Inhibitory effects of pharmacological doses of melatonin on aromatase activity and expression in rat glioma cells

Melatonin exerts oncostatic effects on different kinds of neoplasias, especially on oestrogen-dependent tumours. Recently, it has been described that melatonin, on the basis of its antioxidant properties, inhibits the growth of glioma cells. Glioma cells express oestrogen receptors and have the ability to synthesise oestrogens from androgens. In the present study, we demonstrate that pharmacological concentrations of melatonin decreases the growth of C6 glioma cells and reduces the local biosynthesis of oestrogens, through the inhibition of aromatase, the enzyme that catalyses the conversion of androgens into oestrogens. These results are supported by three types of evidence. Firstly, melatonin counteracts the growth stimulatory effects of testosterone on glioma cells, which is dependent on the local synthesis of oestrogens from testosterone. Secondly, we found that melatonin reduces the aromatase activity of C6 cells, measured by the tritiated water release assay. Finally, by (RT)–PCR, we found that melatonin downregulates aromatase mRNA steady-state levels in these glioma cells. We conclude that melatonin inhibits the local production of oestrogens decreasing aromatase activity and expression. By analogy to the implications of aromatase in other forms of oestrogen-sensitive tumours, it is conceivable that the modulation of the aromatase by pharmacological melatonin may play a role in the growth of glioblastomas

Late Pleistocene echimyid rodents (Rodentia, Hystricognathi) from northern Brazil

ABSTRACT Echimyidae (spiny rats, tree rats and the coypu) is the most diverse family of extant South American hystricognath rodents (caviomorphs). Today, they live in tropical forests (Amazonian, coastal and Andean forests), occasionally in more open xeric habitats in the Cerrado and Caatinga of northern South America, and open areas across the southern portion of the continent (Myocastor). The Quaternary fossil record of this family remains poorly studied. Here, we describe the fossil echimyids found in karst deposits from southern Tocantins, northern Brazil. The analyzed specimens are assigned to Thrichomys sp., Makalata cf. didelphoides and Proechimys sp. This is the first time that a fossil of Makalata is reported. The Pleistocene record of echimyids from this area is represented by fragmentary remains, which hinders their determination at specific levels. The data reported here contributes to the understanding of the ancient diversity of rodents of this region, evidenced until now in other groups, such as the artiodactyls, cingulates, carnivores, marsupials, and squamate reptiles