Intrauterine growth restriction induced via placental insufficiency programs a significant increase in blood pressure at 12 months of age in female growth-restricted rats that is associated with early cessation of estrous cyclicity, indicative of premature reproductive senescence. In addition, female growth-restricted rats at 12 months of age exhibit a significant increase in circulating testos...

The proto-oncoprotein Cbl is known to control several signaling processes. It is highly expressed in the testis, and because spermatogenesis is androgen dependent, we investigated the androgen dependency expression of Cbl through its testicular sub-localization and its expression levels in rats that were exposed to the antiandrogen flutamide or were hypophysectomized. We report the androgen dep...

This review compares the tolerability profiles of the three currently available nonsteroidal antiandrogens, flutamide, bicalutamide and nilutamide. Pharmacological effects associated with blockade of the androgen receptor are frequent with all three drugs. Gynecomastia and breast pain are seen more frequently during antiandrogen monotherapy than during combination with medical or surgical castr...

The cytochrome P450 1B1 (CYP1B1) is involved in the metabolism of procarcinogens and xenobiotics. Human CYP1B1 protein has been detected in a variety of tumors but is not detected in adjacent normal tissues or in liver. This suggests that CYP1B1 could biotransform anticancer agents specifically in the target cells. The interaction between CYP1B1 and 12 commonly used anticancer drugs was screene...

Anovulation in women with polycystic ovary syndrome (PCOS) is the direct effect of high local androgen concentrations on the ovary. Antiandrogens are substances that prevent androgens from expressing their activity on target tissues. Flutamide is a nonsteroid antiandrogen that has been found effective in hirsute patients, although its mechanism of action is unclear. Eight girls, ranging in age ...

Once thought to be an artifact of microsomal systems, atypical kinetics with cytochrome P450 (CYP) enzymes have been extensively investigated in vitro and found to be substrate and species dependent. Building upon increasing reports of heterotropic CYP activation and inhibition in clinical settings, we screened a compound library of clinically approved drugs and various probe compounds to ident...

Although studies have shown that administration of testosterone receptor antagonist, flutamide, following trauma-hemorrhage, improves hepatic, cardiovascular, and immune functions, the precise cellular/molecular mechanisms responsible for producing these salutary effects remain largely unknown. To study this, male C3H/HeN mice were subjected to a midline laparotomy and hemorrhagic shock (35+/-5...

BACKGROUND Spinal bulbar muscular atrophy (SBMA) is caused by a CAG repeat expansion mutation in the androgen receptor (AR) gene, and mutant AR is presumed to act in motoneurons to cause SBMA. However, we found that mice overexpressing wild-type (wt) AR solely in skeletal muscle fibers display the same androgen-dependent disease phenotype as when mutant AR is broadly expressed, challenging the ...

Patients diagnosed as having benign prostatic hyperplasia (BPH) had determination of prostate volume (PV), prostate-specific antigen (PSA), and serum testosterone before consideration for entry into a double-blind, randomized trial of flutamide (750 mg/day for 6 months). The mean PSA level for these patients (N = 43) was 7.6 ng/ml (range: 1.0 to 45.7), and the mean PV was 76.8 cm3 (range: 24 to...

The role of prenatal androgen on the differentiation of sexually dimorphic juvenile play and adult copulatory patterns was evaluated in male offspring of rats injected with 5 mg of the androgen receptor blocker flutamide (4'-nitro-3'-trifluoromethylisobutyranilide) from Days 11-21 of pregnancy. Rough-and-tumble play was incompletely masculinized in flutamide-exposed males at 31 days of age. The...