Poly(ADP-ribosyl)ation of transcription factors and coregulators, mediated by the poly(ADP-ribose) polymerase PARP-1, has been emerging as an important epigenetic mechanism that controls transcriptional dynamics in response to diverse intraand extracellular signals. PARP-1 activity is also implicated in the regulation of mammalian lifespan. Herein we show that transcriptional down-regulation of androgen receptor (AR) in the aging rat liver and in oxidatively stressed hepatoma cells involves exchange of a PARP-1-associated, p/CAF-containing coactivator assembly for a p53-interacting, Groucho/TLE1-, and mSin3A-included corepressor complex at an age-and oxidant-responsive DNA element (age-dependent factor (ADF) element) in the AR promoter. The coregulator switch is mediated by B-Myb and c-Myb, which bind to the ADF element and physically associate with PARP-1 and the tumor suppressor p53. Heterogeneous nuclear ribonucleoprotein K, residing at the ADF element in association with PARP-1, may serve a platform role in stabilizing the activating complex. PARP-1 coactivated B-Myb-and c-Myb-mediated transactivation of the AR promoter, and p53 antagonized the B-Myb/c-Myb-induced AR promoter activation. PARP-1, heterogeneous nuclear ribonucleoprotein K, B-Myb, and c-Myb each serves as a positive regulator of cellular AR content, whereas p53 negatively regulates AR expression. Our results identify a shared, PARP-1-regulated sensing mechanism that coordinates transcriptional repression of AR during aging and in response to oxidative stress. This study may provide insights as to how advancing age and intracellular redox balance might influence androgen-regulated physiology.Diverse physiology, involving both reproductive and nonreproductive processes, is regulated by the androgen receptor (AR), 4 which is an inducible transcription factor and the transmitter of androgen signals to the nucleus. In the liver, AR influences a wide range of metabolic activities, especially those linked to glucose and lipid homeostasis, as evident from the deregulated liver metabolism in mice that have hepatocyte-specific AR deficiency (1), and those linked to steroid, drug, and nutrient metabolism, as evident from the AR/androgendependent regulation of hepatic phase I and phase II enzymes (2-4). A role for AR in liver carcinogenesis was initially recognized from the finding that testicular feminized (Tfm) mice, which lack functional AR, are resistant to liver cancer from carcinogen exposure (5). The male prevalence of liver cancer in humans (6) is attributed in part to the hepatic AR, which has been detected in clinical hepatocellular carcinoma at both initial and advanced stages of the disease (7). Increased AR expression from its transcriptional up-regulation occurs frequently in human prostate carcinoma (8). Therefore, it is important to delineate the regulatory factors that contribute to altered AR levels in response to a changing milieu of various AR-expressing tissues including the liver.In the rat liver, reduced AR expression during aging, r...