Association states of androgen receptors in nuclei of human benign hypertrophic prostate

Abstract

Androgen receptors (AR) were quantified in nuclei purified from unfractionated benign hypertrophic prostate (bph) tissue and from separated epithelium and stroma from bph specimens. Both epithelial and stromal cell nuclei contained AR, although concentrations in epithelial cell nuclei were higher and more variable. Variations in AR levels in epithelial cell nuclei reflected variations in unfractionated-tissue nuclei. Nuclear AR were further characterized regarding extractability with or resistance to 0.6 mol/lKCl and micrococcal nuclease. Nuclei from unfractionated tissue, epithelium, and stroma contained populations of AR susceptible and refractory to solubilization with KC1 and nuclease. Nuclease- and salt-sensitive populations of AR were similar numerically. The observed variability in epithelial cell nuclear AR was attributable to a wide range of solubilizable AR. Nuclease-digestion profiles and sedimentation analyses revealed that this wide range was not due to AR associated with soluble chromatin oligomers but to AR not detectably associated with other nuclear components. In contrast, AR in stromal cell nuclei was predominantly resistant to KC1 and nuclease, and variability in total nuclear AR concentration was due to variation in the nonextractable population.

Alcohol Consumption, Cigarette Smoking, and Risk of Benign Prostatic Hyperplasia

“…Androgens play a role in the development and maintenance of BPH particularly in the prostatic epithelium, which is supported by androgen receptor expression in prostatic epithelium (34,35), reduction in hyperplastic prostate mass, primarily of the epithelium, with androgen deprivation (36), and the absence of BPH in men who are castrated before puberty (37) or who are deficient in 5a-reductase-2 (38,39). Early work on risk factors for BPH suggested that men with alcoholic cirrhosis of the liver, which leads to decreased testosterone concentrations and in some cases increased estrogen concentrations (9), were less likely to have BPH nodules at autopsy, although study methods did not always take into account differing age distributions among cases and controls and findings were not entirely consistent between studies (40,41).…”

History of weight and obesity through life and risk of benign prostatic hyperplasia

“…24 Obesity has effects on many hormones, including an increase of estrogen and decrease of testosterone levels, 1 due to aromatization of androgens to estrogens in the adipose tissue. 25 Androgens are involved in the development and maintenance of BPH, as supported by androgen receptor expression in prostate epithelium, 26,27 and by the observation of high testosterone levels in men with prostate cancer in several, although not all studies. 28 Androgen receptor gene polymorphisms (and particularly a CAG repeat length of o21 and a CGN repeat length o16) was also associated with the risk of BPH in a study from Olmsted County, MN, USA.…”

Intranuclear Androgen Receptor Deployment and Protooncogene Expression in Human Diseased Prostate

“…Smaller fragments damaged by TUR were discarded and only those from which charred material could be removed to leave satisfacto rily uninjured samples were used [15]. Homogenization of tissue, preparation of nuclei and exhaustive nucleolysis to yield total pop ulations of nuclease-extractable and nuclease-resistant androgen re ceptors have been described [13,14], Under the conditions em ployed, 'nuclease-resistant' described those receptors which had not been solubilized during a digestion procedure following which no more nuclear material could be released by the action of micrococ cal nuclease (used routinely) or any other nuclease alone. In this report, 'nuclease-extractable' describes those androgen receptors which have been solubilized during such a procedure.…”

“…However, this new emphasis presents fresh complications. Determina tions on high-ionic-strength extracts of nuclei [1][2][3][4][5] ig nore a considerable population of androgen receptors which is resistant to such treatment [2][3][4]8], and which has, by virtue of its association with the nuclear matrix, been proposed as a biologically active component [2], In both cancer and benign prostate hypertrophy (BPH), nuclear androgen receptors may differ quantitatively or in intranuclear deployment from the normal condition [8,[10][11][12], Moreover, the intranuclear deployment of androgen receptors can differ markedly between cancer and BPH samples of similar quantitative receptor con tent [13,14], Anomalies in androgen receptor distribu tion may relate not only to the aetiology of the diseases but also to the disparate development of carcinoma and BPH. This report describes in greater detail the dissimi larities in intranuclear deployment of androgen recep tors in prostate cancer and BPH, and also recounts pre liminary investigations into the relationships of andro gen receptors and the expression of genes which may be implicated in the initiation or progression of cancer.…”