RESUMEN

BACKGROUND: In the context of rheumatoid arthritis and its systemic inflammatory implications, there is an increasing interest in investigating the role of prolactin in the clinical and metabolic aspects of the disease. This study aimed to explore the potential links between serum prolactin levels, serum glucose levels, and the clinical manifestations of arthritis. METHODS: This exploratory, cross-sectional, observational study focused on women diagnosed with rheumatoid arthritis. The research involved assessing prolactin and blood glucose concentrations, alongside specific clinical traits such as disease-related inflammation, morning stiffness, and fatigue intensity. The presence of changes in serum prolactin (PRL) was initially compared among the groups based on disease activity intensity. Using a multinomial regression analysis, the study analyzed the impact of predetermined clinical and metabolic factors on various categories of prolactin concentration. RESULTS: Out of the 72 participants included in the study, hyperprolactinemia was detected in 9.1% of the sample. No differences in serum PRL were identified among the evaluated groups based on disease activity. Following multivariate analysis, no statistically significant differences were identified for the outcomes of inflammatory activity and morning stiffness within each PRL category when compared to the reference category for PRL. There was no increased likelihood of encountering blood glucose levels below 100 mg/dl among individuals with higher prolactin concentrations compared to those in the lowest prolactin category (OR 5.43, 95% CI 0.51-58.28). The presence of clinically significant fatigue revealed a higher likelihood of encountering this outcome among patients with intermediate PRL values (prolactin categories 7.76-10.35 with OR 5.18, 95% CI 1.01-26.38 and 10.36-15.29 with OR 6.25, 95% CI 1.2-32.51) when compared to the reference category. CONCLUSIONS: The study found no discernible correlation between prolactin concentrations and worse scores for inflammatory activity of the disease, nor between prolactin concentrations and serum glucose levels. The findings regarding fatigue should be approached with caution given the exploratory nature of this study.

Asunto(s)

Artritis Reumatoide , Glucemia , Hiperprolactinemia , Prolactina , Humanos , Prolactina/sangre , Artritis Reumatoide/sangre , Femenino , Estudios Transversales , Glucemia/análisis , Persona de Mediana Edad , Hiperprolactinemia/sangre , Adulto , Índice de Severidad de la Enfermedad , Fatiga/sangre , Fatiga/etiología

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Toxoplasmosis is an infection caused by the parasite Toxoplasma gondii. One-third of the world's population has come into contact with this parasite. In Mexico, the prevalence is between 15% and 50% in the general population and 34.9% in women with high-risk pregnancies. In pregnancy, the highest incidence of infection occurs in the third trimester and fetal damage is inversely proportional to gestational age. Maternal hormones play a fundamental role in the immune response. There are very few studies, with controversial results, on the levels of increased hormones and their relationship to the kinetics of T. gondii infections during pregnancy. The aim was to determine the serum levels of 17-ß estradiol, prolactin, and progesterone, and their association with anti-T. gondii antibodies' kinetics in pregnancy. Fifty-two pregnant patients were studied. A questionnaire with sociodemographic and clinical aspects was used. Afterward, 10 mL of venous blood was collected by venipuncture every trimester. The concentrations of 17-ß estradiol, progesterone, and prolactin were measured, using the ELISA method. In addition, anti-Toxoplasma IgG and IgM antibodies were also determined in the first, second, and third trimester. The prevalence of anti-Toxoplasma IgG antibodies was 26.92% in the first and second trimester and 32.7% in the third trimester. In seropositive women, 17-ß estradiol increased in the second and third trimesters of pregnancy. Progesterone increased significantly p < 0.039 in the third trimester in these women, while prolactin increased in the second trimester with a statistical significance of p < 0.021. In addition, 17-ß estradiol, progesterone, and prolactin are associated with T. gondii infection during pregnancy. New studies are necessary to clarify the specific mechanisms of immune response related to these hormones during pregnancy.

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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.

Asunto(s)

Hipocampo , Neuronas , Fármacos Neuroprotectores , Prolactina , Estreptozocina , Animales , Prolactina/metabolismo , Masculino , Fármacos Neuroprotectores/farmacología , Hipocampo/metabolismo , Hipocampo/efectos de los fármacos , Neuronas/metabolismo , Neuronas/efectos de los fármacos , Ratas , Neuroprotección/fisiología , Neuroprotección/efectos de los fármacos , Ratas Sprague-Dawley , Gliosis/metabolismo , Cerebelo/metabolismo , Cerebelo/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Encéfalo/metabolismo , Encéfalo/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/fisiología

RESUMEN

Ischemic stroke is a significant global health issue, ranking fifth among all causes of death and a leading cause of serious long-term disability. Ischemic stroke leads to severe outcomes, including permanent brain damage and neuronal dysfunction. Therefore, decreasing and preventing neuronal injuries caused by stroke has been the focus of therapeutic research. In recent years, many studies have shown that fluctuations in hormonal levels influence the prognosis of ischemic stroke. Thus, it is relevant to understand the role of hormones in the pathophysiological mechanisms of ischemic stroke for preventing and treating this health issue. Here, we investigate the contribution of the prolactin/vasoinhibin axis, an endocrine system regulating blood vessel growth, immune processes, and neuronal survival, to the pathophysiology of ischemic stroke. Male mice with brain overexpression of prolactin or vasoinhibin by adeno-associated virus (AAV) intracerebroventricular injection or lacking the prolactin receptor (Prlr-/-) were exposed to transient middle cerebral artery occlusion (tMCAO) for 45 min followed by 48 h of reperfusion. Overexpression of vasoinhibin or the absence of the prolactin receptor led to an increased lesion volume and decreased survival rates in mice following tMCAO, whereas overexpression of prolactin had no effect. In addition, astrocytic distribution in the penumbra was altered, glial fibrillary acidic protein and S100b mRNA expressions were reduced, and interleukin-6 mRNA expression increased in the ischemic hemisphere of mice overexpressing vasoinhibin. Of note, prolactin receptor-null mice (Prlr-/-) showed a marked increase in serum vasoinhibin levels. Furthermore, vasoinhibin decreased astrocyte numbers in mixed hippocampal neuron-glia cultures. These observations suggest that increased vasoinhibin levels may hinder astrocytes' protective reactivity. Overall, this study suggests the involvement of the prolactin/vasoinhibin axis in the pathophysiology of ischemic stroke-induced brain injury and provides insights into the impact of its dysregulation on astrocyte reactivity and lesion size. Understanding these mechanisms could help develop therapeutic interventions in ischemic stroke and other related neurological disorders.

Asunto(s)

Proteínas de Ciclo Celular , Gliosis , Prolactina , Receptores de Prolactina , Animales , Prolactina/metabolismo , Masculino , Ratones , Gliosis/patología , Gliosis/metabolismo , Receptores de Prolactina/metabolismo , Receptores de Prolactina/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Ratones Endogámicos C57BL , Astrocitos/metabolismo , Astrocitos/patología , Ratones Noqueados , Accidente Cerebrovascular Isquémico/metabolismo , Accidente Cerebrovascular Isquémico/patología , Infarto de la Arteria Cerebral Media/patología , Infarto de la Arteria Cerebral Media/metabolismo

RESUMEN

Dopamine agonists are the first line of treatment for patients with symptomatic hyperprolactinemia due to prolactinomas and in those with idiopathic hyperprolactinemia. Treatment with these agents is effective in 80%-90% of the cases. Infertility treatment of patients with hyperprolactinemia is also carried out with dopamine agonists, aiming for the normalization of prolactin levels. The risk of symptomatic growth of prolactinomas during pregnancy is dependent on the tumor's size, duration of previous treatments, and prolactin levels. Notably, the corresponding risk is relatively low in cases of microprolactinomas (<5%). Remission of hyperprolactinemia occurs in about 30% of the patients after drug treatment and may also occur after pregnancy and menopause. The use of some drugs, such as antidepressants and antipsychotics, is a frequent cause of hyperprolactinemia, and managing this occurrence involves unique considerations. This position statement by the Brazilian Federation of Gynecology and Obstetrics Associations (Febrasgo) and Brazilian Society of Endocrinology and Metabolism (SBEM) addresses the recommendations for measurement of serum prolactin levels and the investigations of symptomatic and asymptomatic hyperprolactinemia and drug-induced hyperprolactinemia in women.

Asunto(s)

Hiperprolactinemia , Neoplasias Hipofisarias , Prolactinoma , Embarazo , Humanos , Femenino , Hiperprolactinemia/tratamiento farmacológico , Prolactinoma/terapia , Agonistas de Dopamina/efectos adversos , Prolactina , Neoplasias Hipofisarias/terapia , Brasil

RESUMEN

BACKGROUND: Men with macroprolactinoma can present persistent hypogonadism despite normoprolactinemia achieved with clinical and/or neurosurgical treatment. Usually, testosterone replacement therapy is indicated. Nevertheless, although off-label, clomiphene citrate (CC), a selective estrogen receptor modulator, has also been used, mainly when fertility is an issue. The aim of this study is to evaluate the effectiveness of CC in recovering the gonadal axis in men with macroprolactinoma, with or without hyperprolactinemia, and evaluate its safety as a long-term therapy. METHODS: This is a retrospective study including 10 men with macroprolactinoma on cabergoline treatment and persistent hypogonadism. All patients received initially 50 mg/d of CC. RESULTS: The median age at diagnosis of prolactinomas was 34 (range, 26-60) years old. All patients were treated with cabergoline at a median maximum dose of 2 (1-7) mg/week, with a median time of treatment of 8.5 (2-15) years. Prolactin was still above the normal range when CC was introduced only in two patients. The mean duration of CC therapy was 3.2 (±2.8) years. Prolactin levels maintained stable (p = 0.252) and testosterone increased (p = 0.027) significantly on CC therapy. Tumor size remained stable. Eight patients (80%) maintained testosterone above 300 ng/dL and were classified as responders. Three responders succeeded in using a lower dose of CC and one of them completed withdrawal CC and maintained eugonadism. There were no side effects or safety concerns reported. CONCLUSION: CC should be seen as a safe treatment option for men with macroprolactinoma and persistent hypogonadism.

Asunto(s)

Cabergolina , Clomifeno , Hipogonadismo , Neoplasias Hipofisarias , Prolactinoma , Humanos , Masculino , Adulto , Prolactinoma/tratamiento farmacológico , Persona de Mediana Edad , Hipogonadismo/tratamiento farmacológico , Estudios Retrospectivos , Neoplasias Hipofisarias/tratamiento farmacológico , Cabergolina/uso terapéutico , Cabergolina/administración & dosificación , Clomifeno/uso terapéutico , Clomifeno/administración & dosificación , Resultado del Tratamiento , Testosterona/sangre , Moduladores Selectivos de los Receptores de Estrógeno/administración & dosificación , Moduladores Selectivos de los Receptores de Estrógeno/uso terapéutico , Ergolinas/uso terapéutico , Ergolinas/administración & dosificación , Prolactina/sangre

RESUMEN

Abstract Background: Hyperprolactinemia is increased in women with infertility and recurrent pregnancy loss; the prevalence of hyperprolactinemia in Mexican women with infertility is unknown. Objective: To know the prevalence of hyperprolactinemia and the clinical-biochemical characteristics in Mexican women with infertility. Methods: This cross-sectional study included infertile women attending in a third-level hospital. All women had prolactin determination and a complete hormonal profile. Women with TSH > 2.5 mlU/L or those taking dopaminergic drugs were excluded. The prevalence of hyperprolactinemia was calculated with a 95% confidence interval (95% CI). Results: A total of 869 women were included in the study. The prevalence of hyperprolactinemia was 9.6% (95% CI 7.7-11.7%). Of the 83 women with hyperprolactinemia, 52 (62.2%) had serum prolactin values between 25 and 40, 17 (20.4%) between 41 and 60, and 14 (16.8%) > 60 ng/m. The prevalence of one or more miscarriages in women with hyperprolactinemia versus those without hyperprolactinemia among women with secondary infertility was 19/20 (95%) versus 116/197 (58.9%), respectively, p = 0.002. The prevalence of anovulation and clinical hyperandrogenism was significantly higher in women without hyperprolactinemia. Conclusion: Hyperprolactinemia affects one of ten Mexican women with infertility. Women with hyperprolactinemia and secondary infertility showed a higher frequency of a history of one or more miscarriage.

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Resumen Antecedentes: La hiperprolactinemia se incrementa en mujeres con infertilidad y pérdida gestacional recurrente. Se desconoce la prevalencia de hiperprolactinemia en mujeres mexicanas con infertilidad. Objetivo: Conocer la prevalencia de hiperprolactinemia y las características clínico-bioquímicas en mujeres mexicanas con infertilidad. Método: Estudio transversal que incluyó a mujeres con infertilidad en un hospital de tercer nivel. Todas las mujeres tenían determinación de prolactina y perfil hormonal completo. Se excluyeron mujeres con hormona estimulante de la tiroides > 2.5 mUI/l o que tomaban medicamentos dopaminérgicos. Se calculó la prevalencia de hiperprolactinemia con intervalo de confianza al 95% (IC95%). Resultados: En total se incluyeron 869 mujeres. La prevalencia de hiperprolactinemia fue 9.6% (IC95%: 7.7-11.7%). De 83 mujeres con hiperprolactinemia, 52 (62.2%) tenían valores de prolactina entre 25-40, 17 (20.4%) entre 41-60 y 14 (16.8%) > 60 ng/ml. La prevalencia de uno o más abortos espontáneos en mujeres con hiperprolactinemia vs. sin hiperprolactinemia entre mujeres con infertilidad secundaria fue: 19/20 (95%) versus 116/197 (58.9%), respectivamente (p = 0.002). La prevalencia de anovulación e hiperandrogenismo clínico fue significativamente mayor en mujeres sin hiperprolactinemia. Conclusiones: La hiperprolactinemia afecta a una de cada diez mujeres mexicanas con infertilidad. Las mujeres con infertilidad secundaria e hiperprolactinemia mostraron mayor frecuencia de antecedente de uno o más abortos.

RESUMEN

Olfactory communication is triggered by pheromones that profoundly influence neuroendocrine responses to drive social interactions. Two principal olfactory systems process pheromones: the main and the vomeronasal or accessory system. Prolactin receptors are expressed in both systems suggesting a participation in the processing of olfactory information. We previously reported that prolactin participates in the sexual and olfactory bulb maturation of females. Therefore, we explored the expression of prolactin receptors within the olfactory bulb during sexual maturation and the direct responses of prolactin upon pheromonal exposure. Additionally, we assessed the behavioral response of adult females exposed to male sawdust after prolactin administration and the consequent activation of main and accessory olfactory bulb and their first central relays, the piriform cortex and the medial amygdala. Last, we investigated the intracellular pathway activated by prolactin within the olfactory bulb. Here, prolactin receptor expression remained constant during all maturation stages within the main olfactory bulb but decreased in adulthood in the accessory olfactory bulb. Behaviorally, females that received prolactin actively explored the male stimulus. An increased cFos activation in the amygdala and in the glomerular cells of the whole olfactory bulb was observed, but an augmented response in the mitral cells was only found within the main olfactory bulb after prolactin administration and the exposure to male stimulus. Interestingly, the ERK pathway was upregulated in the main olfactory bulb after exposure to a male stimulus. Overall, our results suggest that, in female mice, prolactin participates in the processing of chemosignals and behavioral responses by activating the main olfactory system and diminishing the classical vomeronasal response to pheromones.

Asunto(s)

Bulbo Olfatorio , Prolactina , Conducta Sexual Animal , Animales , Bulbo Olfatorio/efectos de los fármacos , Bulbo Olfatorio/metabolismo , Bulbo Olfatorio/fisiología , Femenino , Prolactina/metabolismo , Prolactina/farmacología , Ratones , Masculino , Conducta Sexual Animal/fisiología , Conducta Sexual Animal/efectos de los fármacos , Receptores de Prolactina/metabolismo , Maduración Sexual/fisiología , Conducta Social , Feromonas/farmacología , Amígdala del Cerebelo/efectos de los fármacos , Amígdala del Cerebelo/metabolismo

RESUMEN

Due to the current limited knowledge about the role of filamin A (FLNA) in pituitary tumour progression, we aimed to analyse FLNA expression levels and its impact on aggressive markers of pituitary neuroendocrine tumours (PitNETs), using an integrative approach of in vivo and in vitro models and human samples. An increase in the expression levels of FLNA was observed in the advanced tumoural stages of the hyperplastic adenomatous pituitary model, concomitant with a decrease in cell proliferation and with a modification in the subcellular localisation of this protein. Similarly, overexpression of FLNA in the somatolactotropic GH3 cell line induced a decrease in the cell proliferation, promoted a migratory phenotype, increased invasion activity, and decreased the prolactin secretion. Cyclin D1 (CCND1) and cyclin-dependent kinase 4 (CDK4) expression increased in both models in correlation with the increase observed in FLNA levels. When human tissues were analysed a significant increase of FLNA was observed in PitNETs compared to normal pituitary gland, with heterogeneous intracellular localisation. Higher levels of FLNA expression were observed in tumours with invasive characteristics. These results underline the crucial roles of FLNA as a modulator of pathological markers and as a potential prognostic marker in pituitary tumours.

Asunto(s)

Adenoma , Tumores Neuroendocrinos , Neoplasias Hipofisarias , Humanos , Neoplasias Hipofisarias/metabolismo , Filaminas/genética , Filaminas/metabolismo , Hipófisis/metabolismo

RESUMEN

ABSTRACT Dopamine agonists are the first line of treatment for patients with symptomatic hyperprolactinemia due to prolactinomas and in those with idiopathic hyperprolactinemia. Treatment with these agents is effective in 80%-90% of the cases. Infertility treatment of patients with hyperprolactinemia is also carried out with dopamine agonists, aiming for the normalization of prolactin levels. The risk of symptomatic growth of prolactinomas during pregnancy is dependent on the tumor's size, duration of previous treatments, and prolactin levels. Notably, the corresponding risk is relatively low in cases of microprolactinomas (<5%). Remission of hyperprolactinemia occurs in about 30% of the patients after drug treatment and may also occur after pregnancy and menopause. The use of some drugs, such as antidepressants and antipsychotics, is a frequent cause of hyperprolactinemia, and managing this occurrence involves unique considerations. This position statement by the Brazilian Federation of Gynecology and Obstetrics Associations (Febrasgo) and Brazilian Society of Endocrinology and Metabolism (SBEM) addresses the recommendations for measurement of serum prolactin levels and the investigations of symptomatic and asymptomatic hyperprolactinemia and drug-induced hyperprolactinemia in women.

RESUMEN

Serum prolactin (PRL) levels exhibit a gradual rise both in male and female rats from birth to adulthood, with females consistently displaying higher levels compared to age-matched males. This pattern has traditionally been attributed to the development and maturation of endocrine and neuroendocrine networks responsible for regulating PRL synthesis and secretion. However, the effect of dopamine (DA), which acts as an inhibitory factor on lactotroph function, also increases from birth to puberty, particularly in females. Nonetheless, the secretion of PRL remains higher in females compared to males. On the other hand, the observed sex differences in serum PRL levels during early postnatal development cannot be attributed to the influence of estradiol (E2). While serum E2 levels gradually increase after birth, only after 45 days of life do the disparities in E2 levels between females and males become evident. These observations collectively suggest that neither the maturation of hypothalamic DA regulation nor the rise in E2 levels can account for the progressive and sustained elevation in serum PRL levels and the observed sexual dimorphism during postnatal development. This review highlights the importance of recent discoveries in animal models that shed light on inhibitory mechanisms in the control of PRL secretion within the pituitary gland itself, that is intrapituitary mechanisms, with a specific emphasis on the role of transforming growth factor ß1 and activins in PRL secretion.

RESUMEN

BACKGROUND: The prairie vole (Microtus ochrogaster) is a socially monogamous rodent that establishes an enduring pair bond after cohabitation, with (6 h) or without (24 h) mating. Previously, we reported that social interaction and mating increased cell proliferation and differentiation to neuronal fate in neurogenic niches in male voles. We hypothesized that neurogenesis may be a neural plasticity mechanism involved in mating-induced pair bond formation. Here, we evaluated the differentiation potential of neural progenitor cells (NPCs) isolated from the subventricular zone (SVZ) of both female and male adult voles as a function of sociosexual experience. Animals were assigned to one of the following groups: (1) control (Co), sexually naive female and male voles that had no contact with another vole of the opposite sex; (2) social exposure (SE), males and females exposed to olfactory, auditory, and visual stimuli from a vole of the opposite sex, but without physical contact; and (3) social cohabitation with mating (SCM), male and female voles copulating to induce pair bonding formation. Subsequently, the NPCs were isolated from the SVZ, maintained, and supplemented with growth factors to form neurospheres in vitro. RESULTS: Notably, we detected in SE and SCM voles, a higher proliferation of neurosphere-derived Nestin + cells, as well as an increase in mature neurons (MAP2 +) and a decrease in glial (GFAP +) differentiated cells with some sex differences. These data suggest that when voles are exposed to sociosexual experiences that induce pair bonding, undifferentiated cells of the SVZ acquire a commitment to a neuronal lineage, and the determined potential of the neurosphere is conserved despite adaptations under in vitro conditions. Finally, we repeated the culture to obtain neurospheres under treatments with different hormones and factors (brain-derived neurotrophic factor, estradiol, prolactin, oxytocin, and progesterone); the ability of SVZ-isolated cells to generate neurospheres and differentiate in vitro into neurons or glial lineages in response to hormones or factors is also dependent on sex and sociosexual context. CONCLUSION: Social interactions that promote pair bonding in voles change the properties of cells isolated from the SVZ. Thus, SE or SCM induces a bias in the differentiation potential in both sexes, while SE is sufficient to promote proliferation in SVZ-isolated cells from male brains. In females, proliferation increases when mating is performed. The next question is whether the rise in proliferation and neurogenesis of cells from the SVZ are plastic processes essential for establishing, enhancing, maintaining, or accelerating pair bond formation. Highlights 1. Sociosexual experiences that promote pair bonding (social exposure and social cohabitation with mating) induce changes in the properties of neural stem/progenitor cells isolated from the SVZ in adult prairie voles. 2. Social interactions lead to increased proliferation and induce a bias in the differentiation potential of SVZ-isolated cells in both male and female voles. 3. The differentiation potential of SVZ-isolated cells is conserved under in vitro conditions, suggesting a commitment to a neuronal lineage under a sociosexual context. 4. Hormonal and growth factors treatments (brain-derived neurotrophic factor, estradiol, prolactin, oxytocin, and progesterone) affect the generation and differentiation of neurospheres, with dependencies on sex and sociosexual context. 5. Proliferation and neurogenesis in the SVZ may play a crucial role in establishing, enhancing, maintaining, or accelerating pair bond formation.

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In this study, researchers evaluated whether social interactions and copulation induce changes in the proliferation and differentiation of neural progenitor cells in adult male and female voles using an in vitro neurosphere formation assay. The following groups were assigned: control animals without any exposure to another vole outside their litter, another group with social exposure consisting of sensory exposure to a vole of the opposite sex and a third group with social cohabitation and copulation. Forty eight hours after social interactions, cells were isolated from the neurogenic niche subventricular zone (SVZ) and cultured to assess their self-renewal and proliferation abilities to form neurospheres. The results showed in the social interaction groups, a greater number and growth of neurospheres in both males and females. Differentiation capacity was assessed by immunodetection of MAP2 and GFAP to identify neurons or glia, respectively, arise from neurospheres, with an increase in neuronal fate in groups with social interaction. In the second part of the study, the researchers analyzed the effect of different hormone and growth factor treatments and found that the response in both proliferation and differentiation potential may vary depending on the sociosexual context or sex. This study suggests that social interactions leading to pair bond formation alter the properties of SVZ cells, whereby proliferation and neurogenesis may have an impact on the establishment and maintenance of pair bonding.

Asunto(s)

Células-Madre Neurales , Caracteres Sexuales , Animales , Femenino , Masculino , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Oxitocina/metabolismo , Pradera , Prolactina/metabolismo , Progesterona , Neuronas/metabolismo , Encéfalo/metabolismo , Células-Madre Neurales/metabolismo , Arvicolinae/metabolismo , Proliferación Celular , Estradiol/metabolismo , Proteínas de Unión al ADN/metabolismo

RESUMEN

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.

Asunto(s)

Neoplasias de la Mama , Transducción de Señal , Humanos , Femenino , Transducción de Señal/fisiología , Quinasas Janus/metabolismo , Prolactina/metabolismo , Interleucina-6/metabolismo , Factores de Transcripción STAT/metabolismo

RESUMEN

Introduction: The prevalence of type 2 diabetes mellitus (T2DM) is increasing worldwide. Strategies to decrease this risk should be strongly encouraged. Lactation has been associated, for the mother, with reduction in future T2DM risk in several studies. The mechanisms behind this phenomenon, however, are poorly understood. The aims of this study were, first, to compare blood glucose levels and markers of insulin resistance (MIR) in early postpartum women with overweight/obesity according to their breastfeeding status and, second, to evaluate whether prolactin (PRL) levels could mediate improvements in these parameters. Methods: The prospective study followed 95 women older than 18 years from early pregnancy for up to 60 to 180 days postpartum. All participants had a BMI > 25 kg/m2 and a singleton pregnancy. At each visit, questionnaires and clinical and biochemical evaluations were performed. Participants were divided into two groups according to the breastfeeding status as "yes" for exclusive or predominant breastfeeding, and "no" for not breastfeeding. Results: Breastfeeding women (n = 44) had significantly higher PRL levels [47.8 (29.6-88.2) vs. 20.0 (12.0-33.8), p< 0.001]. They also had significantly lower fasting blood glucose levels [89.0 (8.0) vs. 93.9 (12.6) mg/dl, p = 0.04], triglycerides (TG) [92.2 (37.9) vs. 122.4 (64.4) mg/dl, p = 0.01], TG/HDL ratio [1.8 (0.8) vs. 2.4 (1.6) mg/dl, p = 0.02], TyG index [8.24 (0.4) vs. 8.52 (0.53), p = 0.005], fasting serum insulin [8.9 (6.3-11.6) vs. 11.4 (7.7-17.0), p = 0.048], and HOMA-IR [2.0 (1.3-2.7) vs. 2.6 (1.6-3.9), p = 0.025] in the postpartum period compared to the non-breastfeeding group. Groups were homogeneous in relation to prevalence of GDM, pre-gestational BMI, as well as daily caloric intake, physical activity, and weight loss at postpartum. Linear regression analysis with adjustments for confounders showed a statistically significant association of breastfeeding with fasting blood glucose [-6.37 (-10.91 to -1.83), p = 0.006], HOMA-IR [-0.27 (-0.51 to -0.04), p = 0.024], TyG index [-0.04 (-0.06 to -0.02), p = 0.001], and TG/HDL ratio [-0.25 (-0.48 to -0.01), p = 0.038]. Mediation analysis showed that PRL did not mediate these effects. Sensitivity analyses considering different cutoffs for PRL levels also did not show modification effect in the mediation analyses. Conclusion: Breastfeeding was associated with improvement in glucose metabolism and MIR 60 to 180 days after birth in overweight and obese women, even when adjusted for confounders. PRL levels were not found to mediate the association between breastfeeding and improvement in MIR.

Asunto(s)

Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Embarazo , Humanos , Femenino , Prolactina , Glucemia , Diabetes Mellitus Tipo 2/epidemiología , Sobrepeso , Estudios Prospectivos

RESUMEN

Maternal milk supports offspring development by providing microbiota, macronutrients, micronutrients, immune factors, and hormones. The hormone prolactin (PRL) is an important milk component with protective effects against metabolic diseases. Because maternal milk regulates microbiota composition and adequate microbiota protect against the development of metabolic diseases, we aimed to investigate whether PRL/PRL receptor signaling regulates gut microbiota composition in newborn mice at weaning. 16SrRNA sequencing of feces and bioinformatics analysis was performed to evaluate gut microbiota in PRL receptor-null mice (Prlr-KO) at weaning (postnatal day 21). The normalized colon and cecal weights were higher and lower, respectively, in the Prlr-KO mice relative to the wild-type mice (Prlr-WT). Relative abundances (Simpson Evenness Index), phylogenetic diversity, and bacterial concentrations were lower in the Prlr-KO mice. Eleven bacteria species out of 470 differed between the Prlr-KO and Prlr-WT mice, with two genera (Anaerotruncus and Lachnospiraceae) related to metabolic disease development being the most common in the Prlr-KO mice. A higher metabolism of terpenoids and polyketides was predicted in the Prlr-KO mice compared to the Prlr-WT mice, and these metabolites had antimicrobial properties and were present in microbe-associated pathogenicity. We concluded that the absence of the PRL receptor altered gut microbiota, resulting in lower abundance and richness, which could contribute to metabolic disease development.

Asunto(s)

Microbioma Gastrointestinal , Receptores de Prolactina , Ratones , Animales , Receptores de Prolactina/genética , Receptores de Prolactina/metabolismo , Destete , Filogenia , Prolactina , Ratones Noqueados

RESUMEN

In birds, parental care and attachment period differ widely depending on the species (altricial or precocial), developmental strategies, and life history traits. In most bird species, parental care can be provided by both female and male individuals and includes specific stages such as nesting, laying, and hatching. During said periods, a series of neuroendocrine responses are triggered to motivate parental care and attachment. These behaviors are vital for offspring survival, development, social bonding, intergenerational learning, reproductive success, and ultimately, the overall fitness and evolution of bird populations in a variety of environments. Thus, this review aims to describe and analyze the behavioral and endocrine systems of parental care and newborn attachment in birds during each stage of the post-hatching period.

RESUMEN

The RF-amide peptides comprise a family of neuropeptides that includes the kisspeptin (Kp), the natural ligand of kisspeptin receptor (Kiss1r), and the RFamide-related peptide 3 (RFRP-3) that binds preferentially to the neuropeptide FF receptor 1 (Npffr1). Kp stimulates prolactin (PRL) secretion through the inhibition of tuberoinfundibular dopaminergic (TIDA) neurons. Because Kp also has affinity to Npffr1, we investigated the role of Npffr1 in the control of PRL secretion by Kp and RFRP-3. Intracerebroventricular (ICV) injection of Kp increased PRL and LH secretion in ovariectomized, estradiol-treated rats. The unselective Npffr1 antagonist RF9 prevented these responses, whereas the selective antagonist GJ14 altered PRL but not LH levels. The ICV injection of RFRP-3 in ovariectomized, estradiol-treated rats increased PRL secretion, which was associated with a rise in the dopaminergic activity in the median eminence, but had no effect on LH levels. The RFRP-3-induced increase in PRL secretion was prevented by GJ14. Moreover, the estradiol-induced PRL surge in female rats was blunted by GJ14, along with an amplification of the LH surge. Nevertheless, whole-cell patch clamp recordings showed no effect of RFRP-3 on the electrical activity of TIDA neurons in dopamine transporter-Cre recombinase transgenic female mice. We provide evidence that RFRP-3 binds to Npffr1 to stimulate PRL release, which plays a role in the estradiol-induced PRL surge. This effect of RFRP-3 is apparently not mediated by a reduction in the inhibitory tone of TIDA neurons but possibly involves the activation of a hypothalamic PRL-releasing factor.

Asunto(s)

Neuropéptidos , Prolactina , Ratones , Ratas , Femenino , Animales , Humanos , Prolactina/farmacología , Prolactina/metabolismo , Kisspeptinas , Estradiol/farmacología , Ovariectomía

RESUMEN

Serum prolactin increases from birth to adulthood in rats, being higher in females from birth. The maturation of hypothalamic/gonadal prolactin-releasing and -inhibiting factors does not explain some sex differences observed. During the first weeks of life, prolactin secretion increases, even when lactotrophs are isolated in vitro, in the absence of those controls, suggesting the participation of intra-pituitary factors in this control. The present work aimed to study the involvement of pituitary activins in the regulation of prolactin secretion during post-natal development. Sex differences were also highlighted. Female and male Sprague-Dawley rats at 11, 23 and 45postnatal days were used. Pituitary expression of activin subunits and activin receptors was maximum in p11 female pituitaries, being even higher than that observed in males. Those expressions decrease with age in females, and then the gender differences disappear at p23. Inhbb expression strongly increases at p45 in males, being the predominant subunit in this sex in adulthood. Activin inhibition of prolactin is mediated by the inhibition of Pit-1 expression. This action involves not only the canonical pSMAD pathway but also the phosphorylation of p38MAPK. At p11, almost all lactotrophs express p-p38MAPK in females, and its expression decreases with age with a concomitant increase in Pit-1. Our findings suggest that the inhibitory regulation of pituitary activins on prolactin secretion is sex specific; this regulation is more relevant in females during the first week of life and decreases with age; this intra-pituitary regulation is involved in the sex differences observed in serum prolactin levels during postnatal development.

Asunto(s)

Lactotrofos , Prolactina , Femenino , Ratas , Masculino , Animales , Prolactina/metabolismo , Activinas/metabolismo , Ratas Sprague-Dawley , Hipófisis/metabolismo , Lactotrofos/metabolismo , Factores de Transcripción/metabolismo

RESUMEN

The close interaction between fetal and maternal cells during pregnancy requires multiple immune-endocrine mechanisms to provide the fetus with a tolerogenic environment and protection against any infectious challenge. The fetal membranes and placenta create a hyperprolactinemic milieu in which prolactin (PRL) synthesized by the maternal decidua is transported through the amnion-chorion and accumulated into the amniotic cavity, where the fetus is bedded in high concentrations during pregnancy. PRL is a pleiotropic immune-neuroendocrine hormone with multiple immunomodulatory functions mainly related to reproduction. However, the biological role of PRL at the maternal-fetal interface has yet to be fully elucidated. In this review, we have summarized the current information on the multiple effects of PRL, focusing on its immunological effects and biological significance for the immune privilege of the maternal-fetal interface.

Asunto(s)

Decidua , Prolactina , Embarazo , Femenino , Humanos , Placenta , Membranas Extraembrionarias , Líquido Amniótico