Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 26
Filtrar
1.
Ann Entomol Soc Am ; 113(6): 425-438, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33244354

RESUMO

Questing is a host-seeking behavior in which ticks ascend plants, extend their front legs, and wait poised for a chance to attach to a passing host. Hard ticks are ectoparasites of terrestrial vertebrates and because some species vector disease, they are among the most medically important of arthropod pests. All ixodid ticks require blood to survive and reproduce with the number of blood-hosts needed to complete their life cycle varying among species. The vast majority are three-host ticks requiring a different host for each developmental stage: larva, nymph, and adult. A few, including some of the most economically important species, are one-host ticks, that quest only in the larval stage. Questing is a rate-limiting behavior critical to tick survival and disease transmission. For the off-host larval stage, survival is highly dependent on ecological and physiological factors. Yet, off-host larval ecophysiology is often overlooked for the more obvious adult and nymphal tick-host interactions. This review summarizes the literature on ixodid larval questing with emphasis on how specific biotic and abiotic factors affect off-host survival.

2.
Cell Commun Signal ; 14(1): 25, 2016 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-27765041

RESUMO

BACKGROUND: ErbB2 Receptor Tyrosine Kinase 2 (ErbB2, HER2/Neu) is amplified in breast cancer and associated with poor prognosis. Growing evidence suggests interplay between ErbB2 and insulin-like growth factor (IGF) signaling. For example, ErbB2 inhibitors can block IGF-induced signaling while, conversely, IGF1R inhibitors can inhibit ErbB2 action. ErbB receptors can bind and phosphorylate insulin receptor substrates (IRS) and this may be critical for ErbB-mediated anti-estrogen resistance in breast cancer. Herein, we examined crosstalk between ErbB2 and IRSs using cancer cell lines and transgenic mouse models. METHODS: MMTV-ErbB2 and MMTV-IRS2 transgenic mice were crossed to create hemizygous MMTV-ErbB2/MMTV-IRS2 bigenic mice. Signaling crosstalk between ErbB2 and IRSs was examined in vitro by knockdown or overexpression followed by western blot analysis for downstream signaling intermediates and growth assays. RESULTS: A cross between MMTV-ErbB2 and MMTV-IRS2 mice demonstrated no enhancement of ErbB2 mediated mammary tumorigenesis or metastasis by elevated IRS2. Substantiating this, overexpression or knockdown of IRS1 or IRS2 in MMTV-ErbB2 mammary cancer cell lines had little effect upon ErbB2 signaling. Similar results were obtained in human mammary epithelial cells (MCF10A) and breast cancer cell lines. CONCLUSION: Despite previous evidence suggesting that ErbB receptors can bind and activate IRSs, our findings indicate that ErbB2 does not cooperate with the IRS pathway in these models to promote mammary tumorigenesis.


Assuntos
Neoplasias da Mama/metabolismo , Proteínas Substratos do Receptor de Insulina/metabolismo , Receptor ErbB-2/metabolismo , Animais , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Feminino , Humanos , Proteínas Substratos do Receptor de Insulina/genética , Células MCF-7 , Masculino , Camundongos , Metástase Neoplásica , Ligação Proteica , Receptor ErbB-2/genética , Transdução de Sinais
3.
BMC Cancer ; 11: 377, 2011 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-21867536

RESUMO

BACKGROUND: Epidemiological evidence suggests that moderately elevated levels of circulating insulin-like growth factor-I (IGF-I) are associated with increased risk of breast cancer in women. How circulating IGF-I may promote breast cancer incidence is unknown, however, increased IGF-I signaling is linked to trastuzumab resistance in ErbB2 positive breast cancer. Few models have directly examined the effect of moderately high levels of circulating IGF-I on breast cancer initiation and progression. The purpose of this study was to assess the ability of circulating IGF-I to independently initiate mammary tumorigenesis and/or accelerate the progression of ErbB2 mediated mammary tumor growth. METHODS: We crossed heterozygous TTR-IGF-I mice with heterozygous MMTV-ErbB2 mice to generate 4 different genotypes: TTR-IGF-I/MMTV-ErbB2 (bigenic), TTR-IGF-I only, MMTV-ErbB2 only, and wild type (wt). Virgin females were palpated twice a week and harvested when tumors reached 1000 mm(3). For study of normal development, blood and tissue were harvested at 4, 6 and 9 weeks of age in TTR-IGF-I and wt mice. RESULTS: TTR-IGF-I and TTR-IGF-I/ErbB2 bigenic mice showed a moderate 35% increase in circulating total IGF-I compared to ErbB2 and wt control mice. Elevation of circulating IGF-I had no effect upon pubertal mammary gland development. The transgenic increase in IGF-I alone wasn't sufficient to initiate mammary tumorigenesis. Elevated circulating IGF-I had no effect upon ErbB2-induced mammary tumorigenesis or metastasis, with median time to tumor formation being 30 wks and 33 wks in TTR-IGF-I/ErbB2 bigenic and ErbB2 mice respectively (p = 0.65). Levels of IGF-I in lysates from ErbB2/TTR-IGF-I tumors compared to ErbB2 was elevated in a similar manner to the circulating IGF-I, however, there was no effect on the rate of tumor growth (p = 0.23). There were no morphological differences in tumor type (solid adenocarcinomas) between bigenic and ErbB2 mammary glands. CONCLUSION: Using the first transgenic animal model to elevate circulating levels of IGF-I to those comparable to women at increased risk of breast cancer, we showed that moderately high levels of systemic IGF-I have no effect on pubertal mammary gland development, initiating mammary tumorigenesis or promoting ErbB2 driven mammary carcinogenesis. Our work suggests that ErbB2-induced mammary tumorigenesis is independent of the normal variation in circulating levels of IGF-I.


Assuntos
Transformação Celular Neoplásica/genética , Fator de Crescimento Insulin-Like I/metabolismo , Neoplasias Mamárias Experimentais/etiologia , Receptor ErbB-2/genética , Animais , Feminino , Regulação da Expressão Gênica , Fator de Crescimento Insulin-Like I/genética , Glândulas Mamárias Animais/metabolismo , Neoplasias Mamárias Experimentais/genética , Neoplasias Mamárias Experimentais/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Receptor ErbB-2/metabolismo , Transdução de Sinais , Transgenes
4.
Ticks Tick Borne Dis ; 11(1): 101317, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31722851

RESUMO

The cattle fever tick, Rhipicephalus annulatus (Say), is an economically destructive arthropod because of its ability to vector bovine babesiosis. Cattle fever ticks can spend more than 90% of their life cycle as questing larvae, but the effect of climatic factors on their off-host behavior and survival is unclear. The goal of this study was to measure the effects of specific ecological factors on off-host larvae in nature. The study was conducted in a south Texas pasture over a 20-mo period, during which time larval populations were surveyed and ambient weather variables - relative humidity and temperatures - were recorded. Oviposition success and larval survival varied between cattle fever tick cohorts and was affected by relative humidity and canopied (with tree cover) versus exposed habitat. The results show that relative humidity and the interaction of relative humidity and inhabiting canopied habitats play a key role in oviposition success. Additionally, canopied habitats have a positive influence on off-host larval survival in the spring and summer.


Assuntos
Clima , Ecossistema , Longevidade , Oviposição , Rhipicephalus/fisiologia , Animais , Larva/crescimento & desenvolvimento , Larva/fisiologia , Rhipicephalus/crescimento & desenvolvimento , Estações do Ano , Texas
5.
Dev Biol ; 313(1): 130-41, 2008 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-17996864

RESUMO

The tumor suppressor p53 is important for inhibiting the development of breast carcinomas. However, little is known about the effects of increased p53 activity on mammary gland development. Therefore, the effect of p53 dosage on mammary gland development was examined by utilizing the p53+/m mouse, a p53 mutant which exhibits increased wild-type p53 activity, increased tumor resistance, a shortened longevity, and a variety of accelerated aging phenotypes. Here we report that p53+/m virgin mice exhibit a defect in mammary gland ductal morphogenesis. Transplants of mammary epithelium into p53+/m recipient mice demonstrate decreased outgrowth of wild-type and p53+/m donor epithelium, suggesting systemic or stromal alterations in the p53+/m mouse. Supporting these data, p53+/m mice display decreased levels of serum IGF-1 and reduced IGF-1 signaling in virgin glands. The induction of pregnancy or treatment of p53+/m mice with estrogen, progesterone, estrogen and progesterone in combination, or IGF-1 stimulates ductal outgrowth, rescuing the p53+/m mammary phenotype. Serial mammary epithelium transplants demonstrate that p53+/m epithelium exhibits decreased transplant capabilities, suggesting early stem cell exhaustion. These data indicate that appropriate levels of p53 activity are important in regulating mammary gland ductal morphogenesis, in part through regulation of the IGF-1 pathway.


Assuntos
Envelhecimento , Glândulas Mamárias Animais/embriologia , Morfogênese , Proteína Supressora de Tumor p53/metabolismo , Animais , Feminino , Genes p53 , Fator de Crescimento Insulin-Like I/metabolismo , Glândulas Mamárias Animais/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Organismos Livres de Patógenos Específicos , Proteína Supressora de Tumor p53/genética
6.
Mol Cell Biol ; 26(24): 9302-14, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17030631

RESUMO

Insulin receptor substrates (IRSs) are signaling adaptors that play a major role in the metabolic and mitogenic actions of insulin and insulin-like growth factors. Reports have recently noted increased levels, or activity, of IRSs in many human cancers, and some have linked this to poor patient prognosis. We found that overexpressed IRS-1 was constitutively phosphorylated in vitro and in vivo and that transgenic mice overexpressing IRS-1 or IRS-2 in the mammary gland showed progressive mammary hyperplasia, tumorigenesis, and metastasis. Tumors showed extensive squamous differentiation, a phenotype commonly seen with activation of the canonical beta-catenin signaling pathway. Consistent with this, IRSs were found to bind beta-catenin in vitro and in vivo. IRS-induced tumorigenesis is unique, given that the IRSs are signaling adaptors with no intrinsic kinase activity, and this supports a growing literature indicating a role for IRSs in cancer. This study defines IRSs as oncogene proteins in vivo and provides new models to develop inhibitors against IRSs for anticancer therapy.


Assuntos
Peptídeos e Proteínas de Sinalização Intracelular/genética , Neoplasias Pulmonares/secundário , Neoplasias Mamárias Experimentais/genética , Fosfoproteínas/biossíntese , Fosfoproteínas/genética , Proteínas Adaptadoras de Transdução de Sinal/biossíntese , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Linhagem Celular Transformada , Feminino , Humanos , Hiperplasia , Proteínas Substratos do Receptor de Insulina , Peptídeos e Proteínas de Sinalização Intracelular/fisiologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Glândulas Mamárias Animais/patologia , Neoplasias Mamárias Experimentais/patologia , Camundongos , Camundongos Transgênicos , Metástase Neoplásica/genética , Metástase Neoplásica/patologia , Fosfoproteínas/fisiologia , Transdução de Sinais/fisiologia
7.
Front Biosci ; 13: 3273-87, 2008 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-18508432

RESUMO

The insulin-like growth factor (IGF) ligands stimulate cellular proliferation and survival by activating the type I insulin-like growth factor receptor (IGF-IR). As a result, the IGF signaling system is implicated in a number of cancers, including those of the breast, prostate, and lung. In addition to mitogenic and anti-apoptotic roles that may directly influence tumor development, IGF-IR also appears to be a critical determinant of response to numerous cancer therapies. This review describes the role of the IGF-IR pathway in mediating resistance to both general cytotoxic therapies, such as radiation and chemotherapy, and targeted therapies, such as tamoxifen and trastuzumab. It concludes with a description of approaches to target IGF-IR and argues that inhibition of IGF signaling, in conjunction with standard therapies, may enhance the response of cancer cells to multiple modalities.


Assuntos
Antineoplásicos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Neoplasias/tratamento farmacológico , Neoplasias/radioterapia , Receptor IGF Tipo 1/fisiologia , Neoplasias da Mama/terapia , Estradiol/análogos & derivados , Estradiol/uso terapêutico , Feminino , Fulvestranto , Humanos , Masculino , Neoplasias da Próstata/terapia , Cloridrato de Raloxifeno/uso terapêutico , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Transdução de Sinais , Resultado do Tratamento
8.
Vet Sci ; 5(2)2018 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-29570655

RESUMO

The cattle tick, Rhipicephalus microplus (Canestrini), is an economically destructive arthropod because of its ability to vector bovine babesiosis. It is known that cattle ticks can spend 80-90% of their lifecycle as questing larvae, yet the effect of climatic factors on their off-host behavior and survival is unclear. The goal of this study was to measure the effects of specific ecological factors on off-host questing larvae in nature. The study was conducted in a south Texas pasture over a two-year period, during which time larval populations were surveyed. Simultaneously, weather variables-precipitation, relative humidity, and ambient temperatures-were recorded. Larval survival rates varied among seasons, with the overall highest populations recorded in the spring and the lowest in the fall by a ratio of 20:1. In the winter, the larger numbers were collected from exposed habitats at a ratio of 6:1. Conversely, canopied habitats in the summer had 10-fold larger larval numbers. In the spring, exposed and canopied habitats showed no difference in tick larval survival rates. The results show that the interaction between season and habitat strongly influence off-host questing tick survival. Relative humidity was a key weather variable.

9.
Endocrinology ; 147(8): 3877-88, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16709615

RESUMO

The precise role of circulating IGF-I in somatic growth under normal and GH-deficient conditions remains unclear. To define the contribution of circulating IGF-I to the endocrine regulation of somatic growth and the GH/IGF-I axis, we constructed a transgene with the transthyretin (TTR) enhancer/promoter and the mouse IGF-I cDNA and generated TTR-IGF-I transgenic mice. The transgene was exclusively expressed in the liver, which resulted in a 50-60% increase in serum IGF-I, a decrease in serum GH, and an improved tolerance to glucose challenge. The body weight and lean mass of TTR-IGF-I mice were heavier compared with wild-type (WT) mice. The increase in lean mass was a result of increase in both number and thickness of skeletal muscle fibers. The femur, tibia, and body lengths of TTR-IGF-I mice also were longer. In WT mice, the GH antagonist pegvisomant (Peg) suppressed the transcription of endogenous IGF-I and acid-labile subunit (ALS) genes with no effect on IGF-binding protein 3 (IGFBP-3) mRNA. Consequently, Peg-induced GH deficiency in WT mice severely reduced ALS, IGF-I, and IGFBP-3 in the circulation and caused a severe growth deficit. In TTR-IGF-I mice, Peg reduced the mRNA of the endogenous IGF-I gene with no effect on the TTR-IGF-I transgene expression, leading to a blunted decrease in serum IGF-I levels. Interestingly, IGFBP-3 mRNA was elevated and circulating IGFBP-3 was less reduced in Peg-treated TTR-IGF-I mice. Peg-treated TTR-IGF-I mice also exhibited heavier body weight and longer body length than Peg-treated WT mice. Therefore, liver-expressed IGF-I can stimulate IGFBP-3 mRNA expression and stabilize IGFBP-3 under GH deficiency, leading to a better maintenance of IGF-I levels in the circulation. Higher circulating levels of IGF-I can stimulate somatic growth and lean mass and improve glucose tolerance.


Assuntos
Transtornos do Crescimento/fisiopatologia , Hormônio do Crescimento/deficiência , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/metabolismo , Fígado/fisiologia , Animais , Peso Corporal , Osso e Ossos/anatomia & histologia , Feminino , Expressão Gênica/fisiologia , Teste de Tolerância a Glucose , Transtornos do Crescimento/induzido quimicamente , Transtornos do Crescimento/prevenção & controle , Hormônio do Crescimento/sangue , Hormônio do Crescimento Humano/análogos & derivados , Hormônio do Crescimento Humano/farmacologia , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Especificidade de Órgãos , Pré-Albumina/genética , Gravidez , RNA Mensageiro/metabolismo , Transcrição Gênica/fisiologia
10.
Reprod Toxicol ; 21(1): 104-9, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16153799

RESUMO

Because prepubertal female rats maternally exposed to lead (Pb) exhibit suppressed serum levels of insulin-like growth factor-1 (IGF-1) and delayed puberty, we investigated the ability of centrally administered IGF-1 to stimulate luteinizing hormone (LH) release in vivo and LH-releasing hormone (LHRH) release in vitro from maternally Pb-exposed prepubertal female rats. Additionally, we assessed whether IGF-1 replacement could affect the timing of female puberty. Results demonstrated that IGF-1 stimulated significantly LH release in both control and Pb-exposed animals. When median eminences from control and Pb-exposed females were incubated with rat IGF-1 in vitro, they responded similarly with significant peptide-induced LHRH release. Lastly, we showed IGF-1 replacement reversed the delay in puberty caused by Pb. These results indicate the central LHRH response to IGF-1 is intact and that Pb-induced delayed puberty is due, at least in part, to suppressed circulating IGF-1 available to the hypothalamus.


Assuntos
Fator de Crescimento Insulin-Like I/farmacologia , Chumbo/toxicidade , Troca Materno-Fetal , Puberdade Tardia/induzido quimicamente , Animais , Feminino , Hormônio Liberador de Gonadotropina/metabolismo , Chumbo/sangue , Hormônio Luteinizante/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Puberdade Tardia/metabolismo , Ratos , Ratos Endogâmicos F344
11.
Cancer Prev Res (Phila) ; 8(10): 1000-9, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26290394

RESUMO

The most effective natural prevention against breast cancer is an early first full-term pregnancy. Understanding how the protective effect is elicited will inform the development of new prevention strategies. To better understand the role of epigenetics in long-term protection, we investigated parity-induced DNA methylation in the mammary gland. FVB mice were bred or remained nulliparous and mammary glands harvested immediately after involution (early) or 6.5 months following involution (late), allowing identification of both transient and persistent changes. Targeted DNA methylation (109 Mb of Ensemble regulatory features) analysis was performed using the SureSelectXT Mouse Methyl-seq assay and massively parallel sequencing. Two hundred sixty-nine genes were hypermethylated and 128 hypomethylated persistently at both the early and late time points. Pathway analysis of the persistently differentially methylated genes revealed Igf1r to be central to one of the top identified signaling networks, and Igf1r itself was one of the most significantly hypermethylated genes. Hypermethylation of Igf1r in the parous mammary gland was associated with a reduction of Igf1r mRNA expression. These data suggest that the IGF pathway is regulated at multiple levels during pregnancy and that its modification might be critical in the protective role of pregnancy. This supports the approach of lowering IGF action for prevention of breast cancer, a concept that is currently being tested clinically.


Assuntos
Metilação de DNA/genética , Glândulas Mamárias Animais/metabolismo , Paridade/genética , Receptor IGF Tipo 1/genética , Animais , Neoplasias da Mama/genética , Feminino , Genoma , Camundongos , Parto , Reação em Cadeia da Polimerase , Gravidez
12.
Endocrinology ; 145(10): 4558-64, 2004 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-15217984

RESUMO

We determined whether the effect of alcohol (ALC) to suppress LH secretion in immature female monkeys is due to a hypothalamic or pituitary site of action. Beginning at 20 months of age, four monkeys received a single intragastric dose of ALC (2.4 g/kg), and four monkeys received an equal volume of a saline/sucrose solution daily until they were 36 months old. For the hypothalamic response test, two basal samples (3.5 ml) were collected at 15-min intervals via the saphenous vein, and then N-methyl-D-L-aspartic acid (NMA; 20 mg/kg) was given iv and four more blood samples collected. Three weeks later, this protocol was repeated except LH-releasing hormone (LHRH) (5 microg/kg) was used to test pituitary responsiveness. NMA or LHRH was administered 3 h after the ALC. After the pituitary challenge, each monkey was ovariectomized and 6 wk later, implanted with an indwelling subclavian vein catheter. Blood samples were drawn every 10 min for 8 h to assess effects of ALC on post-ovariectomy LH levels and the profile of LH pulsatile secretion. The hypothalamic challenge showed NMA stimulated LH release in control monkeys, an action that was blocked by ALC. The pituitary challenge revealed that LHRH stimulated LH release equally well in control and ALC-treated monkeys. A post-ovariectomy rise in LH was observed in both groups, but levels were 45% lower in ALC-treated monkeys. This reduction was attributed to an ALC-induced suppression of both baseline and amplitude of pulses. Results demonstrate that the ALC-induced suppression of LH in immature female rhesus monkeys is due to an inhibitory action of the drug at the hypothalamic level.


Assuntos
Etanol/farmacologia , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Hormônio Luteinizante/antagonistas & inibidores , Animais , Feminino , Hormônio Liberador de Gonadotropina/farmacologia , Hormônio Luteinizante/metabolismo , Macaca mulatta , N-Metilaspartato/farmacologia , Ovariectomia , Hipófise/efeitos dos fármacos , Hipófise/metabolismo , Fluxo Pulsátil
13.
Toxicol Sci ; 77(1): 35-40, 2004 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-14514953

RESUMO

Estradiol (E2) is suppressed in prepubertal females exposed maternally to lead (Pb); thus, we assessed effects of Pb on ovarian steroidogenic acute regulatory protein (StAR) as a potential mechanism for this action. Adult Fisher 344 females were dosed with 12 mg of lead acetate per ml of Pb acetate (PbAc) or sodium acetate (NaAc; control), beginning 30 days prior to breeding and continuing until their pups were weaned. For the first part of this study, animals from both groups were killed when 31 days old, at 0800 h, for assessment of basal ovarian StAR gene expression. Results indicated Pb decreased (p < 0.01) both StAR transcripts. In the second part of the study, pregnant mare serum gonadotropin (PMSG) was administered to half of the Pb-treated and control animals at 0800 h. These animals, and animals from both groups that did not receive PMSG, were killed and ovaries and blood collected at 1600 h to assess ovarian StAR protein and E2 responsiveness to gonadotropin stimulation. Pb decreased (p < 0.0001) basal StAR protein expression and lowered (p < 0.001) E2 levels in animals that did not receive PMSG. PMSG induced (p < 0.0001) StAR protein in both the Pb-treated and control animals, an action associated with increased (p < 0.001) serum levels of E2. These results are the first to show that Pb alters basal StAR synthesis, but does not alter gonadotropin-stimulated StAR synthesis, hence, suggesting the primary action of Pb to suppress E2 is through its known action to suppress the serum levels of luteinizing hormone and not due to decreased responsiveness of StAR synthesizing machinery.


Assuntos
Compostos Organometálicos/toxicidade , Ovário/efeitos dos fármacos , Fosfoproteínas/metabolismo , Animais , Northern Blotting , Relação Dose-Resposta a Droga , Estradiol/sangue , Feminino , Expressão Gênica/efeitos dos fármacos , Gonadotropinas Equinas/farmacologia , Exposição Materna , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Compostos Organometálicos/análise , Ovário/metabolismo , Fosfoproteínas/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Endogâmicos F344 , Maturidade Sexual/efeitos dos fármacos , Maturidade Sexual/fisiologia
14.
Brain Res ; 1013(1): 91-7, 2004 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-15196971

RESUMO

Several studies suggest an interrelationship between estradiol (E2) and insulin-like growth factor-1 (IGF-1) at the hypothalamic level. The present study was designed to discern if the capability of IGF-1 to release LH and influence the timing of female puberty is influenced by E2. Twenty-eight-day-old female rats were ovariectomized (OVEX), then implanted with a third ventricular (3V) cannula. Two weeks later, these animals received subcutaneous (s.c.) injection of oil, or either one or two injections of E2 in the form of estradiol benzoate (1 microg). Forty-eight hours later, four basal blood samples were drawn then the animals received IGF-1 (200 ng) or saline via the 3V and four more blood samples were taken. Results indicated that E2 replacement lowered basal LH levels and IGF-1 induced a significant LH release in only animals that had E2 levels above 20 pg/ml. These levels of E2 were also associated with increases (p<0.05) in the expression of both IGF-1 receptor (IGF-1R) mRNA and protein. In order to further support the hypothesis that the action of IGF-1 at the time of puberty is influenced by E2, 24-day-old intact female rats received s.c. injection of sesame oil or 0.1 microg of E2. The next day, the E2-treated animals also received twice daily s.c. injections of either IGF-1 (500 ng) or saline until vaginal opening (VO) occurred. The animals that received E2 plus IGF-1 showed VO at 31.1 days, which was 2.5 days earlier (p<0.01) than E2-treated animals and 4 days earlier (p<0.001) than IGF-1-treated and saline control animals. Taken together, these results indicate that the hypothalamic action of IGF-1 to stimulate LH release and advance female pubertal development is dependent upon the influence of E2.


Assuntos
Estradiol/farmacologia , Fator de Crescimento Insulin-Like I/farmacologia , Hormônio Luteinizante/metabolismo , Receptores de Somatomedina/biossíntese , Animais , Feminino , Ovariectomia , Ratos , Ratos Sprague-Dawley , Receptores de Somatomedina/agonistas
15.
Life Sci ; 74(9): 1139-48, 2004 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-14687654

RESUMO

Studies using both Fisher 344 and Sprague-Dawley (SD) rat lines have shown that gestational and/or lactational maternal lead (Pb) exposure causes delayed reproductive maturation in their respective female offspring. Because these studies utilized different experimental regimens for dosing and for monitoring Pb levels, it has not been possible to determine which rat line provides the best model for low level Pb toxicity studies. This study was designed to address this issue. Adult Fisher and SD female rats were dosed with either a solution of PbAc containing 12 mg of Pb/ml or sodium acetate (NaAc) for controls. Dosing began 30 days prior to breeding and continued until their pups were weaned at 21 days of age. At the time of breeding and through weaning the blood lead (BPb) levels in the Fisher dams averaged 37.3 microg/dl and the SD dams averaged 29.9 microg/dl. Pb delayed the timing of puberty (p < 0.01) in Fisher offspring, and suppressed serum levels of luteinizing hormone (LH, p < 0.001) and estradiol (E2, p < 0.01). These effects did not occur in the SD offspring. Doubling the dose given to the SD rats increased their BPb levels to 62.6 microg/dl, yet there were still no effects noted. These results indicate that Fisher offspring are more sensitive to maternal Pb exposure with regard to puberty related insults than are SD rats, suggesting that the Fisher line may be a more reliable rodent model to study the effects of low level Pb toxicity.


Assuntos
Chumbo/toxicidade , Exposição Materna , Maturidade Sexual/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Feminino , Lactação , Chumbo/sangue , Gravidez , Radioimunoensaio , Ratos , Ratos Endogâmicos F344 , Ratos Sprague-Dawley , Testes de Toxicidade Crônica
16.
Reprod Toxicol ; 16(4): 343-52, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12220594

RESUMO

Lead (Pb) can delay sexual maturation; however, the mechanism and critical time of insult are not clearly defined. Therefore, we assessed maternal Pb levels during low-level gestational and/or lactational exposure, as well as blood and tissue Pb in developing fetuses in relation to the subsequent detrimental effects of Pb on puberty-related hormones and the onset of female puberty. Adult Fisher 344 female rats were gavaged daily with either a 1-ml solution of PbAc containing 12 mg/ml Pb or an equal volume of sodium acetate (NaCl), for the controls, from 30 days prior to breeding until their pups were weaned at 21 days. By cross-fostering at the time of birth, the pups were either exposed to PbAc or NaAc during gestation only, lactation only, or during both gestation and lactation. Pb delayed the timing of puberty and this delay was associated with suppressed serum levels of insulin-like growth factor-1 (IGF-1), luteinizing hormone (LH), and estradiol (E(2)). Liver IGF-1 mRNA was not affected, suggesting that Pb altered translation and/or secretion of IGF-1. We reported previously that peripherally derived IGF-1 acts at the hypothalamic level to facilitate LH release at puberty; hence, we suggest that the action of Pb in decreasing circulating IGF-1 contributes to the delayed puberty. The detrimental effects occurred regardless of the developmental time of exposure, although gestational exposure appeared more sensitive to the effects of Pb. Also, the effects noted were with blood Pb levels less than previously reported and these levels are relevant to human health concerns.


Assuntos
Lactação/efeitos dos fármacos , Intoxicação por Chumbo , Compostos Organometálicos/toxicidade , Efeitos Tardios da Exposição Pré-Natal , Maturidade Sexual/efeitos dos fármacos , Administração Oral , Animais , Animais Lactentes , Encéfalo/crescimento & desenvolvimento , Encéfalo/metabolismo , Estradiol/sangue , Estradiol/genética , Feminino , Fator de Crescimento Insulin-Like I/análise , Hormônio Luteinizante/sangue , Compostos Organometálicos/administração & dosagem , Compostos Organometálicos/farmacocinética , Gravidez , RNA Mensageiro/biossíntese , Ratos , Ratos Endogâmicos F344
17.
Discoveries (Craiova) ; 2(2): e15, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-26539561

RESUMO

The bZIP transcription factor NFIL3 (Nuclear factor Interleukin 3 regulated, also known as E4 binding protein 4, E4BP4) regulates diverse biological processes from circadian rhythm to cellular viability. Recently, a host of novel roles have been identified for NFIL3 in immunological signal transduction, cancer, aging and metabolism. Elucidating the signaling pathways that are impacted by NFIL3 and the regulatory mechanisms that it targets, inhibits or activates will be critical for developing a clearer picture of its physiological roles in disease and normal processes. This review will discuss the recent advances and emerging issues regarding NFIL3-mediated transcriptional regulation of CEBPß and FOXO1 activated genes and signal transduction.

18.
BMC Res Notes ; 7: 543, 2014 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-25134718

RESUMO

BACKGROUND: Epidemiological studies have shown that consumption of a high-fat diet (HFD) increases the risk of developing breast cancer (BC). Studies in rodents have shown HFD causes changes in the genetic programming of the maturing mammary gland (MG) increasing the susceptibility of developing the disease. Less is known about how HFD induced genes impact BC development. HFD exposure two weeks before conception to six weeks of age was previously shown to dramatically change MG gene expression in 10 week old mice. Therefore, we investigated these differentially expressed HFD-induced genes for their expression in BC using the NKI 295 breast tumor dataset. RESULTS: To examine the potential role of HFD induced genes in BC, we first investigated whether these HFD-induced genes in mouse MGs were differentially expressed in different types of human BC. Of the 28 HFD induced genes that were differentially expressed between BC subtypes in the NKI set, 79% were significantly higher in basal-like BC. Next, we analyzed whether HFD induced genes were associated with BC prognosis utilizing gene expression and survival data for each HFD induced gene from the NKI data and constructed Kaplan Meier survival plots. Significantly, 93% of the prognosis associated genes (13/14) were associated with poor prognosis (P = 0.002). Kaplan Meier analysis with 249 non-basal-like BC found that all but one of the genes examined were still significantly associated with poor prognosis. Furthermore, gene set enrichment analysis (GSEA) with HFD microarray data revealed that invasive BC genes where enriched in HFD samples that also had lost expression of luminal genes. CONCLUSIONS: HFD exposed mouse MGs maintain differential expression of genes that are found highly expressed in basal-like breast cancer. These HFD-induced genes associate with poor survival in numerous BC subtypes, making them more likely to directly impact prognosis. Furthermore, HFD exposure leads to a loss in the expression of luminal genes and a gain in expression of mesenchymal and BC invasion genes in MGs. Collectively, our study suggests that HFD exposure during development induces genes associated with poor prognosis, thus identifying how HFD diet may regulate BC development.


Assuntos
Neoplasias da Mama/genética , Dieta Hiperlipídica , Regulação da Expressão Gênica , Neoplasias da Mama/patologia , Feminino , Humanos , Invasividade Neoplásica , Prognóstico
19.
Exp Biol Med (Maywood) ; 239(7): 871-882, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24845367

RESUMO

Evidence suggests that environmental substances regulating estrogenic pathways during puberty may be detrimental to the developing mammary gland (MG). Manganese (Mn) is a trace mineral required for normal physiological processes. Prepubertal exposure to Mn induces precocious puberty in rats, an event associated with early elevations in puberty-related hormones, including estradiol (E2). However, until now the effect of Mn-induced precocious MG development has not been determined. Therefore, we assessed the ability of prepubertal Mn exposure to advance normal MG development and alter E2 driven pathways involved in tumorigenesis. Sprague Dawley female rats were gavaged daily with either 10 mg/kg manganese chloride (MnCl2) or saline (control) from postnatal day (PND) 12 through PND 30. Blood and MGs were collected on PNDs 30 and 120. Compared to controls, serum E2 levels on PND 30 were elevated (p < 0.05) in the Mn-treated group. Mn exposure significantly increased differentiated MG terminal ductal structures and the percentage of MG epithelial cells that stained positive for the proliferative marker, Ki67, at PND 30 (p < 0.001) and PND 120 (p < 0.001). Levels of Mn (ppm) were not elevated in these MGs. Mn-treated animals (40%) exhibited reactive stroma and intra-luminal focal hyperplasia in hemotoxylin and eosin stained MGs at PND 120. Furthermore, Mn exposure resulted in elevated protein expression levels of estrogen receptor α, activator protein 2α, phosphorylated (p)-Akt, and p53 in MGs on PND 120, but not on PND 30. Collectively, these data show that exposure to a supplemental dose of Mn causes accelerated pubertal MG growth which can progress to adult hyperplasia; thus, providing evidence that early life Mn exposure may increase susceptibility to breast cancer.

20.
Reprod Toxicol ; 44: 41-9, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24090629

RESUMO

Arsenic (As) is a prevalent environmental toxin readily accessible for human consumption and has been identified as an endocrine disruptor. However, it is not known what impact As has on female sexual maturation. Therefore, in the present study, we investigated the effects of prepubertal exposure on mammary gland development and pubertal onset in female rats. Results showed that prepubertal exposure to 10 mg/kg of arsenite (As(III)) delayed vaginal opening (VO) and prepubertal mammary gland maturation. We determined that As accumulates in the liver, disrupts hepatocyte function and suppresses serum levels of the puberty related hormone insulin-like growth factor 1 (IGF-1) in prepubertal animals. Overall, this is the first study to show that prepubertal exposure to As(III) acts peripherally to suppress circulating levels of IGF-1 resulting in delayed sexual maturation. Furthermore, this study identifies a critical window of increased susceptibility to As(III) that may have a lasting impact on female reproductive function.


Assuntos
Arsenitos/toxicidade , Poluentes Ambientais/toxicidade , Fator de Crescimento Insulin-Like I/antagonistas & inibidores , Maturidade Sexual/efeitos dos fármacos , Animais , Estradiol/sangue , Feminino , Hormônio do Crescimento/sangue , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Fígado/efeitos dos fármacos , Fígado/patologia , Hormônio Luteinizante/sangue , Glândulas Mamárias Animais/efeitos dos fármacos , Glândulas Mamárias Animais/crescimento & desenvolvimento , Troca Materno-Fetal , Gravidez , Ratos Sprague-Dawley , Maturidade Sexual/fisiologia
SELEÇÃO DE REFERÊNCIAS
Detalhe da pesquisa