RESUMEN

The microalgae Neochloris aquatica were previously evaluated as a potential biological control agent and source of bioactive compounds against immature stages of Culex quinquefasciatus. Larvae reared on microalgae suspension showed mortality or drastic effects with morphological alterations and damage in the midgut. N. aquatica have nutritional and toxic effects, resulting in delayed life cycle and incomplete adult development. Given the possibility of its use as a biological control agent, in this work we evaluate the effect of microalgae on other organisms of the environment, such as plants. Arabidopsis thaliana, a terrestrial plant, and Lemna sp., a floating aquatic plant, were selected as examples. Interaction assays and compound evaluations showed that the microalgae release auxins causing root inhibition, smaller epidermal cells and hairy root development. In Lemna sp., a slight decrease in growth rate was observed, with no deleterious effects on the fronds. On the other hand, we detected a detrimental effect on plants when interactions were performed in a closed environment, in a medium containing soluble carbonate, in which microalgae culture rapidly modifies the pH. The experiments showed that alkalinization of the medium inhibits plant growth, causing bleaching of leaves or fronds. This negative effect in plants was not observed when plants and microalgae were cultured in carbonate-free media. In conclusion, the results showed that N. aquatica can modify plant growth without being harmful, but the rapid alkalinization produced by carbon metabolism of microalgae under CO2-limiting conditions, could regulate the number of plants.

Asunto(s)

Arabidopsis , Microalgas , Agentes de Control Biológico/farmacología , Plantas , Hormonas/farmacología

RESUMEN

Resistance to therapy remains a major obstacle in cancer management. Although treatment with hormone and CDK4/6 inhibitors is successful in luminal breast cancer, resistance to these treatments is frequent, highlighting the need for novel therapeutic strategies to delay disease progression and improve patient survival. Here, we assessed the mechanisms of acquired resistance using T47D and MCF-7 tamoxifen- and palbociclib-resistant cell-line variants in culture and as xenografts, and patient-derived cells (PDCs) obtained from sensitive or resistant patient-derived xenografts (PDXs). In these models, we analyzed the effect of specific kinase inhibitors on survival, signaling and cellular aggressiveness. Our results revealed that mTOR inhibition is more effective than PI3K inhibition in overcoming resistance, irrespective of PIK3CA mutation status, by decreasing cell proliferation and tumor growth, as well as reducing cell migration and stemness. Moreover, a combination of mTOR and CDK4/6 inhibitors may prevent pathway reactivation downstream of PI3K, interfering with the survival of resistant cells and consequent tumor escape. In conclusion, we highlight the benefits of incorporating mTOR inhibitors into the current therapy in ER + breast cancer. This alternative therapeutic strategy not only enhances the antitumor response but may also delay the emergence of resistance and tumor recurrence.

Asunto(s)

Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/patología , Resistencia a Antineoplásicos , Línea Celular Tumoral , Recurrencia Local de Neoplasia , Serina-Treonina Quinasas TOR/metabolismo , Hormonas/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Quinasa 4 Dependiente de la Ciclina , Quinasa 6 Dependiente de la Ciclina

RESUMEN

p-Coumaric acid is derived from cinnamic acid and is one of the major compounds in the Brazilian green propolis extract. Studies have shown that both p-coumaric acid and cinnamic acid have promising antiproliferative effects. In this context, aiming to increase the complexity of these active natural products and their activities, we performed coupling reactions with propargylamine and benzylamine, as well as with threonine, phenylalanine and lysine amino acids, aiming to enhance their antiproliferative effects towards the hormone-dependent breast cancer MCF-7 cells. Overall, the p-coumaric acid coupling with L-threonine amino acid (compound 15) had the best selectivity index (SI = 5.1), with half-maximal inhibitory concentration of 39.6 ± 1 µM, showing a high selectivity against hormone-dependent breast cancer cell lines MCF-7 and low cytotoxicity against the normal breast cell lines MCF-10A. Thus, this new natural product derivative may represent a prototype for the future development of antiproliferative agents, especially against hormone-dependent breast cancer.

Asunto(s)

Antineoplásicos , Neoplasias de la Mama , Humanos , Femenino , Ácidos Cumáricos/farmacología , Células MCF-7 , Antineoplásicos/química , Neoplasias de la Mama/tratamiento farmacológico , Hormonas/farmacología , Hormonas/uso terapéutico , Proliferación Celular , Línea Celular Tumoral

RESUMEN

Inflammation and oxidative stress are critical events involved in neurodegeneration. In animal models, it has been shown that chronic consumption of a hypercaloric diet, which leads to inflammatory processes, affects the hippocampus, a brain region fundamental for learning and memory processes. In addition, advanced age and menopause are risk factors for neurodegeneration. Hormone replacement therapy (HRT) ameliorates menopause symptoms. Tibolone (TB), a synthetic hormone, exerts estrogenic, progestogenic and androgenic effects on different tissues. We aimed to determine the effect of short-term TB administration on oxidative stress and inflammation markers in the hippocampus of ovariectomized rats fed a high-fat-and-fructose diet (HFFD). Adult female rats were ovariectomized (OVX) and fed standard diet or HFFD-consisting of 10% lard supplemented chow and 20% high-fructose syrup in the drinking water-and administered vehicle or TB (1 mg/kg for seven days). Finally, we administered hormone receptor antagonists (MPP, RU486 or FLU) to each of the OVX + HFFD + TB groups. Bodyweight, triglycerides and cholesterol, oxidative stress and inflammation markers, and the activity and expression of antioxidant enzymes were quantified in the hippocampus of each experimental group. We observed that short-term TB administration significantly reduced body weight, AGEs, MDA levels, increased SOD and GPx activity, improved GSH/GSSG ratio, and reduced IL-6 and TNF-α. Our findings suggest that short-term administration of TB decreases oxidative stress and reduces inflammation caused by HFFD and early estrogenic decline. These effects occurred via estrogen receptor alpha.

Asunto(s)

Fructosa , Estrés Oxidativo , Ratas , Femenino , Animales , Fructosa/efectos adversos , Inflamación/metabolismo , Dieta Alta en Grasa/efectos adversos , Peso Corporal , Hipocampo/metabolismo , Hormonas/metabolismo , Hormonas/farmacología

RESUMEN

OBJECTIVE: To evaluate the therapeutic potential of vitamin D receptor (VDR) signaling in adrenocortical carcinoma (ACC) cells. METHODS: We evaluated VDR's methylation pattern in H295R ACC cells, and investigated the effects of calcitriol and seocalcitol treatments on adrenocortical tumorigenesis. RESULTS: VDR was hypermethylated and underexpressed in basal H295R cells. Treatments with calcitriol and seocalcitol restored VDR signaling, resulted in antiproliferative effects, and impaired Wnt/B-catenin signaling. RNAseq of treated cells demonstrated VDR activation on steroid hormones biosynthesis and Rap1 signaling, among others. In vivo, seocalcitol constrained the growth of H295R xenografts and reduced autonomous tumor steroid secretion without hypercalcemia-associated side effects. CONCLUSIONS: H295R cells present VDR hypermethylation, which can be responsible for its underexpression and signaling inactivation under basal conditions. VDR signaling promoted antiproliferative effects in vitro and in vivo, suggesting that it may be a potential therapeutic target for ACC and a valuable tool for patient's clinical management.

Asunto(s)

Neoplasias de la Corteza Suprarrenal , Carcinoma Corticosuprarrenal , Humanos , Neoplasias de la Corteza Suprarrenal/tratamiento farmacológico , Neoplasias de la Corteza Suprarrenal/genética , Carcinoma Corticosuprarrenal/tratamiento farmacológico , Carcinoma Corticosuprarrenal/genética , Calcitriol/farmacología , Carcinogénesis/genética , Cateninas/farmacología , Línea Celular Tumoral , Transformación Celular Neoplásica , Hormonas/farmacología , Receptores de Calcitriol/genética , Vitamina D/farmacología , Vía de Señalización Wnt

RESUMEN

Here we investigated the effects of physical training on cardiovascular autonomic control and cardiac morphofunctional parameters in spontaneously hypertensive rats (SHRs) subjected to ovarian hormone deprivation. Forty-eight 10-week-old SHRs were divided into two groups: ovariectomized (OVX, n=24) and sham (SHAM, n=24). Half of each group (n=12) was trained by swimming for 12 weeks (OVX-T and SHAM-T). Cardiac morphology and functionality were assessed using echocardiography, and autonomic parameters were assessed using double pharmacological autonomic block, baroreflex sensitivity (BRS), and analyses of heart rate variability (HRV) and blood pressure variability (BPV). Ovariectomy did not influence the cardiac autonomic tonus balance unlike physical training, which favored greater participation of the vagal autonomic tonus. Ovariectomy and aerobic physical training did not modify HRV and BRS, unlike BPV, for which both methods reduced low-frequency oscillations, suggesting a reduction in sympathetic vascular modulation. Untrained ovariectomized animals showed a reduced relative wall thickness (RWT) and increased diastolic and systolic volumes and left ventricular diameters, resulting in increased stroke volume. Trained ovariectomized animals presented reduced posterior wall thickness and RWT as well as increased final diastolic diameter, left ventricular mass, and stroke volume. Ovarian hormone deprivation in SHRs promoted morphofunctional adaptations but did not alter the evaluation of cardiac autonomic parameters. In turn, aerobic physical training contributed to a more favorable cardiac autonomic balance to the vagal autonomic component and promoted morphological adaptations but had little effect on cardiac functionality.

Asunto(s)

Hipertensión , Condicionamiento Físico Animal , Animales , Sistema Nervioso Autónomo/fisiología , Barorreflejo/fisiología , Presión Sanguínea/fisiología , Femenino , Corazón , Frecuencia Cardíaca/fisiología , Hormonas/farmacología , Hipertensión/terapia , Condicionamiento Físico Animal/fisiología , Ratas , Ratas Endogámicas SHR , Ratas Wistar

RESUMEN

This study investigated whether norepinephrine (NE) and epinephrine (E) interfere in the response of head and neck squamous cell carcinoma (SCC) cell lines to cisplatin and explored the mechanisms of chemoresistance. Head and neck SCC-derived cell lines SCC-9, Cal27, SCC-25, and FaDu were stimulated with NE or E and treated with the inhibitory concentration of cisplatin for 24 h. As for adrenergic receptors (ADRB) inhibition, cells were treated with propranolol. The results showed that, when combined with NE, cisplatin effectiveness against SCC-9 and Cal27 but not SCC-25 and FaDu cells were notably reduced. E did not affect the response of the cells to cisplatin. Further experiments were performed with the responsive SCC-9 and SCC-25 cell lines and the hormone NE. The time course assay showed that stimulation of oral SCC cells with NE decreased the cleavage of caspase-3 and expression of multidrug resistance protein 1 (MDR-1) but only transiently affected ATP-binding cassette (ABC) subfamily G, isoform 2 protein (ABCG2) expression. The expression of cleaved caspase-3 and Bcl-2 were, respectively, decreased and increased by the combination of NE and cisplatin in SCC-9 and Cal27 cells. NE-induced resistance was reverted by previous treatment with propranolol. Expressions of ABCG2, and p-Akt but not of MDR-1, were enhanced by NE plus cisplatin when compared to cisplatin only in both cell lines. Migratory activity of oral SCC cells challenged with cisplatin was not affected by NE. These findings reveal for the first time that stress hormone NE induces resistance of oral cancer cells to cisplatin in vitro through the ADRB/Akt/ABCG2 pathway, pumping the drug out of the cell and inhibiting apoptosis.

Asunto(s)

Antineoplásicos , Neoplasias de la Boca , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/metabolismo , Transportadoras de Casetes de Unión a ATP/metabolismo , Transportadoras de Casetes de Unión a ATP/farmacología , Antineoplásicos/farmacología , Línea Celular Tumoral , Cisplatino/farmacología , Resistencia a Múltiples Medicamentos , Resistencia a Antineoplásicos , Hormonas/farmacología , Humanos , Neoplasias de la Boca/tratamiento farmacológico , Proteínas de Neoplasias/metabolismo , Norepinefrina/farmacología

RESUMEN

The effects of an adequate supply of vitamin A and iron, in comparison with diets low or absent in vitamin A and low in iron, on the mRNA expression of some biomarkers of iron homeostasis as hepcidin (Hamp), transferrin receptor-1 (Tfrc), iron regulatory protein-2 (Ireb2) and ferritin (Fth1) in rats were investigated. 35 male Wistar rats were randomly divided into 5 dietary groups: control, sufficient in iron and insufficient in vitamin A (FesvAi), sufficient in iron and depleted in vitamin A (FesvAd), insufficient in iron and sufficient in vitamin A (FeivAs) and insufficient in both iron and vitamin A (FeivAi). After 6 weeks rats showed no significant effects of variations in vitamin A on the expression of Hamp relative to the control group (FesvAi: 1.37-fold; FesvAd: 1.22-fold); however, iron deficiency showed significant reduction on it relative to the control group (FeivAs: 71.4-fold, P = 0.0004; FeivAi: 16.1-fold, P = 0.0008). Vitamin A deficiency (FesvAd) affects expression of Fth1 independent of low dietary iron in spleen (0.29-fold, P = 0.002) and duodenum (5.15-fold, P = 0.02). Variations of dietary iron and vitamin A showed significant effects relative to the control group for expression of Tfrc in spleen (FesvAd: 0.18-fold, P = 0.01; FeivAs: 0.24-fold, P < 0.0001; FeivAi: 0.42-fold, P = 0.014), Ireb2 in spleen (FeivAs: 3.7-fold, P < 0.0001; FeivAi: 2.9-fold, P < 0.0001) and Ireb2 in duodenum (FeivAs: 2.68-fold, P = 0.012; FeivAi: 2.60-fold, P = 0.014). These results show that vitamin A and iron must be supplied together to regulate some of the main biomarkers of iron metabolism as a strategy to reduce prevalence of iron deficiency anemia.

Asunto(s)

Anemia Ferropénica , Hepcidinas , Animales , Biomarcadores , Hepcidinas/genética , Hepcidinas/metabolismo , Hepcidinas/farmacología , Homeostasis , Hormonas/farmacología , Hierro/metabolismo , Hierro de la Dieta , Masculino , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas Wistar , Vitamina A/farmacología

RESUMEN

Chronic stress increases the systemic levels of stress hormones norepinephrine and cortisol. As well as tobacco-specific carcinogen NNK (4-(methylnitrosamine)-1-(3-pyridyl)-1-butanone), they can induce expressive DNA damage contributing to the cancer development. However, it is unknown whether stress hormones have genotoxic effects in oral keratinocytes. This study investigated the effects of stress hormones on DNA damage in a human oral keratinocyte cell line (NOK-SI). NOK-SI cells stimulated with norepinephrine or cortisol showed higher DNA damage compared to untreated cells. Norepinephrine-induced DNA damage was reversed by pre-treatment with beta-adrenergic blocker propranolol. Cells treated with NNK combined to norepinephrine displayed reduced levels of caspases 3 and 7. Cortisol also reduced the activity of pro-apoptotic enzymes. NNK or norepinephrine promoted single-strand breaks and alkali-label side breaks in the DNA of NOK-SI cells. Pre-treatment of cells with propranolol abolished these effects. Carcinogen NNK in the presence or absence of cortisol also induced DNA damage of these cells. The genotoxic effects of cortisol alone and hormone combined with NNK were blocked partially and totally, respectively, by the glucocorticoid receptor antagonist RU486. DNA damage promoted by NNK or cortisol and carcinogen combined to the hormone led to intracellular γH2AX accumulation. The effects caused by NNK and cortisol were reversed by propranolol and glucocorticoid receptor antagonist RU486, respectively. Propranolol inhibited the oxidation of basis induced by NNK in the presence of DNA-formamidopyrimidine glycosylase. DNA breaks induced by norepinephrine in the presence or absence of NNK resulted in higher 8OHdG cellular levels. This effect was also induced through beta-adrenergic receptors. Together, these findings indicate that stress hormones induce DNA damage of oral keratinocytes and could contribute to oral carcinogenesis.

Asunto(s)

Daño del ADN , Hormonas/metabolismo , Queratinocitos/metabolismo , Mucosa Bucal/metabolismo , Estrés Fisiológico , 8-Hidroxi-2'-Desoxicoguanosina/metabolismo , Apoptosis , Roturas del ADN/efectos de los fármacos , Daño del ADN/efectos de los fármacos , Células Epiteliales , Histonas/metabolismo , Hormonas/farmacología , Humanos , Hidrocortisona/farmacología , Queratinocitos/efectos de los fármacos , Nitrosaminas/química , Nitrosaminas/farmacología , Norepinefrina/farmacología , Oxidación-Reducción , Nicotiana/química

RESUMEN

OBJECTIVES: To conduct a cost-utility analysis comparing drug strategies involving octreotide, lanreotide, pasireotide, and pegvisomant for the treatment of patients with acromegaly who have failed surgery, from a Brazilian public payer perspective. METHODS: A probabilistic cohort Markov model was developed. One-year cycles were employed. The patients started at 45 years of age and were followed lifelong. Costs, efficacy, and quality of life parameters were retrieved from the literature. A discount rate (5%) was applied to both costs and efficacy. The results were reported as costs per quality-adjusted life year (QALY), and incremental cost-effectiveness ratios (ICERs) were calculated when applicable. Scenario analyses considered alternative dosages, discount rate, tax exemption, and continued use of treatment despite lack of response. Value of information (VOI) analysis was conducted to explore uncertainty and to estimate the costs to be spent in future research. RESULTS: Only lanreotide showed an ICER reasonable for having its use considered in clinical practice (R$ 112,138/US$ 28,389 per QALY compared to no treatment). Scenario analyses corroborated the base-case result. VOI analysis showed that much uncertainty surrounds the parameters, and future clinical research should cost less than R$ 43,230,000/US$ 10,944,304 per year. VOI also showed that almost all uncertainty that precludes an optimal strategy choice involves quality of life. CONCLUSIONS: With current information, the only strategy that can be considered cost-effective in Brazil is lanreotide treatment. No second-line treatment is recommended. Significant uncertainty of parameters impairs optimal decision-making, and this conclusion can be generalized to other countries. Future research should focus on acquiring utility data.

Asunto(s)

Acromegalia/tratamiento farmacológico , Acromegalia/economía , Antineoplásicos , Análisis Costo-Beneficio , Hormonas , Hormona de Crecimiento Humana/análogos & derivados , Octreótido , Evaluación de Resultado en la Atención de Salud , Péptidos Cíclicos , Somatostatina/análogos & derivados , Antineoplásicos/economía , Antineoplásicos/farmacología , Brasil , Hormonas/economía , Hormonas/farmacología , Hormona de Crecimiento Humana/economía , Hormona de Crecimiento Humana/farmacología , Humanos , Programas Nacionales de Salud , Octreótido/economía , Octreótido/farmacología , Evaluación de Resultado en la Atención de Salud/economía , Evaluación de Resultado en la Atención de Salud/estadística & datos numéricos , Péptidos Cíclicos/economía , Péptidos Cíclicos/farmacología , Somatostatina/economía , Somatostatina/farmacología

RESUMEN

A research career is not only built on ideas and publishable results; it is more often the product of determination, hard work, collegiality and collaboration. It is through our collaborators, family and friends that we really become better persons, and scientists. It is also a matter of being at the right place at the right time. My work in bovine reproduction has progressed from an interest in superovulation and embryo transfer before I became a veterinarian, to the development and application of this technology and fixed-time artificial insemination in beef and dairy herds. Everything that I have done has been possible because of the people that I have worked with over the years. This manuscript combines some of the very exciting things that I have learned about bovine reproduction over the last 30 years and personal stories behind the projects and ideas that we have pursued during that time.

Asunto(s)

Bovinos/fisiología , Hormonas/farmacología , Ovario/efectos de los fármacos , Ovario/fisiología , Ovulación/fisiología , Animales , Distinciones y Premios , Femenino , Historia del Siglo XX , Historia del Siglo XXI , Hormonas/administración & dosificación , Ovulación/efectos de los fármacos , Técnicas Reproductivas Asistidas/veterinaria , América del Sur

RESUMEN

Artibeus lituratus is a frugivorous bat that directly assists in the restoration of degraded habitats through the effective dispersion of seeds and fruits. Given its great importance, this work aimed to evaluate the uterine hormonal control of A. lituratus during its different reproductive phases. The uteri of 30 sexually mature adult females, five specimens for each of the six sample groups (NON, nonreproductive; P1, initial pregnancy; P2, intermediate pregnancy; P3, advanced pregnancy; LAC, lactating; P + LAC, pregnant-lactating), were submitted to analyses of serum estradiol and progesterone concentrations, in addition to immunohistochemical analyses. Both estradiol and progesterone, gradually increased during pregnancy, with a marked significant increase in P3 females. Both returned to low levels in LAC-females; however, estradiol levels decreased further in P + LAC-females, while progesterone increased in the same group. In general, signs indicative of aromatase expression were observed in the endometrium of all analyzed groups and in the placenta of bats in the gestation groups. Similarly, ERα and PR were expressed in the myometrium, endometrium and placenta at varying levels of intensity. The results indicate that the uterine microenvironment of A. lituratus is directly regulated by serum concentrations of estradiol and progesterone, and fluctuations in these concentrations control morphological and physiological changes of this organ during different phases of the reproductive cycle. RESEARCH HIGHLIGHTS: Increases in serum concentrations of estradiol and progesterone coordinate the gestational period of A. lituratus. Estradiol activates ERα, stimulating cell proliferation in the uterus, in addition to activating the expression of PR, which trigger the quiescence of the myometrium and stimulation of the secretion and differentiation of the endometrium. Results showed several similarities to humans, indicating the use of A. lituratus as an animal model in reproductive studies.

Asunto(s)

Quirópteros/fisiología , Hormonas/farmacología , Reproducción/fisiología , Útero/fisiología , Animales , Aromatasa/metabolismo , Proliferación Celular/efectos de los fármacos , Receptor alfa de Estrógeno/metabolismo , Femenino , Antígeno Nuclear de Célula en Proliferación/metabolismo , Receptores de Progesterona/metabolismo , Útero/anatomía & histología , Útero/citología , Útero/efectos de los fármacos

RESUMEN

The liver is considered the laboratory of the human body because of its many metabolic processes. It accomplishes diverse activities as a mixed gland and is in continuous cross-talk with the endocrine system. Not only do hormones from the gastrointestinal tract that participate in digestion regulate the liver functions, but the sex hormones also exert a strong influence on this sexually dimorphic organ, via their receptors expressed in liver, in both health and disease. Besides, the liver modifies the actions of sex hormones through their metabolism and transport proteins. Given the anatomical position and physiological importance of liver, this organ is evidenced as an immune vigilante that mediates the systemic immune response, and, in turn, the immune system regulates the hepatic functions. Such feedback is performed by cytokines. Pro-inflammatory and anti-inflammatory cytokines are strongly involved in hepatic homeostasis and in pathological states; indeed, female sex hormones, oral contraceptives, and phytoestrogens have immunomodulatory effects in the liver and the whole organism. To analyze the complex and interesting beneficial or deleterious effects of these drugs by their immunomodulatory actions in the liver can provide the basis for either their pharmacological use in therapeutic treatments or to avoid their intake in some diseases.

Asunto(s)

Anticonceptivos Orales/metabolismo , Hormonas/metabolismo , Inmunomodulación , Hígado/inmunología , Hígado/metabolismo , Fitoestrógenos/metabolismo , Anticonceptivos Orales/farmacología , Femenino , Hormonas/farmacología , Humanos , Sistema Inmunológico/efectos de los fármacos , Sistema Inmunológico/inmunología , Sistema Inmunológico/metabolismo , Inmunomodulación/efectos de los fármacos , Hígado/efectos de los fármacos , Estructura Molecular , Fitoestrógenos/farmacología , Factores Sexuales

RESUMEN

Accurate diagnosis and treatment of pain is dependent on knowledge of the variables that might alter this response. Some of these variables are the locality of the noxious stimulus, the sex of the individual, and the presence of chronic diseases. Among these chronic diseases, hypertension is considered a serious and silent disease that has been associated with hypoalgesia. The main goal of this study was to evaluate the potential nociceptive differences in spontaneously hypertensive rats (SHR) regarding the locality of the stimulus, i.e., the temporomandibular joint or paw, the sex, and the role of ovarian hormones in a model of mechanical nociception (Von Frey test) or formalin-induced inflammatory nociception. Our results indicate that SHR had lower orofacial mechanical nociception beyond the lower mechanical nociception in the paw compared with WKY rats. In a model of formalin-induced inflammatory nociception, SHR also had decreased nociception compared with normotensive rats. We also sought to evaluate the influence of sex and ovarian hormones on orofacial mechanical nociception in SHR. We observed that female SHR had higher mechanical nociception than male SHR only in the paw, but it had higher formalin-induced orofacial nociception than male SHR. Moreover, the absence of ovarian hormones caused an increase in mean arterial pressure and a decrease in paw nociception in female SHR.

Asunto(s)

Hormonas/farmacología , Hipertensión/fisiopatología , Nocicepción/fisiología , Caracteres Sexuales , Animales , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiología , Femenino , Hormonas/metabolismo , Hipertensión/metabolismo , Masculino , Nocicepción/efectos de los fármacos , Ovario , Dolor/fisiopatología , Dimensión del Dolor , Ratas Endogámicas SHR/metabolismo , Ratas Endogámicas WKY

RESUMEN

Glucocorticoids (GCs) such as cortisol and corticosterone are important steroid hormones with different functions in intermediate metabolism, development, cell differentiation, immune response and reproduction. In response to physiological and immunological stress, adrenocorticotropic hormone (ACTH) acts on the adrenal gland by stimulating the synthesis and secretion of GCs. However, there is increasing evidence that GCs may also be synthesized by extra-adrenal tissues. Here, we examined the gene and protein expression of the enzyme 11ß-hydroxylase P450c11 (CYP11B1), involved in the conversion of 11-deoxycortisol to cortisol, in the different components of the bovine ovary and determined the functionality of CYP11B1 in vitro CYP11B1 mRNA was expressed in granulosa and theca cells in small, medium and large antral ovarian follicles, and CYP11B1 protein was expressed in medium and large antral follicles. After stimulation by ACTH, we observed an increased secretion of cortisol by the wall of large antral follicles. We also observed a concentration-dependent decrease in the concentration of cortisol in response to metyrapone, an inhibitor of CYP11B1. This decrease was significant at 10-5 µM metyrapone. In conclusion, this study demonstrated for the first time the presence of CYP11B1 in the bovine ovary. This confirms that there could be a local synthesis of GCs in the bovine ovary and therefore a potential endocrine responder to stress through these hormones.

Asunto(s)

Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Folículo Ovárico/enzimología , Esteroide 11-beta-Hidroxilasa/metabolismo , Hormona Adrenocorticotrópica/farmacología , Animales , Bovinos , Células Cultivadas , Femenino , Hormonas/farmacología , Hidrocortisona/metabolismo , Folículo Ovárico/citología , Esteroide 11-beta-Hidroxilasa/genética

RESUMEN

The aims of this study were to investigate the effects of medium replacement system (experiment I) and of FSH presentations (homeopathic - FSH 6cH and allopathic FSH - rFSH; experiment II) on the in vitro development, hormone production and gene expression of isolated ovine preantral follicles cultured for 6 days. In experiment I, secondary follicles were cultured in the α-MEM+ supplemented with FSH 6cH (0.05 fg/ml) or recombinant bovine FSH (100 ng/ml) without/with daily medium addition. The homeopathic FSH treatments with/without medium addition improved (p < .05) follicular development compared to rFSH100 treatment without addition. FSH 6cH with addition showed the highest (p < .05) estradiol production. To verify whether the effects of homeopathic FSH were not due to its vehicle, experiment II was performed. The α-MEM+ was supplemented or not with alcohol (0.2% grain ethanol, v/v), FSH 6cH or rFSH100 with daily medium addition. Surprisingly, we found that all treatments improved follicular development compared to the α-MEM+ (p < .05). Moreover, homeopathic FSH was similar to the other treatments including its vehicle. In conclusion, its vehicle (ethanol) causes the effect of homeopathic FSH on in vitro development of isolated ovine preantral follicles.

Asunto(s)

Proliferación Celular/efectos de los fármacos , Etanol/farmacología , Hormona Folículo Estimulante/farmacología , Hormonas/biosíntesis , Técnicas de Cultivo de Órganos/métodos , Folículo Ovárico/crecimiento & desarrollo , Animales , Apoptosis/genética , Caspasa 3/análisis , Conexina 43/análisis , Conexinas/análisis , Fragmentación del ADN , Estradiol/biosíntesis , Etanol/química , Femenino , Homeopatía , Hormonas/farmacología , Folículo Ovárico/efectos de los fármacos , Progesterona/biosíntesis , Proteínas Recombinantes/farmacología , Ovinos , Proteína alfa-4 de Unión Comunicante

RESUMEN

Follicle-stimulating hormone (FSH) stimulates the proliferation of immature Sertoli cells through the activation of PI3K/AKT/mTORC1 and MEK/ERK1/2 pathways. Mature Sertoli cells stop proliferating and respond to FSH by stimulating cAMP production. To gain insight into possible mechanisms involved in this switch as well as the impact of paracrine factors that stimulate cell proliferation, we analyzed the effects of FSH and relaxin on intracellular signaling pathways involved with proliferation and differentiation in Sertoli cells from 15-day-old rats, which are close to the transition between the two stages. FSH stimulated 3H-thymidine incorporation and cyclin D1 expression, changes associated with proliferation. In contrast, FSH inhibited AKT and ERK1/2 phosphorylation, activated cAMP production and induced changes in several cell cycle genes that were compatible with differentiation. Relaxin also stimulated 3H-thymidine incorporation but increased phosphorylation of ERK1/2 and AKT. When both hormones were added simultaneously, relaxin attenuated FSH-mediated inhibition of ERK1/2 and AKT phosphorylation and FSH-mediated activation of cAMP production. FSH but not relaxin increased CREB phosphorylation, and relaxin but not FSH shifted NF-κB expression from the cytoplasm to the nucleus. Relaxin did not inhibit the effects of FSH on inhibin α and Bcl2 expression. We propose that at this time of Sertoli cell development, FSH starts to direct cells to differentiation through activation of cAMP/CREB and inhibition of ERK1/2 and AKT pathways. Relaxin counteracts FSH signaling through the inhibition of cAMP and activation of ERK1/2, AKT and NF-κB, but does not block the differentiation process triggered by FSH.

Asunto(s)

Proliferación Celular/efectos de los fármacos , Hormona Folículo Estimulante/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Relaxina/farmacología , Células de Sertoli/citología , Animales , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Diferenciación Celular/efectos de los fármacos , Células Cultivadas , Hormonas/farmacología , Masculino , Fosforilación/efectos de los fármacos , Ratas , Ratas Wistar , Células de Sertoli/efectos de los fármacos , Células de Sertoli/metabolismo , Transducción de Señal/efectos de los fármacos

RESUMEN

Pancreatic beta cells, unique cells that secrete insulin in response to an increase in glucose levels, play a significant role in glucose homeostasis. Glucose-stimulated insulin secretion (GSIS) in pancreatic beta cells has been extensively explored. In this mechanism, glucose enters the cells and subsequently the metabolic cycle. During this process, the ATP/ADP ratio increases, leading to ATP-sensitive potassium (KATP) channel closure, which initiates depolarization that is also dependent on the activity of TRP nonselective ion channels. Depolarization leads to the opening of voltage-gated Na(+) channels (Nav) and subsequently voltage-dependent Ca(2+) channels (Cav). The increase in intracellular Ca(2+) triggers the exocytosis of insulin-containing vesicles. Thus, electrical activity of pancreatic beta cells plays a central role in GSIS. Moreover, many growth factors, incretins, neurotransmitters, and hormones can modulate GSIS, and the channels that participate in GSIS are highly regulated. In this review, we focus on the principal ionic channels (KATP, Nav, and Cav channels) involved in GSIS and how classic and new proteins, hormones, and drugs regulate it. Moreover, we also discuss advances on how metabolic disorders such as metabolic syndrome and diabetes mellitus change channel activity leading to changes in insulin secretion.

Asunto(s)

Hormonas/farmacología , Células Secretoras de Insulina/metabolismo , Insulina/metabolismo , Canales Iónicos/metabolismo , Preparaciones Farmacéuticas/metabolismo , Adenosina Trifosfato/farmacología , Animales , Glucosa/farmacología , Humanos , Secreción de Insulina , Células Secretoras de Insulina/efectos de los fármacos

RESUMEN

The in vitro effect of prolactin (PRL) on the growth and motility of Toxocara canis larvae was assessed. Additionally, the expression and location of prolactin receptors (PRL-Rs) were determined in the larvae. Larvae of T. canis were incubated with different concentrations of PRL for different periods of time. The stimulated larvae accelerated their enlargement and increased their motility. The mean percentage of PRL-R+ cells in non-stimulated larvae, measured by flow cytometry was 7.3±0.3%. Compared with non-stimulated larvae, the mean fluorescence intensity (p<0.05) increased in larvae incubated with 40ng/mL of PRL for 10 days. A 465-bp length fragment was amplified from larvae gDNA by PCR. The sequence of this fragment showed 99% similarity with the gene fragment that codes for the PRL-R of the domestic dog. A high concentration of PRL-Rs was immune-located in the posterior region of the larval intestine; therefore, the intestinal cells in this region were most likely the targets for this hormone. Based on these results, PRL-Rs were identified in T. canis larvae, and the in vitro stimulation with PRL increased the number of these receptors, accelerated the growth and modified the activity of larvae. All of the above suggest that T. canis larvae are evolutionarily adapted to recognize the PRL of their definitive host and furthermore might explain the reactivation of tissue-arrested larvae during the gestation of bitches, which does not occur in gestating females of other species.

Asunto(s)

Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Prolactina/farmacología , Receptores de Prolactina/metabolismo , Toxocara canis/efectos de los fármacos , Toxocara canis/fisiología , Toxocariasis/parasitología , Animales , Hormonas/farmacología , Técnicas In Vitro , Larva , Toxocara canis/genética , Toxocara canis/crecimiento & desarrollo

RESUMEN

Hormonal ovarian stimulation may affect transcripts in somatic cells of cumulus-oocyte complexes (COCs) and affect the resulting oocyte quality. Here, in parallel with morphological classification and in vitro maturation (IVM) rate analysis, we investigated the expression of hyaluronan synthase 2 (HAS2), gonadotropic receptors (FSHR and LHR) and connexin 43 (GJA1) in cumulus cells (CCs) from goat COCs after multi-dose FSH (MD) or one-shot FSH/eCG (OS) treatments, using bovine COCs as control groups. The MD treatment produced more large follicles, and the resulting COCs had a better morphology and IVM rate than were obtained with OS. The OS treatment produced COCs with increased HAS2, FSHR, LHR and GJA1 expression. This gene expression pattern was also observed in the CCs of COCs that showed poor morphological characteristics. On the other hand, the mRNA levels were more similar between groups after IVM; FSHR and LHR were the main genes that showed decreased expression. Some events that occurred in bovine CCs during IVM, such as cell expansion, increased HAS2 expression and decreased GJA1 expression, were less evident or did not occur in goat COCs. In conclusion, increasing HAS2, FSHR, LHR and GJA1 expression in goat COCs does not confer greater meiotic competence to oocytes. Instead, it may result from poor regulation of gene expression in CCs by lower quality oocytes. Finally, cumulus expansion, together with HAS2 upregulation and GJA1 downregulation, seems to be more important for bovine COCs than for goat COCs. Additional studies are needed to investigate the importance of other HAS isoforms and connexins in goat COCs.

Asunto(s)

Gonadotropina Coriónica/farmacología , Células del Cúmulo/enzimología , Hormona Folículo Estimulante/farmacología , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Glucuronosiltransferasa/metabolismo , Inducción de la Ovulación/veterinaria , Animales , Gonadotropina Coriónica/administración & dosificación , Células del Cúmulo/metabolismo , Combinación de Medicamentos , Femenino , Hormona Folículo Estimulante/administración & dosificación , Hormonas/administración & dosificación , Hormonas/farmacología , Sustancias para el Control de la Reproducción/administración & dosificación , Sustancias para el Control de la Reproducción/farmacología