RESUMO
White bodies (WB), multilobulated soft tissue that wraps the optic tracts and optic lobes, have been considered the hematopoietic organ of the cephalopods. Its glandular appearance and its lobular morphology suggest that different parts of the WB may perform different functions, but a detailed functional analysis of the octopus WB is lacking. The aim of this study is to describe the transcriptomic profile of WB to better understand its functions, with emphasis on the difference between sexes during reproductive events. Then, validation via qPCR was performed using different tissues to find out tissue-specific transcripts. High differentiation in signaling pathways was observed in the comparison of female and male transcriptomic profiles. For instance, the expression of genes involved in the androgen receptor-signaling pathway were detected only in males, whereas estrogen receptor showed higher expression in females. Highly expressed genes in males enriched oxidation-reduction and apoptotic processes, which are related to the immune response. On the other hand, expression of genes involved in replicative senescence and the response to cortisol were only detected in females. Moreover, the transcripts with higher expression in females enriched a wide variety of signaling pathways mediated by molecules like neuropeptides, integrins, MAPKs and receptors like TNF and Toll-like. In addition, these putative neuropeptide transcripts, showed higher expression in females' WB and were not detected in other analyzed tissues. These results suggest that the differentiation in signaling pathways in white bodies of O. maya influences the physiological dimorphism between females and males during the reproductive phase.
Assuntos
Octopodiformes/fisiologia , Reprodução/fisiologia , Transdução de Sinais , Transcriptoma , Proteínas Adaptadoras de Transdução de Sinal/fisiologia , Animais , Proteínas Argonautas/fisiologia , Diferenciação Celular , RNA Helicases DEAD-box/fisiologia , Estradiol Desidrogenases/fisiologia , Feminino , Perfilação da Expressão Gênica , Hidrocortisona/fisiologia , Sistema de Sinalização das MAP Quinases , Masculino , Proteínas de Membrana/fisiologia , Octopodiformes/genética , Filogenia , Receptores de Hormônio Liberador da Corticotropina/fisiologia , Receptores de Estrogênio/fisiologia , Fatores SexuaisRESUMO
Hydroxysteroid (17-beta) dehydrogenase 1 (HSD17B1) catalyzes the conversion between estrone (E1) and estradiol (E2). The reaction is reversible in vitro, but the data in cultured cells suggest that E2 production is the predominant reaction in physiological conditions. However, the hypothesis has not been verified in vivo. In the present study, estrogen-dependent MCF-7 human breast cancer cells were stably transfected with an expression plasmid for human HSD17B1. The enzyme efficiently converted E1 to E2 and enhanced the estrogen-dependent growth of cultured MCF-7 cells in the presence of hormonally less active E1. The HSD17B1-expressing cells also formed estrogen-dependent tumors in immunodeficient nude mice. After treating the mice with an appropriate dose of the substrate (E1, 0.1 micromol/kg x d), a marked difference in tumor growth was observed between nontransfected and HSD17B1-transfected MCF-7 cells, mean tumor weights at the end of E1 treatment being 23.2 and 130.4 mg, respectively. Furthermore, estrogen-dependent growth of the HSD17B1-expressing xenografts in the presence of E1 was markedly inhibited by administering 5 micromol/kg x d of a specific HSD17B1 inhibitor. After a 4-wk treatment, the tumor size was reduced by 59.8% as compared with the nontreated tumors, whereas the uterine growth of the mice was not affected by the HSD17B1 inhibitor used. This was in line with the induction of apoptosis of the tumors. The results evidently show that estrogenic response for E1 is enhanced by the local action of HSD17B1 in vivo, and thus, the enzyme is a potential target for pharmacological inhibition of estrogen action.
Assuntos
Estradiol Desidrogenases/fisiologia , Estrogênios/farmacologia , Neoplasias Mamárias Experimentais/enzimologia , Neoplasias Hormônio-Dependentes/enzimologia , Animais , Linhagem Celular Tumoral , Inibidores Enzimáticos/farmacologia , Estradiol Desidrogenases/antagonistas & inibidores , Receptor alfa de Estrogênio/fisiologia , Estrogênios/metabolismo , Feminino , Humanos , Neoplasias Mamárias Experimentais/tratamento farmacológico , Neoplasias Mamárias Experimentais/patologia , Camundongos , Camundongos Endogâmicos BALB C , Transplante de Neoplasias , Neoplasias Hormônio-Dependentes/tratamento farmacológico , Neoplasias Hormônio-Dependentes/patologia , Transplante HeterólogoRESUMO
Although there is a growing body of evidence that 17 beta-hydroxysteroid oxidoreductase plays a role in the regulation of steroid levels in epithelial tumors of the endometrium and breast, our knowledge of its role in other gynecologic tumors is limited. In this investigation, the 17 beta-hydroxysteroid oxidoreductase activity of cell lines derived from two ovarian tumors (OVCAR-3, CAOV-3) and an epidermoid tumor of the vulva (A431) was assayed under conditions which differentiate between 17 beta-hydroxysteroid oxidoreductase type 1, a cytosolic isoform highly specific for estradiol, and type 2, a membrane bound isoform reactive with both estradiol and testosterone. On the basis of estradiol/testosterone activity ratios, all three cell lines appear to have type 2-like activity, with the specific activity of A431 markedly greater than that of the other cell lines. Estradiol, progesterone, or EGF, alone or in combination, were without effect on the enzymatic activity of OVCAR-3 cells. EGF decreased the activity of CAOV-3 cells slightly. In contrast, EGF stimulated A431 17 beta-hydroxysteroid oxidoreductase activity 7-8-fold over a 5-day exposure. Estradiol or progesterone, singly or in combination, also did not effect the enzymatic activity of A431 cells. However, progesterone inhibited the increase in activity seen in the presence of EGF. With EGF, estradiol, and progesterone together, the increase in enzymatic activity was comparable to that with EGF alone. The effects of estradiol and progesterone appear to result from steroid actions following binding of EGF to low-affinity receptors on A431 cells.
Assuntos
Fator de Crescimento Epidérmico/farmacologia , Estradiol Desidrogenases/fisiologia , Estradiol/farmacologia , Progesterona/farmacologia , Útero/enzimologia , Estradiol Desidrogenases/efeitos dos fármacos , Feminino , Humanos , Modelos Biológicos , Células Tumorais CultivadasRESUMO
Data on the possibility of estrogens to regulate absorption of free fatty acids (FFA) during absorption of lipids in small intestine with associated estrogen-receptor interaction and changes in fatty acid-binding protein (FABP) levels are reported. In particular, characteristics of cytoplasmic estrogen receptors, estradiol metabolism, FABP levels and spectra of FFA in FABP fraction were studied in small intestinal mucosa of sexually mature and immature female rabbits, intact or after ovariectomy and estradiol dipropionate administration. The dissociation constants (Kd) and number of binding sites were determined in coordinates of Scatchard. FABP levels were demonstrated spectrophotometrically after ultracentrifugation (K-32M) and gel filtration (G-75). FFA composition of FABP fraction, chyme and enterocytes were analyzed by a chromatographic method (Tsvet-110). Levels of body estrogens were monitored by high-performance liquid chromatographic analysis (Tsvet-306) of estrogens in daily urine. The study has demonstrated a specific relation between FABP levels and their lipid component, FFA, on the one hand and endo- and exogenous estrogen levels on the other hand, in female rabbits maintained on a standard fat-free diet.