[Role of tumor necrosis factor alpha in atherosclerosis]. / Participación del factor de necrosis tumoral-alpha en la aterosclerosis.

We describe tumour necrosis factor alpha and its role in the development of the atherosclerotic lesion, and detail the effects of this cytokine upon vascular endothelial cells under normal and high risk conditions. We propose that TNF-alpha performs a central role in the progression of the lesion since, once the endothelial cell feedback regulatory mechanisms are altered, there is an increase in the microenvironment TNF-alpha concentration, which together with some of the already well known risk factors, generates an environment that favours and perpetuates the development of the atheromatous lesion.

Sertoli cell conditioned media modulate the androgen biosynthetic pathways in rat Leydig cell primary cultures.

Increasing evidence suggests the presence of local modulators that contribute to testicular function regulation in rats. The seminiferous tubules and Sertoli cell factors influence the steroidogenic activity of Leydig cells. Addition of Sertoli cell conditioned media to primary cultures of adult rat Leydig cells produces in a dose-dependent manner an inhibition of testosterone production with a concomitant decrease in the C21 delta 4-intermediates of the steroidogenic pathway, modifying the C21/C19 ratios in normal cells. The nature and mechanisms of action of this putative modulating activity are currently under study.

Steroid metabolism in theca externa cells from preovulatory follicles of domestic hen (Gallus domesticus).

The purpose of this study was to evaluate the ability of theca externa cells from preovulatory follicles of the domestic hen to metabolize tritiated steroid precursors. Theca externa cells were isolated from ovarian preovulatory follicles at three different developmental stages; F1 (35 mm), F3 (26 mm), and F5 (13 mm). Tritiated pregnenolone (P5), progesterone (P4), dehydroepiandrosterone (DHEA), androstenedione (A4), and testosterone (T) were employed as precursors and their metabolic products were evaluated after separation by thin-layer chromatography. The major metabolite of P5 by theca externa cells was 5-pregnen-3 beta, 20 beta-diol (F5, 47%; F3, 39%; and F1, 24%), but minimal quantities of P4 were detected. Progesterone metabolism yielded mainly 4-pregnen-20 beta-ol-3-one (F5, 52%; F3, 34%; and F1, 49%). When DHEA was used as precursor, A4 was produced in higher amounts (F5, 29%; F3, 23%; and F1, 11%) than estrone (E1) (F5, 1.5%; F3, 0.9%; and F1, 0.4%). Androstenedione was mainly transformed into E1 (F5, 11.9%; F3, 12.2%; and F1, 0.2%) but lower quantities of T and 17 beta-estradiol (E2) were found. Testosterone was actively transformed into A4 (F5, 50%; F3, 50%; and F1, 30%), but a low transformation to E2 (F5, 1.9%; F3, 1.7%; and F1, 1.4%) and E1 (F5, 2%; F3, 1%; and F1, 0.5%) was found. These results show that theca externa cells from preovulatory follicles of hen have enzymatic activities of 20 beta-reductase (from P5 and P4), 3 beta-hydroxysteroid dehydrogenase/5-4 isomerase (from P5 and DHEA), 17 beta-hydroxysteroid dehydrogenase (from A4 and T), and aromatase (from A4 and T). Furthermore, the enzyme activities decrease with follicular maturation, except for 20 beta-reductase which is constant. These data support the concept that theca externa cells have the ability to synthesize different steroids than reported in theca externa cells. In addition, since theca externa cells did not show the capacity to produce androgens but these steroids were aromatized to estrogens by these cells, it was suggested that the interaction between theca interna cells and theca externa cells occurs in vivo, thus supporting the multicellular theory for estrogen production.