RESUMO
Gonadotropins exert their effect on ovarian follicular cells through the activation of the hormone sensitive adenylate cyclase and consequent elevation of intracellular cyclic AMP (cAMP). Desensitization to the hormone in cultured primary granulosa cells can occur within a short period and internalization of the hormone-receptor complex has been observed both in vivo and in vitro. It was recently documented that the gonadotropins as well as cAMP activate MAP kinase (MAPK) in granulosa cells. Moreover we discovered that specific inhibitors of extracellular signal-regulated kinase phosphorylation, 1 and 2, augment steroidogenesis in granulosa cells up-regulating steroidogenic acute regulatory (StAR) protein expression, and that this modulation is blocked by specific inhibitors of protein kinase A. It is therefore suggested that gonadotropins may activate both stimulatory and inhibitory pathways which regulate steroidogenesis. Moreover the ratio between the activity of these two pathways may determine the rate of steroidogenesis, and rapid activation of MAPK may account as part of the mechanism of desensitization to the hormonal action. Steroidogenic factor-1 and DAX-1 may be involved in the regulation of the MAPK-dependent attenuation of steroidogenesis, since they exhibit sites that could be potentially phosphorylated by the MAPK cascade.
Assuntos
Gonadotropinas Hipofisárias/farmacologia , Células da Granulosa/efeitos dos fármacos , Células da Granulosa/metabolismo , Animais , Células Cultivadas , AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Feminino , Expressão Gênica , Humanos , Técnicas In Vitro , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Fosfoproteínas/genética , Fosforilação , Ratos , Receptores do FSH/efeitos dos fármacos , Receptores do FSH/metabolismo , Esteroides/biossínteseRESUMO
Ocular metastases from carcinoid tumors are considered rare. They can be the primary presentation of a carcinoid tumor or develop during the course of the disease. The extent of distant metastases from carcinoid tumors correlates with poor prognosis and survival; early detection of metastasis may change the overall management. Radiopharmaceutical-labeled imaging techniques have been widely applied for the detection and localization of such lesions based on isotope uptake by neuroendocrine tumors. Routine application of these imaging modalities may reveal previously unsuspected lesions and may also be used to help stage the disease and to identify patients who may be treated with radiopharmaceuticals. Of 40 patients with carcinoid tumors reviewed in our department since we started routine scanning, we identified 6 (15%) who demonstrated ocular metastases: 5 with obvious lesions and 1 with presumed metastasis according to the results of nucleotide scanning. All 6 were negative on screening with [(123)I]meta-iodobenzylguanidine, whereas 3 of 4 who were screened with [(111)In]octreotide showed positive uptake. All patients responded well to radiotherapy and chemotherapy and did not require surgical treatment. The orbit and its contents appear to be a common site for carcinoid metastasis, and radiopharmaceutical imaging with labeled octreotide is useful in identifying many of these lesions.
Assuntos
3-Iodobenzilguanidina , Tumor Carcinoide/diagnóstico por imagem , Tumor Carcinoide/secundário , Neoplasias Oculares/diagnóstico por imagem , Neoplasias Oculares/secundário , Radioisótopos de Índio , Ácido Pentético , Compostos Radiofarmacêuticos , Adulto , Idoso , Idoso de 80 Anos ou mais , Tumor Carcinoide/patologia , Neoplasias Oculares/patologia , Feminino , Fundo de Olho , Humanos , Radioisótopos do Iodo , Masculino , Pessoa de Meia-Idade , Ácido Pentético/análogos & derivados , CintilografiaAssuntos
Glândulas Endócrinas/fisiologia , Proteínas de Neoplasias/fisiologia , Neuropeptídeos/fisiologia , Neoplasias da Próstata/etiologia , Carcinoma/etiologia , Carcinoma/metabolismo , Carcinoma/patologia , Divisão Celular , Progressão da Doença , Glândulas Endócrinas/citologia , Humanos , Masculino , Proteínas de Neoplasias/metabolismo , Neuropeptídeos/metabolismo , Próstata/citologia , Próstata/inervação , Próstata/fisiologia , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Testosterona/sangueRESUMO
Patients with acromegaly are at increased risk of colorectal neoplasia and, by analogy with high-risk nonacromegalic patients, may require regular colonoscopic screening. However, it is unknown whether the risk is equal in all patients or whether some should be regarded as carrying a particularly high risk. The aims of this study were: 1) to establish the natural history of colorectal neoplasia in acromegaly; 2) to establish which patients are at increased risk of developing neoplasia; and 3) to elucidate the influence of insulin-like growth factor I (IGF-I) in adenoma formation. A prospective colonoscopic evaluation of the development of new premalignant adenomas in the colon was performed in 66 patients with biochemically proven acromegaly who had previously undergone colonoscopic screening and removal of all visible polyps. Twenty-five patients (38%) had a total of 37 polyps detected at the second colonoscopy: nine (14%) had at least one adenoma, and 18 (27%) had one or more hyperplastic polyps (2 patients had both). The development of new adenomas, but not hyperplastic polyps, was associated both with elevated serum IGF-I (P < 0.005) and, to a lesser extent, with a previous adenoma at the original colonoscopy (P < 0.07). In summary, patients with acromegaly and in whom serum IGF-I remains elevated and/or who have had a previous adenoma should be regarded as having an especially high risk for the development of subsequent colorectal neoplasia. Serum IGF-I seems to be implicated in the development of colorectal neoplasia in acromegaly, although the exact mechanisms remain uncertain.