bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association states of androgen receptors in nuclei of human benign hypertrophic prostate
Authors: Kyprianou Natasha , Davies Peter 
Published: February 2007

AbstractAndrogen 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 KCl 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 KCl and nuclease, and variability in total nuclear AR concentration was due to variation in the nonextractable population.
Biochemical nature of the prostate‐associated antigen identified by the monoclonal antibody, KR‐P8
Authors: Raynor Robert H. , Hazra Tapan A. , Moncure Charles W. , Mohanakumar T. 
Published: February 2007

AbstractThe KR‐P8 monoclonal antibody identifies an organ‐specific antigen that is associated with normal as well as malignant specimens of human prostate tissue. The antigen is secreted by cells of the prostate and is present in samples of seminal plasma. Data presented here describe the biochemical nature of the antigen that is recognized by KR‐P8 as it occurs in seminal plasma and in extracts prepared from cells of the prostate tumor line, PC3. Antigen contained in seminal plasma migrated as a broad band on SDS‐polyacrylamide gels in the molecular weight range of 48,000–75,000 d. A similar pattern was observed for antigen prepared from detergent extracts of PC3 cells. The antigen was found to be sensitive to treatment with trypsin and chymotrypsin and the contribution of carbohydrate residues to the structure of the molecule was shown by studies that demonstrated binding of the antigen to Concanavalin A and Soybean Agglutinin lectins. Loss of antigenicity subsequent to periodate oxidation suggested that carbohydrate units are involved in the recognition site for KR‐P8 on the antigen.
Water imbibition in the rat prostate during castration‐induced regression
Authors: Lee Chung , Bahnson Robert R. , Blum Michael D. , Anderson Dean P. , Bockrath John J. 
Published: February 2007

AbstractThe present study was conducted to examine changes in water concentration in the ventral prostate of adult rats at different intervals following castration. The prostatic dry weight was obtained by drying the fresh prostate at 70°C for at least 110 hr and the prostatic water content was calculated from its wet and dry weight. Under normal conditions, the prostatic water concentration ranges from 81.9 to 82.7% in uncastrated rats. The prostatic water concentration started to increase at 8 hr postcastration (83.1%) but this increase was not statistically significant. By 16 hr postcastration, the prostatic water concentration (83.8%) became significantly higher than that of the uncastrated animals. In rats of day 1 to day 10 postcastration, the prostate contained significantly more water (84.4%‐84.7%) than those in uncastrated animals. By day 21 postcastration, the prostatic water concentration (81.5%) was not significantly different from that of uncastrated rats. Unlike the prostate, the skeletal muscle did not significantly change the water concentration following castration. The 51Cr‐EDTA space in the prostate was not significantly different in rats before and after castration. These results indicate that water imbibition in the rat prostate is associated with an active period of prostatic regression and that the change in the 51Cr‐EDTA space during prostatic regression is not the major cause of water imbibition in the tissue. Therefore, the present findings suggest that castration‐induced water imbibition in the rat prostate is caused by an increase in the intracellular water space.
Differential localization and androgen sensitivity of prostatic nuclear protein kinases in euchromatin and heterochromatin fractions
Authors: Norvitch Mary Ellen , Ahmed Khalil 
Published: February 2007

AbstractWe have examined the distribution and androgenic regulation of protein kinases and phosphoproteins in euchromatin and heterochromatin fractions of rat ventral prostate chromatin. Available procedures to prepare euchromatin and heterochromatin fractions were found to result in the loss of various chromatin‐associated protein kinases even though there was no gross change in the gel electrophoretic profile of proteins in these fractions. This loss was prevented by the addition of 0.5 mM phenylmethylsulfonyl fluoride throughout the preparative procedures, which indicates that the protein kinases associated with the chromatin may be particularly susceptible to proteolytic degradation during further subfractionation. By utilizing an improved method for fractionation of chromatin, we have demonstrated a marked enrichment of protein kinase activity (towards phosvitin and endogenous chromosomal proteins) in the euchromatin fraction as compared with heterochromatin. Both of these fractions were also examined for the incorporation of 32P into two main classes of nonhistone proteins (namely, H2SO4‐soluble and ‐insoluble nonhistones). The amount of 32P incorporated into heterochromatin‐associated proteins of both classes was markedly less than that in the euchromatin‐associated proteins. Protein kinase activities (especially those active towards phosvitin and nonhistone proteins) in the euchromatin fraction as compared with the heterochromatin were significantly reduced within 24 h after androgenic deprivation in the animal. The decreased phosphorylation of nonhistone proteins could be attributed to the loss of endogenous protein kinase activity. The results indicate that not only are chromatin‐associated protein phosphokinases preferentially localized in euchromatin fractions but also that these euchromatin‐associated protein kinases display the greatest sensitivity to androgenic status of the animal.
Characterization of androgen receptors in normal and malignant human prostatic tissues
Authors: Radwan Farouk , Léger Francine , Lehoux Jean‐Guy , Carmel Michel , Elhilali Mostafa 
Published: February 2007

AbstractThe aim of this work was to study the physico‐chemical characteristics of androgen receptors of normal and malignant human prostatic tissues. Association (k+1) and dissociation (k−1) rate constants and sedimentation profiles on sucrose density gradients were determined on [3H]androgen receptor complexes. In the presence of 20 mM sodium molybdate, no significant difference in k+1 and k−1 values could be found between cytosolic receptor preparations from normal and malignant specimens. The values obtained for k+1 (mean ± SD) were 5 ± 2 × 106M−1 min−1 (N = 3) and 5 ± 2 × 106M−1 (N = 5); k−1 values of 23 ± 4 × 10−4 min−1 (N = 4) and 25 ± 3 × 10−4 min−1 (N = 5) were obtained for normal and malignant tissues respectively. Similar Nmax values were also obtained for normal [(mean ± SD) 26 ± 10 fmol/mg cytosolic protein (N = 5)] and malignant [20 ± 9 fmol/mg protein (N = 7)] tissues. A statistically significant difference was found however, between k−1 values measured on [3H]androgen receptor complexes of nuclear extracts; values of 15 ± 3 × 10−4 min−1 (N = 4) and 9 ± 1 × 10−4 min−1 (N = 6) were found for normal and malignant tissue preparations respectively. This was also accompanied by a higher level of androgen receptors in nuclear extracts of malignant [Nmax, 308 ± 171 fmol/ g of tissue (N = 8)] compared to normal [Nmax, 68 ± 11 fmol/g of tissue (N = 5)] tissues.The cytosolic [3H]androgen receptor complexes prepared from normal tissues sedimented mainly in the 8–9S area on sucrose density gradient whereas those from malignant tissues sedimented 50% in the 8–9S area and 50% in the 4S area.In conclusion, in this study, we found a different sedimentation profile of androgen‐receptor complexes from the cytosol of prostatic cancers compared to normal as well as a diminution of their dissociation rate constant in nuclei.
Androgenic induction of DNA synthesis in prostatic glands induced in the urothelium of testicular feminized (Tfm/Y) mice
Authors: Sugimura Yoshiki , Cunha Gerald R. , Bigsby Robert M. 
Published: February 2007

AbstractIt has been shown previously that wild‐type urogenital sinus mesenchyme can induce the formation of prostate‐like glandular structures in urinary bladder epithelium derived from adult Tfm (testicular feminization) mice. Total DNA synthesis within these tissue recombinants has been shown biochemically to be androgen sensitive. To determine which tissue (epithelium or stroma) accounts for this androgen‐dependent DNA synthesis, an autoradio‐graphic study was performed with tissue recombinants composed of rat wild‐type urogenital sinus mesenchyme (UGM) associated with bladder epithelium from either wild‐type (BLE) or Tfm mice (Tfm BLE). Both types of recombinants were grown under the kidney capsule of male athymic nude mice for 4 weeks. The hosts were then castrated, and 2 weeks later were treated with either testosterone propionate (TP), TP plus cyproterone acetate (CA), or oil vehicle for 3 days. DNA synthetic activity was measured through analysis of labelling index (LI) after incorporation of 3[H]‐thymidine in vivo. For both UGM + BLE and UGM + Tfm BLE recombinants thymidine incorporation in epithelial cells greatly exceeded that of the stromal cells. TP stimulated epithelial LI to a similar degree (about 50‐ to 200–fold greater than controls) in both UGM + BLE and UGM + Tfm BLE recombinants; CA antagonized the effect of TP. Nuclear 3H‐DHT binding was observed autoradiographically within the epithelial cells of the induced epithelium of UGM + wild‐type BLE recombinants, but not within epithelium of UGM + Tfm BLE recombinants. Wild‐type mesenchymal cells in both tissue recombinants showed specific nuclear 3H‐DHT uptake. Thus, the proliferative effect of androgens upon prostatic epithelium is not a direct effect mediated by intra‐epithelial androgen receptors, but rather it appears to be elicited indirectly via regulatory influences from androgen‐receptor‐positive stromal cells.
Androgen‐dependent growth regulation of and release of specific protein(s) by the androgen receptor containing human prostate tumor cell line LNCaP
Authors: Berns Els M. J. J. , De Boer Willem , Mulder Eppo 
Published: February 2007

AbstractHormone sensitivity, as indicated by the presence of steroid hormone receptors and by the effect of androgens and anti‐androgens on the release of proteins by cultured cells of the human prostate tumor cell line lymph node carcinoma of the prostate‐fast growing colony (LNCaP‐FGC), has been studied.The growth of the LNCaP‐FGC cells were stimulated by androgens in a dose‐dependent way. Under optimal conditions the synthetic nonmetabolizable androgen 17β‐hydroxy‐17α‐methyl‐(3H)‐estra‐4,9,11‐trien‐3‐one (R1881) (0.1 nM) stimulated cell growth by approximately 2.3 times. Increasing doses of R1881 (1–100 nM) partly decreased the stimulation of the cell growth. The anti‐androgen cyproterone acetate exerted inhibitory effects on cell growth. The nuclear extract of the LNCaP‐FGC cells contained 17,000 ± 2,500 (mean ± SD) KCl‐extractable, nuclear androgen receptor sites/cell. Estrogen and progesterone receptors were not detectable in the nuclear extracts nor in cytosol, indicating that these receptors were absent.The release of proteins in the culture medium was studied using incorporation of the 35S‐methionine, sodium dodecyl sulfate (SDS)‐gel electrophoresis, and fluorography. Cells grown in media containing charcoal‐stripped fetal calf serum released significantly lower amounts of a protein with an apparent molecular mass of 42,000 daltons. The release of this 42‐kD protein could be restored in cells cultured in the presence of 5α‐dihydrotestosterone (0.1–1 μM) or R1881 (0.1–100 nM), whereas the addition of estrogens or corticosteroids had no effect. In the presence of anti‐androgens, such as cyproterone acetate and 5,5‐dimethyl‐3‐(4‐nitro‐3‐(trifluoro‐methyl)‐phenyl)‐2,4‐imidasolidinedione, inhibitory effects on the release of the 42‐kD protein were observed. The observed parallel between the effects of (anti)‐androgens on the growth of the LNCaP prostate cells and the release of the 42‐kD protein suggests that this protein is involved in the regulation of malignant prostate cell growth.
Establishment and characterization of seven dunning rat prostatic cancer cell lines and their use in developing methods for predicting metastatic abilities of prostatic cancers
Authors: Isaacs John T. , Isaacs William B. , Feitz Wouter F. J. , Scheres Jack 
Published: February 2007

AbstractIn vitro cell lines were established from seven biologically distinct in vivo Dunning R3327 rat prostatic tumor sublines. Some of these in vitro cell lines (i.e., G, AT‐1, AT‐2) retain a low metastatic ability when inoculated back into syngeneic Copenhagen male rats, while others (i.e., AT‐3, MAT‐LyLu, MAT‐Lu) retain a very high metastatic ability. A series of genetic (i.e., DNA content per cell, modal chromosomal number), as well as phenotypic parameters (i.e., morphology, 5α‐reductase, androgen receptor, estrogen receptor) were used to validate that the in vitro cell lines retained the major characteristics of the parental in vivo tumor sublines used for their respective establishment.A series of additional characteristics (i.e., morphology, growth rate, saturation density in surface culture, anchorage‐dependent and ‐independent clonogenic potential) were compared between the high vs. the low metastatic in vitro cell lines to determine if a discriminatory parameter could be identified which reproducibly predicted the metastatic abilities of the particular prostatic cancer cell line. While the combination of the in vitro cell lines and their parental in vivo tumor subline will be a valuable tool for developing methods for predicting metastatic ability of prostate cancers, no single parameter yet measured is entirely successful in making this important distinction.
Effect of age, castration, and testosterone replacement on the development and restoration of canine benign prostatic hyperplasia
Authors: Berry Stephen J. , Ewing Larry L. , Coffey Donald S. , Strandberg John D. 
Published: February 2007

AbstractAn experiment was designed to test the effect of castration and testosterone replacement on the development of benign prostatic hyperplasia (BPH) in young and on the restoration of BPH in old beagles. Twenty beagles were divided by age into young (1.5–2.5–yr) and old (6.0–8.5‐yr) groups. Each of these groups was further divided randomly into two additional groups of age‐matched, intact, untreated control and castrate beagles. The latter were then treated with testosterone‐filled Silastic implants designed to clamp serum testosterone at concentrations similar to those observed in adult beagles for 7 months beginning 5 months after castration. Histopathologic characterization of each prostate was completed on biopsy material obtained at the beginning and end of the experiment. Prostate weights were determined each month for 12 months via a noninvasive two‐dimensional X‐ray procedure [1]. Testosterone treatment for 7 months allowed BPH to develop in young and restored BPH in old beagles. These results suggest that testosterone in the adult beagle acts permissively to allow BPH to develop in the prostrate of the aging dog. Some other testicular product may be required for the continued growth of BPH in aged beagles.
Estrogen formation in human prostatic tissue from patients with and without benign prostatic hyperplasia
Authors: Stone Nelson N. , Fair William R. , Fishman Jack 
Published: February 2007

AbstractProstatic tissue removed at the time of cystoprostatectomy was separated into periurethral and peripheral zones. Homogenized tissue was incubated with [1,2,6,73H] androstenedione in the presence or absence of an aromatase inhibitor, 4‐hydroxyandrostenedione (4‐OHAD) and a 5α‐reductase inhibitor 4‐MA (N,N‐diethyl‐4‐methyl‐3‐oxo‐4‐aza‐5α‐androstane 17β‐carboxamide). Estrogen formation was determined by reverse isotope dilution of [3H] estrone and [3H] estradiol and crystallization to constant specific activity. Control incubations were carried out in parallel utilizing heated prostatic tissue. Total estrogens produced in the periurethral zone in patients with benign prostatic hyperplasia (BPH) was 223 fmol/ mg protein/hr (SE ± 57) compared to 102 fmol (SE ± 17) in patients without BPH. Estrogen formation in the peripheral zone was 175 fmol (SE ± 69) and 105 fmol (SE ± 26) in patients with and without BPH, respectively. The prostatic aromatase exhibits Michaelis‐Menton kinetics with an apparent Km of 90 nM. 4‐OHAD inhibited aromatization in the prostatic tissue by 57‐93%. Aromatization was also strongly inhibited by 4‐MA, indicating that 4‐MA is a potent aromatase as well as a 5α‐reductase inhibitor in this tissue. These results suggest that aromatization of androgens to estrogens in the human prostate proceeds at a substantial rate and that local estrogen formation could preexist and be a factor in the etiology of BPH and prostatic cancer.
Development of canine benign prostatic hyperplasia with age
Authors: Berry Stephen J. , Strandberg John D. , Coffey Donald S. , Saunders William J. 
Published: February 2007

AbstractThe prevalence and growth of benign prostatic hyperplasia (BPH) in beagles as a function of age were studied. The normal prostate gland was 12 ± 3 gm in beagles 2.1‐3.0 years of age; this weight remained unchanged unless BPH developed. Histologic evidence of BPH developed at an early age with a prevalence of 16% of the dogs by the age 2 years. Fifty percent of the dogs had BPH, determined histopathologically by age 4.1‐5.0 years. The average weight of the prostate gland remained constant until after age 8 years. With age, the pathologic features of BPH changed from glandular to the complex form, with no increase in prostate weight until after 8 years. Reinitiation of growth occurred and prostate weight increased to greater than 36 gm in eight of 185 beagles older than age 8 years.
Role of epithelial‐stromal interactions in the control of gene expression in the prostate: An hypothesis
Authors: Tenniswood Martin 
Published: February 2007

AbstractAn hypothesis that explains the effects of stromal‐epithelial interactions on the mechanism of action of androgens is presented. This hypothesis proposes the existence of three factors, two growth factors referred to as “stromally derived growth factor” (SDGF) and “epithe‐lially derived growth factor” (EDGF), and one inhibiting factor, “epithelially derived inhibiting factor” (EDIF), which together modulate the replicative and transcriptional processes of the prostate. The hypothesis attempts to explain the well documented modulation of epithelial morphology and function by the stromal cells of the prostate that occurs during development. It also describes the role of each of the factors in the mature prostate, and suggests that in the adult the interaction between the stroma and epithelium, while still significant does not greatly influence the action of androgens, which exert their effects via the classical steroid receptor mechanism.
Nuclear protein matrix as a target for estramustine‐induced cell death
Authors: Hartley‐Asp Beryl , Kruse Elisabeth 
Published: February 2007

AbstractThe effect of estramustine [estradiol 3–N‐bis(2–chloroethyl)carbamate] on the human prostatic tumor cell line 1013L was investigated. Cell proliferation experiments revealed that estramustine cytotoxicity varied during the different phases of cell growth. Maximum cell killing was found in early log phase, but cell death also occured in the stationary phase. Mitotic arrest was found at cytotoxic concentrations throughout the log phase. Subcellular distribution studies showed that the cellular uptake of estramustine increased throughout the log phase and remained steady during the stationary phase. Nuclear uptake in contrast was similar in all phases, whereas a preferential binding to the nuclear protein matrix was found to increase throughout the log phase and even during the stationary phase of growth. This implicates the nuclear protein matrix as a target for estramustine cytotoxicity.
Echogenic structure of prostatic cancer imaged on radical prostatectomy specimens
Authors: Salo J. O. , Rannikko S. , Mäkinen J. , Lehtonen T. 
Published: February 2007

AbstractTwenty radical prostatectomy specimens were scanned ultrasonically in vitro using a transrectal ultrasonic probe to evaluate the ultrasonic pattern of prostatic cancer. Histological and ultrasonic findings of the same areas were compared. No ultrasonic pattern specific for intracapsular prostatic cancer was found. Most often (in 40% of cases) the areas of prostatic cancer appeared hypoechoic on the ultrasonograms. In 30% of cases the carcinoma had a hyperechoic or mixed ultrasonic pattern, and in 30% the echo structure of the prostate was fairly uniform; intracapsular cancer could not be detected ultrasonically in these latter cases. The lack of a specific ultrasonic pattern for intracapsular prostatic carcinoma reduces the value of transrectal ultrasonography in detecting early intracapsular cancers. The main value of ultrasonography in patients with prostatic cancer is in the preoperative staging of the disease and in the follow‐up of patients.
DNA synthesis in the canine prostate: Effects of androgen and estrogen treatment
Authors: Barrack Evelyn R. , Berry Stephen J. 
Published: February 2007

AbstractCanine prostatic DNA synthesis was evaluated by measuring [3H]thymidine incorporation into DNA of tissue slices in vitro. Among untreated beagles, prostatic DNA synthesis rates in young dogs with normal prostates, young dogs with spontaneous benign prostatic hyperplasia (BPH), and old dogs with BPH were 676 ± 186, 1,220 ± 156, and 641 ± 88 cpm/100 μg DNA/hr, respectively. Among 81 young beagles (intact or castrated) that had been treated for 4 months with various steroids, rates of DNA synthesis varied according to the type of hormonal treatment. Prostatic DNA synthesis (cpm/100 μg DNA/hr) was significantly different (P < 0.001) for dogs treated with estradiol alone (1,658 ± 221 cpm/100 μg DNA/hr; n = 10 dogs), androgen alone (testosterone, 5a‐dihydrotestosterone, or 5a‐androstane‐3a, 17β‐diol; 1,000 ± 61 cpm/100 μg DNA/hr; n = 40 dogs), or a combination of androgen plus estradiol (591 ± 49 cpm/100 μg DNA/hr; n = 31 dogs). However, there was no correlation between prostate size and rate of DNA synthesis (cpm/100 μg DNA/hr). Although treatment with estrogen alone resulted in the highest rate of DNA synthesis, it produced squamous metaplasia and the smallest prostates; these results are indicative of a high rate of cell turnover. Comparing prostates that reached the same size following 4 months of treatment with androgen alone or androgen plus estrogen, the rate of prostatic cell turnover was lower in the androgen plus estrogen group. These results are interpreted to indicate an inhibitory effect of estradiol on the rate of cell death in the presence of androgens.