Data/hora: 04/06/2024 04:16:56

Provedor de dados: | 56
País: | Brazil
Título: | Biosynthesis and metabolism of steroid hormones by human adrenal carcinomas
Autores: | Brown,J.W.; Fishman,L.M.
Data: | 2000-10-01
Ano: | 2000
Palavras-chave: | Adrenal carcinoma; Cell culture; Steroids; Metyrapone; Dibutyryl cAMP; ACTH; Krebs cycle intermediates.
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.
Tipo: | Info:eu-repo/semantics/article
Idioma: | Inglês
Identificador: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2000001000014
Editor: | Associação Brasileira de Divulgação Científica
Relação: | 10.1590/S0100-879X2000001000014
Formato: | text/html
Fonte: | Brazilian Journal of Medical and Biological Research  v.33 n.10 2000
Fonte: | info:eu-repo/semantics/openAccess