
CONCLUSION
In patients undergoing IVF-ET, advanced maternal age, lower TT levels, increased WHR, and elevated FINS levels emerged as potent risk factors for RPL. These findings provide clinicians with valuable insights and facilitate the identification of patients who are at high risks and the formulation of preventive strategies to reduce the recurrence of miscarriages.
Topics: Humans; Female; Fertilization in Vitro; Abortion, Habitual; Embryo Transfer; Risk Factors; Retrospective Studies; Pregnancy; Case-Control Studies; Adult; Body Mass Index; Insulin Resistance; Obesity; Maternal Age; Male
PubMed: 38948280
DOI: 10.12182/20240560102 -
Sichuan Da Xue Xue Bao. Yi Xue Ban =... May 2024Based on the secreted frizzled-related protein 2 (SFRP2)-Wnt/β-catenin signaling pathway, this study explored the effect and mechanism of Cuiru Keli (CRKL) in the...
OBJECTIVE
Based on the secreted frizzled-related protein 2 (SFRP2)-Wnt/β-catenin signaling pathway, this study explored the effect and mechanism of Cuiru Keli (CRKL) in the treatment of postpartum hypogalactia.
METHODS
A rat model of postpartum hypogalactia was established by gavaging 2 mL of 1.6 mg/mL bromocriptine mesylate to female rats on the third day after delivery. Female rats with a delivery time difference of less than 48 hours were selected and randomly assigned to 7 groups, including a normal group (without any modeling or medication), a model group, a CRKL low-dose group of model group model rats receiving CRKL at the dose of 3 g/kg, a CRKL medium-dose group of model rats receiving CRKL at the dose of 6 g/kg, a CRKL high-dose group of model rats receiving CRKL at the dose of 9 g/kg, a positive drug group of model rats receiving domperidone at the dose of 3 mg/kg, and a negative control (NC) group of model rats receiving normal saline. Each group contained 6 rats. Except for the normal and model groups, the remaining 5 groups were continuously administered with the respective intervention drugs at the specified doses by gavage once a day for 10 days. Changes in the total litter mass of the offspring in the 7 groups within 10 days were measured, and HE staining was performed to identify pathological changes in the mammary tissue (MT). Six groups of rats (excluding the positive control group) were used to observe the pathological changes of eosinophils in pituitary tissue. ELISA was performed to determine the content of prolactin (PRL) in serum, immunohistochemical staining was used to determine the expression of prolactin receptor (PRLR) in MT, and RT-qPCR was used to determine the mRNA expression of genes related to lactation in MT. Network pharmacology and molecular docking were used to study the therapeutic effect and mechanism of CRKL on postpartum hypogalactia, particularly whether it acted through the SFRP2-Wnt/β-catenin signaling pathway. The mechanism of CRKL treatment was further validated by detecting mRNA (RT-qPCR) and protein expression (Western blot) of related pathway genes. Cell experiments were conducted using primary culture rat mammary epithelial cells (RMEC) from rat MT. RMEC were divided into four groups, including a normal group (primary culture RMEC, untreated), overexpression group (primary cultured RMEC treated with overexpression vector), overexpression+CRKL group (receiving treatment for overexpression group plus 10% drug-containing serum), and negative control group (primary culture RMEC treated with empty vector). The effect of CRKL on the expression of lactation-related genes , , and mRNA after overexpression was detected by RT-qPCR.
RESULTS
In this study, CRKL was administered at a dose of 3 g/kg in the CRKL low-dose group, 6 g/kg in the medium-dose group, and 9 g/kg in the high-dose group (<0.05 or <0.01). Compared with the model group, CRKL at all doses significantly increased the total litter weight gain of the offsprings within 10 days (<0.05 or <0.01), and effectively increased lactation (<0.01), the area of mammary lobules, and the size and filling of acinar cavities. CRKL at all doses also increased the number of eosinophils that secreted PRL in the pituitary gland of the postpartum hypogalactia rat model, and increased the content of PRL in the serum (<0.05 or <0.01). CRKL promoted the secretion and expression of PRL in postpartum hypogalactic model rats. In addition, it significantly promoted the expression of genes related to milk fat, milk protein, and lactose synthesis in MT (<0.05 or <0.01). Network pharmacology predicted that the Wnt signaling pathway might be a key pathway for CRKL in treating postpartum hypogalactia. The molecular docking results showed that related chemical components in CRKL had good binding ability with CCND1 and SFRP2. Compared with the model group, CRKL at all doses inhibited the expression of gene (<0.01) and activated the mRNA and protein expression of CCND1 and c-Myc in the Wnt/β-catenin signaling pathway in MT (<0.05 or <0.01). Cell experiments showed that, compared to the normal group, overexpression reduced the mRNA expression of milk synthesis-related genes , , and in RMEC (<0.01). The CCK8 results indicated that 10% of the drug-containing serum was the effective concentration administered to cells (<0.01). After administering drug-containing serum, the expression of the lactation-related genes , , and were up-regulated (compared with the overexpression group, <0.01).
CONCLUSION
CRKL alleviates postpartum hypogalactia through the SFRP2-Wnt/β-catenin signaling pathway. SFRP2 might be a potential new target for the diagnosis and treatment of postpartum hypogalactia. This reveals a new mechanism of CRKL in treating postpartum hypogalactia and promotes its clinical application.
Topics: Animals; Female; Rats; Wnt Signaling Pathway; Drugs, Chinese Herbal; Postpartum Period; Rats, Sprague-Dawley; Pregnancy; beta Catenin
PubMed: 38948275
DOI: 10.12182/20240560201 -
Brain Research Jun 2024Prolactin has been recognized as neuroprotective hormone against various types of neuronal damage. This study was aimed to determine if prolactin protects against...
Prolactin has been recognized as neuroprotective hormone against various types of neuronal damage. This study was aimed to determine if prolactin protects against streptozotocin injury. A series of experiments were performed to determine neuronal survival by counting total neurons in medial hippocampus cortex and cerebellum. Astrogliosis was determined by immunofluorescence assays using GFAP, and behavioral improvement by prolactin after neuronal damage was determined by open-field and light-dark box tests. Results demonstrated that prolactin induced significant neuronal survival in both the hippocampus and cortex, but not in the cerebellum. No increase in astrogliosis was identified, but a significant reduction in anxiety levels was observed. Overall data indicate that prolactin may protect against a complex form of cell damage including oxidant stress and metabolic disruption by streptozotocin. Prolactin may be helpful strategy in the treatment of neuronal damage in neurological diseases.
PubMed: 38945469
DOI: 10.1016/j.brainres.2024.149104 -
Steroids Jun 2024Anabolic-androgenic steroids (AAS) are used widely, but in illegal ways mostly by young men as performance-enhancing and image-enhancing drugs (IPED). long-term usage of...
Anabolic-androgenic steroids (AAS) are used widely, but in illegal ways mostly by young men as performance-enhancing and image-enhancing drugs (IPED). long-term usage of AAS, usually in conjunction with other illegal substances, can have extremely detrimental impacts on the reproductive system. The primary goal of this study was to examine any possible detrimental effects of AAS on sex hormone levels, a liver and kidney function in individuals who frequent fitness centers in Iraq-Baghdad. In this research, there are 60 participants (20-37 years old); 30 athletes who visited the different gyms in Baghdad/ Iraq and used AAS such as testosterone, Boldenone, Cybontae, Deca Durabellin; and 30 athletes who did not take any synthetics hormones and serve as control. All participants answered the questionnaire form which included their age, the type of used AAS, when they started to take it, and the total usage number per week. The blood (5 ml) was drawn from every participant to separate the serum. The serum was used to measure some hormones (Testosterone, FSH, LH, prolactin and Estrodiol) and liver and kidney function parameters. The results showed a significantly lower level of testosterone and FSH in the AAS-users' bodybuilding group compared to the control group. In comparison with the control group, there was a notable rise in the PRL level in the serum of AA users. However, when comparing the serum levels of LH and Estrodiol in the AAS-user group to those in the control group, no discernible variations were seen. AAS users had a significantly higher level of ALT and lower ALP than controls, although there is no difference in AST levels between the two groups. The creatine level was significantly higher in the AAS-user compared to the control group, but not urea. In conclusion, the effects of AAS and other supplements on sex hormones and kidney, liver function, and vary depending on how long they are used, with the effects of AAS being more pronounced. Therefore, there is a need for culturally sensitive measures to prevent steroid abuse among youth.
PubMed: 38945388
DOI: 10.1016/j.steroids.2024.109465 -
Journal of Dairy Science Jun 2024The uptake of AA in mammary tissues is affected by prolactin (PRL). To investigate whether PRL-induced AA uptake is involved in L-type AA transporter 1 (LAT1), we...
The uptake of AA in mammary tissues is affected by prolactin (PRL). To investigate whether PRL-induced AA uptake is involved in L-type AA transporter 1 (LAT1), we analyzed the changes of AA in the medium of dairy cow mammary epithelial cells in the presence of PRL or PRL plus BCH, an inhibitor of LAT1. Then Western blot and luciferase assay were used to detect the regulation mechanism of PRL on LAT1 expression and function. Our results showed that Thr, Val, Met, Ile, Leu, Tyr, Lys, Phe, and His are LAT1 substrates and could be transported into mammary epithelial cells via LAT1. PRL stimulation increased the uptake of most AA into mammary epithelial cells of dairy cows, however, inhibition of LAT1 transport activity reduced PRL-induced AA uptake, suggesting that the effect of PRL on AA transport depends on LAT1 expression and function. PRL stimulation upregulated LAT1 expression and plasma membrane location not only in dairy cow mammary epithelial cells, but also in mouse mammary epithelial cell line HC11. Western blot showed that PI3K-AKT-mTOR signaling could be activated in PRL-stimulated mammary epithelial cells. Treatment of cells with LY294002 decreased PI3K-AKT-mTOR activation, as well LAT1 expression, that in turn decreased milk protein synthesis. Luciferase assay showed PRL treatment increased the promoter activity of LAT1 promoter fragment -419∼-86 bp. Treatment of cells with LY294002, an inhibitor of PI3K, or SC79, an activator of AKT abolished or promoted the transcriptional activity of this promoter fragment in the presence of PRL. These results suggested that the -419∼-86 bp fragment of LAT1 promoter mediates the action of PI3K-AKT-mTOR signaling on LAT1 transcription in mammary epithelial cells of dairy cows, which in turn increased LAT1 expression and AA uptake.
PubMed: 38945262
DOI: 10.3168/jds.2024-24746 -
European Journal of Obstetrics,... Jun 2024Isntroduction. Polycystic ovary syndrome (PCOS) is a multifaceted endocrine-gynecological condition affecting a substantial number of women during their reproductive... (Review)
Review
Comparative efficacy of metformin combined with cabergoline versus metformin alone in patients with PCOS and hyperprolactinemia: A systematic review and meta-analysis of randomized controlled trials.
UNLABELLED
Isntroduction. Polycystic ovary syndrome (PCOS) is a multifaceted endocrine-gynecological condition affecting a substantial number of women during their reproductive years. Metformin (MET) has been shown to improve ovarian function in PCOS-related conditions, while cabergoline is recognized for its powerful and sustained ability to reduce prolactin levels. This study investigates the potential impact of combining cabergoline with metformin while comparing it with metformin alone in the treatment of PCOS alongside hyperprolactinemia.
METHOD
To gather data, we searched PubMed, Google Scholar, ScienceDirect, and Cochrane Central. Eligible studies were randomized controlled trials involving patients with PCOS and hyperprolactinemia. Outcome measures included changes in the levels of prolactin, testosterone, DHEAS, BMI and menstrual irregularities. RevMan version 5.4 was used to analyze outcomes.
RESULT
This study incorporated three Randomized Controlled Trials (RCTs) involving 405 participants in total. Patients receiving a combination of metformin and cabergoline experienced significant reductions in prolactin and testosterone levels (p= <0.0001 and p=<0.0001, respectively). Conversely, alterations in DHEAS levels and BMI did not reach statistical significance (p = 0.19 and p = 0.71, respectively). Notably, women solely prescribed metformin exhibited significantly higher rates of menstrual irregularities compared to those receiving both metformin and cabergoline (p=<0.0001).
CONCLUSION
Our analysis underscores the synergistic effect achieved by pairing metformin and cabergoline in patients with PCOS and hyperprolactinemia. However, we encountered only a restricted number of studies meeting our criteria. It is imperative to consistently assess the combined effects of metformin and cabergoline to gain deeper insights into their effectiveness in addressing PCOS and hyperprolactinemia.
PubMed: 38945085
DOI: 10.1016/j.ejogrb.2024.06.037 -
Schizophrenia Research Jun 2024Certain antipsychotics elevate prolactin levels in patients with schizophrenia spectrum disorders (SSD), potentially affecting cognition, symptoms, and hormone levels....
BACKGROUND
Certain antipsychotics elevate prolactin levels in patients with schizophrenia spectrum disorders (SSD), potentially affecting cognition, symptoms, and hormone levels. This study examines the association between prolactin, testosterone, and estrogen and cognition and symptoms in men with SSD, considering antipsychotic medication.
METHODS
This cross-sectional study included 128 men with SSD and 44 healthy men from two trials. Patients were divided into a prolactin-sparing (n = 53) and prolactin-raising group (n = 75) based on antipsychotic medication. We examined the association between hormones (testosterone, estrogen and prolactin), and cognition and symptoms using backward linear regression. Three domains of cognition were assessed including: processing speed, verbal fluency, and working memory, while symptoms were measured using the Positive and Negative Syndrome Scale (PANSS).
RESULTS
Prolactin levels were highest in the prolactin-raising group, followed by the control group, and lowest in the prolactin-sparing group (H = 45.279, p < .001). Testosterone and estrogen levels did not differ significantly between groups. In the prolactin-raising group, prolactin negatively correlated with testosterone (r(73) = -0.32, p = .005). Higher testosterone predicted better cognitive functioning (working memory: β = 0.20, p = .007, verbal fluency: β = 0.30, p = .001) and lower symptom scores (total: β = -0.21, p = .001; negative: β = -0.24, p = .002) in men with SSD. Conversely, higher estrogen levels related to slower processing speed (β = -0.22, p < .001) and higher symptoms scores (β = 0.23, p = .010) in men with SSD.
CONCLUSION
The results suggest positive associations between testosterone and cognition and symptoms in men with SSD, while suggesting that high prolactin levels could relate to lower testosterone levels, possibly worsening cognition and symptoms in men with SSD.
PubMed: 38944973
DOI: 10.1016/j.schres.2024.06.022 -
General and Comparative Endocrinology Jun 2024Parental care is regulated by multiple endocrine mechanisms. Among these hormones, prolactin (PRL) is involved in the expression of parental behaviors. Despite the... (Review)
Review
Parental care is regulated by multiple endocrine mechanisms. Among these hormones, prolactin (PRL) is involved in the expression of parental behaviors. Despite the consensus that PRL mediates variation in parental effort with age and body condition, its role in the adjustment of parental effort to fluctuating environmental conditions, including changing predation pressure, still awaits further investigation. To shed light on this knowledge gap, we relied on a long-term monitoring of female common eiders Somateria mollissima (n = 1277 breeding attempts, 2012-2022) incubating under fluctuating predation risk to investigate the link between baseline PRL levels and female minimum age, body condition, clutch size, environmental parameters (predation pressure, climate, nest microhabitat) and hatching success. We predicted that PRL would be higher in older females, those in better condition or incubating larger clutches. We also predicted that females would reduce parental effort when nesting under challenging environmental conditions (high predation pressure or poor climatic conditions), translated into reduced baseline PRL levels. We also explored how variation in PRL levels, female characteristics and environmental parameters were related to hatching success. Following our predictions, PRL levels were positively associated with body condition and female age (before showing a senescent decline in the oldest breeders). However, we did not observe any population-level or individual-level reduction in PRL levels in response to increasing predation pressure. Population-level baseline PRL levels instead increased over the study period, coincident with rising predation threat, but also increasing female body condition and age. While we did not provide evidence for a direct association between baseline PRL levels and predation risk, our results support the idea that elevated baseline PRL levels promote hatching success under internal constraints (in young, inexperienced, breeders or those incubating a large clutch) or constraining environmental conditions (during years of high predation pressure or poor climatic and foraging conditions). Finally, the low repeatability of baseline PRL levels and high interannual variability highlight considerable within-individual flexibility in baseline PRL levels. Further research should explore flexibility in parental effort to changing environmental conditions, focusing on both baseline and stress-induced PRL levels.
PubMed: 38936675
DOI: 10.1016/j.ygcen.2024.114574