Showing papers on "Steroid biosynthesis published in 1985"

The interaction of representative members from two classes of antimycotics—the azoles and the allylamines—with cytochromes P-450 in steroidogenic tissues and liver

Abstract: 1. Spectrophotometric studies with ketoconazole, clotrimazole and miconazole show strong type-II interactions with several cytochromes P-450, particularly (Ks107M−1; pH 7.4; 25.C) with the 11β-hydroxylase of adrenal mitochondria, with the 17α/20 lyase of testis microsomes and with some forms of cytochromes P-450 of liver.2. A tight binding of the azoles also occurs to the reduced cytochromes, giving rise to an impeded CO binding to the haem iron.3. The binding of the azoles to 11β-hydroxylase and 17α/20 lyase is much tighter than the binding of endogenous substrates, and consequently inhibition of steroidogenesis will occur at these sites. The metabolism of xenobiotic substrates by the cytochromes P-450 of liver will also be severely impeded.4. In contrast, the allylamines naftifine and SF 86–327 are type-I substrates for a small portion of cytochromes P-450 of liver microsomes only and there is no spectral evidence for binding to the cytochromes P-450 involved in steroid biosynthesis.

Induction of Renin Activity by Gonadotropic Hormones in Cultured Leydig Tumor Cells

Abstract: The hormonal regulation of renin activity in cloned and cultured Leydig tumor cells (designated MA-10) was examined The treatment of Leydig cell cultures with bovine LH (bLH), hCG, or with (Bu)2cAMP elicited a dose- and time-dependent induction of renin activity and a concomitant increase in steroid biosynthesis The optimum concentration of hCG was 25 ng/ml, which caused an average 25-fold increase in renin activity compared to the control value bLH action was optimum at 75-100 ng/ml and induced an approximately 35-fold increase in renin activity The maximum inducible level of renin activity was attained after 8-9 h of hormone treatments The addition of progesterone (the major steroid product of the MA-10 cells) did not induce a significant increase in renin activity Treatment of MA-10 cells with epidermal growth factor also failed to produce any increase in renin activity The optimum concentration of (Bu)2cAMP was 800 microM for the induction of renin activity and caused an approximately 40-fold increase compared to the control value Renin activity induced by bLH, hCG, or (Bu)2cAMP was completely inhibited by mouse anti-renin antibody, indicating the specific nature of renin Upon withdrawal of (Bu)2cAMP from the culture medium, renin activity gradually declined to the control level, and with retreatment of these cultures with (Bu)2cAMP, a newly induced state of enzyme activity was resumed Indirectly, the role of new protein and RNA synthesis was examined during hormonal regulation of renin induction using protein and RNA synthesis inhibitors such as cycloheximide, puromycin, actinomycin D, or rifampicin Both protein and RNA synthesis inhibitors blocked the induction of renin activity in the presence of all three inducing agents, bLH, hCG, or (Bu)2cAMP The results provide evidence that the induction of renin activity is modulated by bLH, hCG, or (Bu)2cAMP and represent the de novo synthesis of enzyme molecules

Primary aldosteronism: treatment with trilostane.

Abstract: Trilostane, an inhibitor of the 3β-hydroxysteroid dehydrogenase enzyme sytem of steroid biosynthesis, was applied to 18 patients with primary aldosteronism (9 patients with adrenal adenoma, 9 patients

Steroid biosynthesis in turtle testes

Abstract: 1. 1. Testicular metabolism of radiolabelled substrates (pregnenolone, progesterone and androstenedione) was examined in two species of turtles, Pseudemys scripta and Sternotherus odoratus . 2. 2. Chemical methods (chromatography, derivative formation and crystallization) identified testosterone (in both species) and 5α-androstane-3β,17β-diol (in S. odoratus ) as major products. 3. 3. Tentative identifications were also made of 20β-hydroxypregn-4-en-3-one in both turtles. Chromatographic profiles indicated the presence of several other C 19 - and C 21 -steroids. 4. 4. In S. odoratus , changes in proportions of the two major C 19 -compounds (testosterone and the 5α-androstanediol) suggest a “switch” in the enzymatic pathways which resembles that associated with maturation in the rat. This enzymatic switch may be associated with the annual testicular cycle of the adult turtle.

Ultrastructural and immunohistochemical studies on the zona-reticularis cells of the adrenal cortex of normal and 3-methylcholanthrene-treated mice.

Abstract: The drug-metabolism activity of adrenocortical cells of normal and 3-methylcholanthrene (MC)-treated ddY mice were examined ultrastructurally and immunohistochemically. Immunoblot analyses performed prior to immunohistochemistry revealed the presence of a protein — possible equivalent to cytochrome P-450 found in the liver microsomes of MC-treated male rats — in the adrenal homogenate of MC-treated female mice. Immunohistochemistry demonstrated the presence of a cytochrome-P-450-like protein in the adrenal-cortical cells (especially in the zona-reticularis cells) of MC-treated female mice; at the same time, a remarkable increase in the amount of SER in these cells was observed by electron microscopy. These findings suggest that cells of the mouse adrenal gland, particularly those of the zona-reticularis, might participate not only in steroid biosynthesis but also in some sort of drug metabolism (detoxication). In addition, there might be a sex-related difference in ddY mice.