RESUMO
Over a 15-year period, our university-based laboratory obtained 125 adrenal tumors, of which 15 (12%) were adrenal cortical carcinomas. Of these, 6 (40% of the carcinomas) occurred in patients with clear clinical manifestations of steroid hormone excess. Adrenal cortical carcinoma cells derived from the surgically resected tumors in 4 of these patients were isolated and established in primary culture. Radiotracer steroid interconversion studies were carried out with these cultures and also on mitochondria isolated from homogenized tissues. Large tumors had the lowest steroidogenic activities per weight, whereas small tumors had more moderately depressed enzyme activities relative to cells from normal glands. In incubations with pregnenolone as substrate, 1 mM metyrapone blocked the synthesis of corticosterone and cortisol and also the formation of aldosterone. Metyrapone inhibition was associated with a concomitant increase in the formation of androgens (androstenedione and testosterone) from pregnenolone. Administration of metyrapone in vivo before surgery in one patient resulted in a similar increase in plasma androstenedione, though plasma testosterone levels were not significantly affected. In cultures of two of four tumors examined, dibutyryl cAMP stimulated 11ss-hydroxylase activity modestly; ACTH also had a significant stimulatory effect in one of these tumors. Unlike results obtained with normal or adenomatous adrenal cortical tissues, mitochondria from carcinomatous cells showed a lack of support of either cholesterol side-chain cleavage enzyme complex or steroid 11ss-hydroxylase activity by Krebs cycle intermediates (10 mM isocitrate, succinate or malate). This finding is consistent with the concept that these carcinomas may tend to function predominantly in an anaerobic manner, rather than through the oxidation of Krebs cycle intermediates.
Assuntos
Corticosteroides/biossíntese , Neoplasias do Córtex Suprarrenal/metabolismo , Carcinoma/metabolismo , Corticosteroides/isolamento & purificação , Corticosteroides/metabolismo , Hormônio Adrenocorticotrópico/farmacologia , Aldosterona/sangue , Bucladesina/farmacologia , Técnicas de Cultura de Células , Ciclo do Ácido Cítrico , Desoxicorticosterona/metabolismo , Humanos , Metirapona/farmacologia , Mitocôndrias/metabolismo , Pregnenolona/metabolismo , Esteroide 11-beta-Hidroxilase/metabolismoRESUMO
PIP: Mexico and the US share a long border as well as strong cultural and economic ties. Mexico bought $25 billion worth of American goods in 1989. 1 million workers enter the labor market in Mexico every year. Mexico City is heavily polluted, 40% of the rural population is malnourished, and deforestation and desertification further damage the environment. Mexican real wages dropped 25% in the 1980s as oil prices declined. Egypt's arable land area is only 4% of the total, water supplies are scarce, but its human resources are abundant. 3 million Egyptians work overseas. The runaway population growth means that at the current rate it will double by 2012 from 50 million in 1990 threatening the stability of the country. Food production is off because of salinization caused by the Aswan Dam. Kenya has weathered droughts in the 1980s without major upheavals, but the softening of world coffee and tea prices, fears of European tourists, and more expensive imported oil have weakened the economy. The population doubled from 8 million in 1960 to 16 million in 1980 with a fertility rate of 8 children/woman. The prospect is 40 million by 2000 and 80 million by 2020. Deforestation caused by fuelwood needs has increased erosion resulting in reduced agricultural productivity. Agroforestry training and more energy efficiency are required, and water supplies are also insufficient. The Philippines uplands have experienced environmental degradation caused by population pressure: increase from 19 million in 1948 to 63 million in 1988. Since ownership of good cropland is concentrated in a few wealthy families landless people clear forests for cultivation leading to erosion. Logging also contributes to deforestation, but environmental destruction is not among government priorities.^ieng