RESUMO
We analyzed histomorphometrical changes and blood vessel immunohistochemical staining of CD31, NOTCH1 and JAGGED1 in induced polycystic ovaries of immature female Wistar rats, as well as serum hormone levels. The rats were randomly divided into control (n=18) and treated (n=18) groups. Treated animals received intramuscularly testosteronenantat weekly (0.1mg/g). Controls received the same amount of ricinus oil. Rats were weighed daily. Control and treated subgroups (6 rats per subgroup) were subsequently sacrificed after 21, 28 and 35 days of treatment. In ovaries of treated rats we found large cystic follicles, thick stromal tissue, many atretic preantral follicles, no ovulation and a thinner granulosa cell layer. CD31 stained blood vessels in the theca layer were reduced, with reduced JAGGED1 and NOTCH1 immunostaining. In controls, preantral and antral follicles were larger than in the treated group. Treated animals showed statistically significant lower progesterone and higher testosterone levels. They gained more weight than controls. Reduced immunostaining for NOTCH1 and JAGGED1 of reduced blood vessels of the theca layer was found in all stages of folliculogenesis with a distinct reduction in cystic and atretic follicles. Our results provide evidence of intrinsic abnormality during all stages of folliculogenesis in polycystic ovaries and this may result from crosstalk between circulating gonadotropins and follicular angiogenesis.
Assuntos
Proteínas de Ligação ao Cálcio/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Proteínas de Membrana/metabolismo , Ovário/fisiopatologia , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Síndrome do Ovário Policístico/induzido quimicamente , Receptor Notch1/isolamento & purificação , Animais , Modelos Animais de Doenças , Feminino , Humanos , Imuno-Histoquímica , Proteína Jagged-1 , Ovário/irrigação sanguínea , Ovário/citologia , Síndrome do Ovário Policístico/irrigação sanguínea , Síndrome do Ovário Policístico/fisiopatologia , Ratos , Ratos Wistar , Proteínas Serrate-JaggedRESUMO
BACKGROUND: The central role of Notch signalling in T-cell development and oncogenesis raises the question of the importance of this pathway in cutaneous T-cell lymphomas. OBJECTIVES: To investigate the pattern of expression of Notch and its ligands, Jagged and Delta, in skin samples of primary cutaneous CD30+ lymphoproliferative disorders. METHODS: Immunohistochemistry of formalin-fixed, paraffin-embedded skin samples from 12 patients with lymphomatoid papulosis (LyP) and 11 patients with primary cutaneous anaplastic large cell lymphoma (ALCL). Immunofluorescence studies of fresh skin samples obtained from three patients with LyP and two patients with primary cutaneous ALCL. RESULTS: We identified single Notch1-positive cells or small clusters of atypical cells in LyP. Similarly, strongly positive Jagged1 cells tended to be localized in clusters. Primary cutaneous ALCL had higher expression of Notch1 and Jagged1 compared with LyP. Cells expressing Notch1 and Jagged1 were colocalized and a subset of cells expressed both the receptor and the ligand. The expression of the ligand Delta1 was low to undetectable in both types of lymphoproliferations. A subpopulation of lymphoma cells was found to coexpress Notch1 and activated Akt kinase. CONCLUSIONS: These results imply a potential role for the Notch signalling pathway in the pathogenesis of primary cutaneous CD30+ lymphoproliferative disorders and provide a rationale for the exploration of the activity of Notch antagonists in the therapy of these diseases.
