The direct inhibitory effect of dutasteride or finasteride on androgen receptor activity is cell line specific.
Neonatal hormone manipulations and the maintenance of perineal muscles and their motor neurones in Albino Swiss rats.
(74/97)Newborn female Albino Swiss rats received testosterone propionate, dihydrotestosterone benzoate or oestradiol benzoate for 4 days after birth. The neonatal administration of all three hormones maintained neurones of the spinal nucleus of bulbocavernosus (SNB) complex in adulthood at levels intermediate between those found in normal females (approximately 40 neurones) and those found in normal males (approximately 220 neurones). Dihydrotestosterone benzoate was the most effective treatment. Oestradiol benzoate, while as potent as testosterone propionate in maintaining SNB neurone numbers, could not maintain the perineal muscles which are their normal target. Dihydrotestosterone benzoate and testosterone propionate maintained both neurones and muscles. Newborn male Albino Swiss rats received either the aromatase inhibitor 4-OH-androstenedione, or the 5 alpha-reductase inhibitor aza-steroid 17 beta-N,N-diethylcarbamoyl-4-methyl-4-aza-5 alpha-androstan-3-one(4-MA). Only neonatal treatment with 4-MA led to reduced SNB neurone numbers in adulthood, but the reduction was modest (-16%). The results of the two experiments suggest that several hormones can maintain SNB neurone numbers in Albino Swiss rats, but that 5 alpha-reduced metabolites of testosterone may be particularly effective. (+info)
5alpha-reductase type 3 enzyme in benign and malignant prostate.
Preventive and therapeutic efficacy of finasteride and dutasteride in TRAMP mice.
Physiological effects of an antimycotic azasterol on cultures of Saccharomyces cerevisiae.
(77/97)The yeast Saccharomyces cerevisiae has been studied during cultivation with a naturally occurring antimycotic azasterol. At very low concentrations (1.0 to 10.0 ng/ml), where growth retardation is not observed, an unusual sterol, ergosta-8,14-dien-3beta-ol, accumulates in high concentrations. Upon removal of the azasterol from the culture, the 8,14-diene is converted to ergosterol. Much smaller amounts of another 8,14-sterol, but with an additional unsaturation, have also been observed. Total sterol accumulation is higher in cultures containing subinhibitory levels of the antimycotic agent than the amounts of normal sterol accumulation in control cultures. With between 10 and 100 ng of azasterol per ml a transitory cessation of growth is observed from which the culture is able to recover. At much higher concentrations growth inhibition and even cell lysis results. Competitive inhibition of sterol 24(28)methylene reductase is demonstrated. (+info)
Endocrine-responsive pancreatic carcinoma: steroid binding and cytotoxicity studies in human tumor cell lines.
(78/97)We have begun to investigate the steroid responsiveness of pancreatic cancer by comparing human (MiaPaCa, Colo-357, RWP-1, RWP-2) and rodent (AR42j) pancreatic tumor cell lines with cultured estrogen receptor-positive breast cancer cells (MCF-7, T47-D). The four human pancreatic tumors contain measurable levels of specific estradiol binding sites with dissociation constants (Kd) that range from 1 to 9 nM, in contrast to the higher-affinity binding sites measured in the breast cancer cells (Kd less than or equal to 1 nM). Growth of one pancreatic tumor line (MiaPaCa) is stimulated 40% above control by exposure to nanomolar concentrations of estradiol, suggesting that the estrogen receptor in these cells is functioning like that in MCF-7 and T47-D cells. Glucocorticoids (dexamethasone, hydrocortisone) and androgen (fluoxymesterone) stimulate proliferation of Colo-357 cells by as much as 30%. Paradoxically, glucocorticoids inhibit AR42j cells to less than 50% of control growth. Micromolar exposures of estrogen (17 beta-estradiol), antiestrogen (tamoxifen), antiandrogen (dehydroxyflutamide), progestins (progesterone, R5020, medroxyprogesterone acetate), and inhibitors of steroid-metabolizing enzymes (17 beta-N,N-diethylcarbamyl-4-methyl-4-aza-5 alpha-androstan-3-one, danazol) impair growth of these pancreatic tumors to varying degrees, and with little relationship to estrogen receptor content. In general, progestins are slightly more growth inhibiting to these pancreatic tumor lines than the other endocrine agents tested, including tamoxifen. Only the RWP-2 cells appear completely resistant to steroidal therapy, showing less than 25% growth inhibition with exposure to therapeutic concentrations (less than or equal to 2.5 microM) of these agents. Colo-357, MiaPaCa, and AR42j cells are most responsive to these endocrine agents, and their overall pattern of sensitivity suggests that the steroid-dependent growth-inhibitory mechanisms of some pancreatic carcinomas may involve both receptor antagonism and direct inhibition of steroidal oxidoreductases. 17 beta-N,N-Diethylcarbamyl-4-methyl-4-aza-5 alpha-androstan-3-one, a potent inhibitor of 5 alpha-reductase with minimal affinity for androgen receptor, inhibits growth of Colo-357 cells to less than 40% of control and also inhibits AR42j and MiaPaCa cells. Dehydroxyflutamide, a potent androgen receptor antagonist with no direct influence on 5 alpha-reductase activity, inhibits growth of MiaPaCa and AR42j cells but has no affect on Colo-357 growth.(ABSTRACT TRUNCATED AT 400 WORDS) (+info)
Mode of action of the azasteroid antibiotic 15-aza-24 methylene-d-homocholesta-8,14-dien-3 beta-ol in Ustilago maydis.
(79/97)Ustilago maydis sporidia treated with 0.1 mug of azasterol (15-aza-24-methylene-d-homocholesta-8,14-dien-3beta-ol) per ml appeared branched and vacuolated after 6 h of incubation. Sporidial multiplication, dry weight increase, and synthesis of protein, deoxyribonucleic acid, and ribonucleic acid were only slightly or moderately inhibited during the initial 3 h of incubation. An increase of free fatty acids was observed in lipid extracts of treated sporidia after incubation for 3 h or more. Ergosterol synthesis was completely inhibited within 1 h and there was a gradual decline of ergosterol content during 6 h which was accompanied by an accumulation of the sterol intermediate ergosta-8,14-dien-3beta-ol. The results indicate that toxicity of the azasterol results from specific inhibition of the reduction of the sterol C-14(15) double bond. A triarimol-tolerant strain of Cladosporium cucumerinum was tolerant to the azasterol, but an imazalil-tolerant strain of Aspergillus nidulans was not. (+info)
Antagonism of inhibitory amino acids by the steroid derivative RU5135.
(80/97)The steroid derivative RU5135 has been tested for its ability to antagonize glycine and the gamma-aminobutyric acid (GABA) analogue muscimol on isolated preparations of rat optic nerve and cuneate nucleus, respectively. On the cuneate nucleus, RU5135 antagonized muscimol in a competitive manner with a pA2 value of 8.31. RU5135 shared a common site of action with bicuculline that was separate from the picrotoxin site. On the optic nerve, RU5135 antagonized glycine with a pA2 of 7.67. It shared a common site of action with strychnine. (+info)