bluuebunny/crossref_metadata_2025 huggingface dataset:
Hormonal effects on zinc concentration and morphology of rat lateral prostate gland
Authors: Itaya Patricia W. , Thompson Sue Ann , Heidger Paul M.
Published: February 2007

Hypophysectomized rats were injected with prolactin and/or testosterone, and luteinizing hormone (LH) and prolactin and/or follicle‐stimulating hormone (FSH). Tissue from the lateral prostate was processed for spectrophotometric determination of zinc and for electron microscopy. Changes in zinc concentration, epithelial height, and morphological characteristics were used to assess the effect of hormonal replacement on functional activity. Although testosterone administration resulted in full restoration of all parameters, there was no evidence of a synergistic effect of prolactin and testosterone. Prolactin alone decreased the zinc concentration and increased the epithelial height compared with control animals, and there was evidence of epithelial hyperplasia. Luteinizing hormone, alone or combined with prolactin or prolactin and FSH, resulted in a marked increase of epithelial height and restoration of morphological features found in intact animals; however, only a slight increase of zinc concentration over control values was elicited. Combined LH and FSH administration reduced epithelial height and zinc concentration compared with the other LH regimes, and there was evidence of cellular degeneration.
The prostate of the gorilla
Authors: Jacobs Stephen C. , Beehler Bruce A. , Boese Gilbert , Story Michael T. , Clowry Lawrence J. , Lawson Russell K.
Published: February 2007

The prostate gland from a 32‐year‐old gorilla was examined. The prostate weighed 15 g and was composed primarily of dilated cystic acinar areas with only modest stromal thickening. The acini were lined by a low cuboidal epithelium. A second minor population of smaller glands with extensive papillary projections was also present. The epithelial cells stained densely for acid phosphatase and prostatic‐specific antigen. Human prostatic acid phosphatase content of the gland as determined by radioimmunoassay was 2.3 mg/g protein. This is the first published histologic description of a gorilla prostate. The animal was in late middle age but did not display predominant prostatic stromal hyperplasia. Prostatic acid phosphatase from the gorilla cross‐reacts immunologically, or is identical to human prostatic acid phosphatase.
Thyrotropin‐releasing hormone (TRH) activates the adenylyl cyclase of nonsecretory cells in the rat ventral prostate
Authors: Purvis Kenneth , Brekke Inger , Attramadal Arne , Gordeladze Jan O.
Published: February 2007

Prostatic secretory and basal or stem cells were isolated from rat ventral prostate lobes by collagenase dispersion and density centrifugation in a Percoll gradient. The membrane‐bound adenylyl cyclase of secretory cells could be activated in a dose‐dependent manner by vasoactive intestinal peptide (VIP ED50 10−7M) but not thyrotropin‐releasing hormone (TRH). Conversely, only TRH could significantly stimulate the adenylyl cyclase in basal cell membranes (ED50 5 × 10−7). In two separate studies enzyme activity was stimulated seven‐ and 13‐fold by this peptide. This action of TRH on prostatic basal cells supports previous reports that high levels of immunologically active TRH have been found in prostate tissue and that TRH stimulates the growth of prostatic cancer cells in vitro.
Characteristics of the inhibitory effect of chronic treatment with an LHRH agonist on testicular steroidogenesis in the dog
Authors: Tremblay Yves , Bélanger Alain , Labrie Fernand , Frenette Gilles , Dubé Jean Y. , Tremblay Roland R.
Published: February 2007

Daily subcutaneous administration for 3 months of the potent LHRH agonist (D‐Ser(TBU)6, des‐Gly‐NH210) LHRH ethylamide (25 μg) to adult dogs having spontaneous benign prostate hyperplasia (BPH) causes a marked inhibition of testicular androstenedione and testosterone secretion. This inhibition of Δ4‐androgen secretion is accompanied by a decrease of testicular progestin precursors and 5α‐androgen metabolites, thus suggesting that, in dog, the loss of testicular steroidogenic activity, induced by the administration of an LHRH agonist, is due to a total inhibition of testicular steroidogenesis. In plasma, the concentration of both testosterone and dihydrotestosterone is also markedly depressed while androstane‐3α, 17β‐diol levels remain unchanged. Measurement of prostatic steroid content has shown that administration of the LHRH agonist as well as castration is associated with a marked decrease in androstenedione, testosterone, and dihydrotestosterone levels in prostate while there is a small inhibition of androst‐5‐ene‐3β,17β‐diol, androstane‐3β,17β‐diol, dehydroepiandrosterone, and estrone concentrations in this tissue. The present data show that treatment with an LHRH agonist in the dog causes a marked inhibition of testicular steroid secretion similar to the one observed in adult men, and suggest that steroids from adrenal origin may also be involved in prostatic function.
Grading of prostatic cancer (I): An analysis of the prognostic significance of single characteristics
Authors: Schroeder Fritz H. , Blom Jan H. M. , Hop Wim C. J. , Mostofi F. K.
Published: February 2007

This paper contains the first part of an attempt to quantitate the impact on prognosis of various parameters used in grading of prostatic cancer. Out of 346 patients of Elmer Belts series, 113 were identified whose tumors showed homogeneity with respect to single characteristics of a total of 12 parameters applied for grading in Mostofi's system. By this procedure it was possible to eliminate the possible influence on prognosis of the presence of several tumor formations within the same tumor. By using overall and intercurrent death corrected survival as end points, the impact of each of the 12 parameters on prognosis was studied. Only the architecture of the tumor (the parameter “glands”), variation in size and shape of the nucleus (anaplasia), and grade significantly influenced overall survival. In addition, corrected survival was significantly dependent on the amount of tumor seen and on the presence of mitoses.

Subsequently, an attempt was made to replace “grade” by single parameters which had been shown previously to be of prognostic significance. It turned out that this was not possible. Grade is largely dependent on architecture and nuclear pleomorphism, but neither one of these parameters alone can reproduce “grade.” Multivariate analysis was next used to further determine the prognostic weight of the individual parameter, and, if possible, to construct a new, more efficient grading system. These results will be reported separately [8]. It is unknown at the present time what the impact of several architectural formations within the same tumor on prognosis may be. The number of different formations found ranges from 1 to 4 in this material; 668 different formations belonging to 346 tumors were graded. The results of this analysis will be reported in part two of this series of papers [7].
The effect of prolactin on human BPH epithelial cell proliferation
Authors: Syms A. J. , Harper M. E. , Griffiths K.
Published: February 2007

Epithelial cell monolayers derived from specimens of human benign prostatic hyperplasia (BPH) tissue by an explant culture technique were cultured with prolactin in the presence and absence of androgens. Proliferation of the cells was measured by both autoradiographic assessment of [3H]‐thymidine uptake and stathmokinetic procedures. Prolactin significantly stimulated the growth of these cells in the concentration range 0.5 mIU/ml to 10 mIU/ml but was inhibitory at a concentration of 100 mIU/ml. In the presence of testosterone (1 × 10−7 M), prolactin at low concentrations (> 1 mIU/ml) but not at 10 mIU/ml, the concentration at which all other experiments were performed, produced a further stimulation in the proliferation. The increase in growth seen with cells cultured with 5α‐dihydrotestosterone (1 × 10−7 M) was reduced with addition of prolactin at high concentrations (10–100 mlU). When the fetal calf serum used in the cultures was stripped of endogenous steroids, prolactin still increased cell proliferation, although to a reduced extent. This indicated that the effects of prolactin were not dependent on the presence of androgens.
Binding characteristics of inhibin in rat ventral prostate
Authors: Vanage G. R. , Phadke M. A. , Sheth A. R.
Published: February 2007

Homogeneous preparation of human seminal plasma inhibin (molecular weight 13,500) was iodinated with 125I to a specific activity of about 40–45 μCi/μg and tested for binding to a rat prostate crude membrane preparation. The binding of inhibin was a saturable process as well as time and temperature dependent. This binding was displaceable in a dose‐dependent manner by unlabelled inhibin. Other hormones such as LH, FSH, Prl, and TSH from rat or human origin did not influence the binding of labelled inhibin to rat prostate membrane. Of various age groups of rats studied, the maximum binding was observed in 75‐day‐old rats. The radiolabelled inhibin also showed specific binding to rat pituitary. The preliminary studies regarding involvement of steroids in the control of inhibin receptors in prostate and pituitary indicated that testosterone activates the inhibin receptors at the prostatic level whereas estradiol did not have any effect. However, estradiol increases the pituitary receptors for inhibin as compared to testosterone.
Antiprostate carcinoma monoclonal antibody (D83.21) cross reacts with a membrane antigen expressed on cytomegalovirus‐transformed human fibroblasts
Authors: Campbell Ann E. , Beckett Mary L. , Starling James J. , Sieg Susan M. , Wright George L.
Published: February 2007

Virological and epidemiological studies have implicated human cytomegalovirus (HCMV) as a possible etiological agent of prostate cancer. Because of the suspected associations, this laboratory tested the reactivity of a prostate‐associated monoclonal antibody with HCMV‐transformed cells. This mouse monoclonal antibody, D83.21, reacts with a membrane antigen on prostate and bladder tumor cells and does not bind to a variety of other malignant or normal cells. The results of this study indicated that the prostate‐associated antibody bound to a membrane antigen on HCMV‐transformed cells as detected by radioimmunoassay, immunofluorescence, and complemented‐dependent cytotoxicity. This cross‐reactivity appeared to be specific for HCMV‐transformed cells and did not react with HCMV‐infected cells or those transformed by other viruses. Antibody affinity chromatography, used to isolate the D83.21‐reactive protein, revealed two peptides of 60 and 28 kd on both prostate tumor and HCMV‐transformed cells. The results suggest that D83.21 reacts with a common cell surface protein expressed on HCMV‐transformed cells and urogenital tumors.
Dimethylsulfoxide‐induced changes in a rat prostate adenocarcinoma
Authors: Wenger Allen S. , Hall Margot , Mickey George H. , Silverman Lawrence , Fried Floyd A. , Mickey Don D.
Published: February 2007

A variety of agents can induce mammalian tumor cell lines to acquire characteristics of the normal cell counterpart. Dimethylsulfoxide (DMSO) has been an effective differentiating agent in many tumor cell lines. In the present study a Dunning rat prostate tumor subline, MAT LyLu, available as an in vitro continuous cell culture was treated with 2.25% DMSO (vol/vol).

Treated MAT LyLu cells had a decreased growth rate, saturation density, and clonogenicity, an increased doubling time, and alterations in enzyme activity and tumorigenicity when compared to untreated MAT LyLu cells. The cell viability of treated cells at the saturation density was greater than 90%.

MAT LyLu cells treated with DMSO and then removed from DMSO (posttreated) when compared to untreated cells had similar growth rates, doubling times, clonogenicities, enzyme activities, and tumorigenicities. Posttreated MAT LyLu cells had a different growth pattern than untreated MAT LyLu cells. Posttreated cell viability at saturation density was greater than 90%.

This investigation demonstrated that a rat prostate adenocarcinoma grown in medium containing 2.25% DMSO acquired characteristics consistent with differentiated prostate cells. Posttreated MAT LyLu cells were similar in many characteristics to untreated cells but were not identical. The alterations noted were not cytotoxic and were not completely reversible. The results of this study correlated with the observations of other investigators who have studied mammalian tumor cell lines exposed to DMSO.
Effect of estrogen and androgen administration on α‐difluoro‐methylornithine‐enhanced putrescine uptake by the rat prostate
Authors: Kadmon D. , Mahle C. , Heston W. D. W. , Hahn D. A.
Published: February 2007

Radiolabeled putrescine is a potential imaging agent for carcinoma of the prostate. The intrinsically high uptake of putrescine into the rat prostate and prostatic carcinoma can be further stimulated by pretreatment of the animals with α‐difluoromethylornithine (DFMO) uptake, a polyamine synthesis inhibitor. Pharmacological castration of the animals followed by androgen stimulation and DFMO pretreatment achieved a 30:1 prostate/muscle ratio of 14C‐putrescine uptake in elderly rats.
Prostate cancer in a Sprague‐Dawley rat
Authors: Pollard Morris , Luckert Phyllis H.
Published: February 2007

An adenocarcinoma of the prostate gland developed in one rat of the Lobund Sprague‐Dawley (S‐D) strain, following treatments with testosterone propionate in silastic membranes. The transplanted cells (PA‐SD1) developed local tumors, metastasized through lymphatic channels to the lungs, and induced osteolytic lesions when deposited adjacent to the calvarium. In vitro‐propagated PA‐SD1 cells produced the same tumor type in Lobund strain S‐D rats as that from which it was derived.
Grading of prostatic cancer: II. The prognostic significance of the presence of multiple architectural patterns
Authors: Schroeder Fritz H. , Blom Jan H. M. , Hop Wim C. J. , Mostofi F. K.
Published: February 2007

This second report in a series of three deals with the prognostic importance of the presence of multiple, histologically identifiable architectural patterns in prostatic carcinomas. In the previous paper three of 12 parameters studied were identified as being prognostically significant in patients with single architectural patterns (formations) present in their tumors. The three parameters are nuclear anaplasia, architecture (“glands”), and mitoses, if present. The questions of whether “the worst part of a tumor determines prognosis” or “the presence of differentiated formations improves prognosis” are investigated by applying these parameters to patients with multiple tumor formations. Overall and corrected survival served as parameters.

It was shown that the parameters shown to be of importance for prognosis in tumors with single formations also have significant influence in patients with multiple formations. The worst formation determines prognosis, but patients with poorly differentiated tumors do significantly worse if their tumor is homogeneous. The presence of better‐differentiated formations improves the prognosis of the worst formation. The observations made are discussed in view of the histopathogenesis of prostatic cancer.
Effects of long‐term administration of tamoxifen on steroid metabolism in prostatic carcinoma patients
Authors: Bolton Nicholas J. , Vihko Pirkko , Leinonen Pekka , Kontturi Matti , Vihko Reijo
Published: February 2007

Six patients with advanced prostatic carcinoma were treated with tamoxifen (2 × 20 mg daily) for up to 3 months before orchiectomy. Blood samples for gonadotropin, sex steroid, and prostate‐specific acid phosphatase (PAP) determinations were taken before tamoxifen treatment, daily for 1 week, and at monthly intervals. Steroid concentrations in the testis tissue and spermatic vein blood were assayed from samples taken at orchiectomy. No consistent changes were observed during tamoxifen treatment, although there was a transient drop in the mean concentrations of LH on days 3 and 4 of treatment. The circulating concentrations of estradiol tended to be increased at 1, 2, and 3 months of treatment. The spermatic vein concentrations of testosterone and its precursors tended to be higher than those in nontreated prostatic carcinoma patients previously reported from this laboratory, indicating slight stimulation of testicular steroidogenesis. There were no changes in circulating levels of PAP and no improvement in clinical condition, indicating that long‐term tamoxifen administration is not effective in the treatment of prostate carcinoma.
On the role of aging in cancer incidence: An interpretation of the prostate cancer anomaly with implications for routine screening
Authors: Cohen Patricia , Dix Douglas
Published: February 2007

Cross‐sectional age‐incidence patterns for the common male and female cancers in Connecticut were normalized to describe the percentage of total incidence that occurred at each age. The pattern for prostate cancer was atypical—less than the 99% confidence limit from the mean at ages less than 60 and greater than the 99% confidence limit from the mean at ages greater than 75. The available international data on latent carcinoma of the prostate, when normalized as above, resembled the mean male and female cancer patterns in Connecticut and suggested that the atypical behavior of clinical prostate cancer was the result of a lag between the incidence of latent carcinoma and promotion to clinical disease. Confirmation of this suggestion, with the potential to distinguish epidemiologically those latent carcinomas that remain asymptomatic from those that progress to malignancy, awaits routine screening for the latent carcinoma.
Grading of prostatic cancer: III. Multivariate analysis of prognostic parameters
Authors: Schroeder Fritz H. , Blom Jan H. M. , Hop Wim C. J. , Mostofi F. K.
Published: February 2007

This work is based on the two previous publications which are concerned with grading prostatic carcinoma. In the present communication the technique of multivariate analysis is applied to quantify the prognostic importance of parameters which were earlier identified as contributing in a significant manner to grading. The results of this analysis are used to construct a scoring system which differentiates five significantly different prognostic groups. When compared to the results of grading, the new system is shown to be superior. The large group of 228 patients with G2 tumors can be split into three groups, each with a significantly different prognosis.

The correlation of the scoring system to local tumor extension (pT category) is described.

Recommendations for grading of prostatic carcinoma resulting from this work are the following: 1) Only three independent parameters are of significance for grading prostatic cancer: tumor architecture, nuclear anaplasia, and the presence or absence of mitoses. 2) The combination of these parameters in a scoring system identifies five separate prognostically different groups. 3) The separation achieved by this new system is superior to conventional grading and is suggested for grading prostatic cancer.
Treatment of advanced prostatic carcinoma with D‐trp‐6‐LH‐RH
Authors: Gonzalez‐Barcena David , Perez‐Sanchez Patricia , Ureta‐Sanchez Sergio , Dominguez Hector Berea , Graef‐Sanchez Alicia , Morales Margarita Becerril , Comaru‐Schally Ana Maria , Schally Andrew V.
Published: February 2007

Twenty patients with stage D2 prostatic carcinoma were treated for up to 18 months with D‐Trp‐6‐LH‐RH. Results of more than 3 months of treatment on these 20 patients are reported. The analog was given SC once daily at a dose of 1,000 μg/day. All patients had bone pain and high levels of acid and alkaline phosphatase. After the first week of D‐Trp‐6‐LH‐RH administration, major decreases in bone pain and reversal of the signs of prostatism were observed. Acid phosphatase gradually fell, achieving normal values after 12 weeks. Initial plasma testosterone was within normal limits, but during treatment with D‐Trp‐6‐LH‐RH it fell to castration levels. Resting values of PRL, GH, TSH, and cortisol did not show significant changes. After TRH, TSH increased in five patients, but five did not respond. However, at 2 and 4 months, all patients released TSH in response to TRH. Two patients died during the treatment with D‐Trp‐6‐LH‐RH despite initial subjective responses and decreases in testosterone levels. The rise in acid phosphatase levels in these two patients was accompanied by a general deterioration, suggesting that they had androgen‐independent cancer. One patient who developed progressive hepatic, bone, and pulmonary metastases in spite of previous orchiectomy was also treated with the analog. Three months later his acid phosphatase levels were within normal values, and partial regression of metastases was observed. These results demonstrate that D‐Trp‐6‐LH‐RH and other LH‐RH agonists can be used as an effective endocrine therapy for advanced prostate carcinoma, thereby avoiding the side effects of estrogens or the psychological impact of surgical castration.
Differences in nonhistone protein changes in rat ventral and dorsolateral prostate during sexual maturation
Authors: Nishi Nozomu , Matuo Yuhsi , Tanaka Yukio , Muguruma Yasuyoshi , Wada Fumio
Published: February 2007

Age‐related changes of chromosomal proteins in the dorsolateral and ventral prostates of rats from 6 to 31 weeks of age were studied by SDS‐polyacrylamide gel electrophoresis. A nonhistone protein having a molecular weight of about 20,000 (20K‐NHP), abundantly localized in the dorsolateral prostate, increased rapidly in content during the early stage of sexual maturation (6‐11 weeks of age) in association with increases of serum testosterone concentration and prostatic tissue weight. Serum testosterone concentration decreased after week 11 and then remained constant until week 31. In contrast, the 20K‐NHP content continued to increase after 11 weeks of age in the dorsolateral prostate, but not in the ventral prostate. The rapid increase of 20K‐NHP in the dorsolateral prostate during the early stage of sexual maturation could not be attained in immature rats (5 weeks of age) by injection of excess amounts of androgens and/or prolactin for a week. But the 20K‐NHP content in the ventral prostate of rats treated with testosterone propionate was almost the same as that of mature rats.
Comparison of subcellular proteins of normal prostate, benign prostatic hypertrophy, and prostatic cancer: Presence of BPH‐associated nonhistone proteins
Authors: Wada Fumio , Nishi Nozomu , Tanaka Yukio , Muguruma Yasuyoshi , Tanaka Koichiro , Matuo Yuhsi , Usami Michiyuki , Kotake Toshihiko , Matsui Sei‐Ichi , Sandberg Avery A.
Published: February 2007

Proteins in the cytosol, postnuclear particulate, and nuclear fractions from seven specimens of normal prostate from bladder cancer patients, 14 specimens of benign hypertrophic prostate (BPH), and three specimens of cancerous prostate were analyzed and compared by SDS‐polyacrylamide slab gel electrophoresis. Abundant protein species in the cytosol fractions were 60K (species having a molecular weight of about 60,000) and 42K; their relative contents were about 35% for 60K and about 12% for 42K. In the postnuclear particulate fraction, 42K was the most abundant (about 10% of the total). The contents of these major protein species were similar in specimens of normal and diseased prostates. In addition, there are marked similarities in the electrophoretic patterns for all the protein (24–29 species) in the cytosol and postnuclear particulate fractions of the human prostate, except for four minor species in the cytosol fraction. Of the nuclear proteins, the content of core histones (H2A, H2B, H3, and H4) was fundamentally similar among all the specimens, whereas the content of H1 histone was different from one specimen to another. The most remarkable and significant difference was that the 42K‐NHP (nonhistone protein having a molecular weight of about 42,000), 55K‐NHP, and 190K‐NHP concentrations were significantly higher in BPH than in normal and cancerous prostates.
A prognostic index for the clinical management of patients with advanced prostatic cancer: A british prostate study group investigation
Authors: Wilson D. W. , Harper M. E. , Richards G. , Pierrepoint C. G. , Griffiths K. , Jensen H. M. , Ikeda R. M. , Peeling W. B.
Published: February 2007

Patients with histologically proven carcinoma of the prostate (n = 186) were initially assessed and followed up according to the standardized protocol of the British Prostate Study Group, urologists from which contributed patients to this investigation. These patients were given either endocrine therapy or orchidectomy as first line treatment; the ratio of the number of patients receiving these two treatment was similar in each group of subjects compared for survival. Prognostic indices were derived for all patients and for those classified according to the presence (M1) or absence (M0) of metastases. The prognostic indices were derived from clinical and hormone data obtained at initial presentation. Whereas the degree of tumor differentiation and plasma testosterone concentrations were significant prognostic factors in both M0 and M1 disease, growth hormone was only significant in M1 patients, where age was also of borderline significance; elevated growth hormone, higher Gleason grade, younger age, and lower testosterone indicated a poorer prognosis in M1 patients. These findings indicated the feasibility of selecting a poor prognostic group of patients that may derive benefit from a more aggressive therapy.
The effect of low‐dose cyclophosphamide and immunologic exposure upon growth of established dunning R‐3327‐G subline rat prostate adenocarcinomas
Authors: Rubenstein Marvin , Shaw Michael W. , McKiel Charles F. , Guinan Patrick D. , Bhatti Rashid A. , Habibi Hossein
Published: February 2007

Utilizing the Dunning rat prostate adenocarcinoma, a low dose of cyclophosphamide (CY), 30 mg/kg, administered either alone or following diethylstilbestrol (DES) therapy, was as effective as higher levels of CY (100 mg/kg) in ability to initiate tumor regression. A lower dose (10 mg/kg) of CY was initially ineffective. Animals which had been injected with tumor an additional 10 days prior to initiation of CY treatment were apparently more responsive to this mode of chemotherapy. The effect of this additional 10 days of immunologic exposure supports the belief that the activity of CY is augmented by the presence of immunologic competence. All animals which responded favorably toward therapy utilizing CY, alone or in combination with DES, were similarly able to reject subsequent tumor challenges. It is thought that low‐dose CY may reduce the immunosuppressive effects observed with higher levels and presumably preserve the helper T cell population necessary to mount secondary immune responses.
Influence of surgical techniques on receptor levels and 5α‐reductase activity of the human prostate gland
Authors: Habib Fouad K. , Smith Trevor , Robinson Rosemary , Chisholm Geoffrey D.
Published: February 2007

This study examines the effects of removing prostate specimens by different surgical techniques on the androgen receptor levels and 5α‐reductase activity of the tissue. Comparison of specimen obtained by transurethral resection (TUR) with those from an open operation revealed that the size of the resected chips was critical in maintaining the hormonal activities of the specimens. Provided that the size (length x thickness) of the resected chips was greater than 1.5 × 0.4 cm there was no effect on either the androgen receptor levels or the testosterone‐metabolizing activity of the tissue, and TUR specimens can therefore be reliably used to assess the hormonal activity of the gland.
Characterization of rat ventral prostatic epithelial cells in collagen gel culture
Authors: O'connor Terence , Sinha Dilip K.
Published: February 2007

The characterization of rat ventral prostatic epithelial cells grown in collagen gel culture was undertaken to determine the usefulness of this culture technique for the study of prostatic growth and differentiation in vitro. The results of these studies demonstrate that embedding prostatic epithelial cells in a matrix of collagen gel permitted rapid proliferation and maintenance of the cells for a prolonged period of time in a state that showed remarkable structural resemblance and physiological responsiveness to that found in vivo. Three‐dimensional outgrowths from dissociated single epithelial cells and/or small aggregates of epithelial cells were obtained which resembled structures actually found within the prostate gland, as determined by histological and visual examination of the cellular growths present within the gels. In addition, the responsiveness of the cells in the collagen gel cultures to various hormonal additives, including insulin, testosterone, prolactin, and estradiol correlated closely to the manner in which these cells have been shown to respond in vivo. The general characteristics of growth of the cells in the collagen gel cultures, the effect of various sera and different pH levels upon growth, and the ability of the cells to produce acid phosphatase were also investigated.
Two‐dimensional electrophoresis of proteins from different lobes of the rat prostate and seminal vesicle
Authors: Gerhardt P. , Mevåg B. , Rui H. , Purvis K. , Tveter K. J.
Published: February 2007

Two‐dimensional ISO‐DALT electrophoresis of cytosols and secretions from various lobes of the rat prostate gland and seminal vesicle reveals major differences in intracellular and secretory protein patterns. This study confirms a previous study utilizing one‐dimensional electrophoresis.

The dorsal lobe and coagulating gland appear to secrete predominantly relatively basic proteins (molecular mass, MM, 70,000–200,000 daltons, pI > 7) in contrast to the ventral lobe, which secretes proteins of a more acidic character (pI 4–5). The majority of proteins in the latter case appear to represent subunits of the major secretory protein of the rat ventral prostate, prostatein. At least one secretory protein is relatively specific for the lateral lobe (MM 16,000 daltons, pI 4.5). The vesicular secretion also contains relatively greater quantities of basic proteins than acidic but with varying molecular mass (12,000–100,000 daltons).

This study extends the search for specific protein markers for different lobes of the rat accessory sex glands and provides additional biochemical data which can be exploited in the future to isolate selected secretory proteins on a large scale for antibody production.
Establishment of a long‐term adenocarcinoma of the prostate cell line in the nude mouse
Authors: Graham S. D. , Poulton S. H. , Woodard B. H. , Lyles K. W. , Paulson D. F. , Linder J.
Published: February 2007

There are few established human prostatic adenocarcinoma cell lines in existence. Most established lines are nonfunctional and hormonally insensitive. A human prostate adenocarcinoma (9479) has been serially transplanted for more than 4 years in athymic nude mice. The tumor is estrogen and androgen insensitive, is transplantable between mice with a high rate of success. The tumor does not produce enzymatically measurable acid phosphatase, but does produce immunologically identifiable acid phosphatase. Not only has the tumor retained its original morphology, it also appears to produce a factor producing hypophosphatemia. Current studies in regards to the endocrinological aspects of this tumor are in progress. We propose that acid phosphatase is produced, but in an altered form.
Changes of cytosol proteins in the ventral and dorsolateral prostates of rats during sexual maturation: Immature prostate‐abundant proteins as detected by polyacrylamide gel electrophoreses
Authors: Wada Fumio , Nishi Nozomu , Muguruma Yasuyoshi , Tanaka Yukio , Matuo Yuhsi
Published: February 2007

Cytosol proteins in the ventral and dorsolateral prostates of rats from four to 31 weeks of age were analyzed by SDS‐electrophoresis. By comparing the relative contents (% of the total protein), it was found that in addition to the known major proteins which became abundant with age, there were several species abundant in the sexually immature prostates: (1) Ventral prostate: two kinds of secretory proteins with apparent molecular weights of about 31,000 (31K) and 67,000 (67K) and five kinds of nonsecretory proteins (42K, 57K, 58K, 80K and 84K) were abundant at weeks 4‐5; the most susceptible species was 80K, whose content at week 4 decreased to about one tenth at week 31. (2) Dorsolateral prostate: a nonsecretory protein (41K) and 14.4K, 34K, 80K, and 85K, which were distributed into the secretory and nonsecretory fractions, were abundant at weeks 4‐7; the most susceptible species was 80K, whose content at week 4 decreased to about one tenth after week 11. Total contents (content/100 g body weight) of all the protein species increased by aging in either prostate; the most susceptible species were 13K in the ventral prostate and 120K in the dorsolateral prostate, whose total contents increased 90‐100 times during sexual maturation.
Androgen‐repressed messages in the rat ventral prostate
Authors: Montpetit Michael L. , Lawless Kenneth R. , Tenniswood Martin
Published: February 2007

Poly (A)+ RNA from the prostates of both intact and castrated rats was translated in a message‐dependent reticulocyte lysate, and the translation products were electrophoresed on SDS/polyacrylamide gels. Fluorography of these gels showed the expected disappearance, after castration, of the prostate steroid‐binding proteins as well as a number of other androgen‐dependent proteins. Two major (Mr 40,000 and 45,000) and several minor proteins appeared in the translation products of the castrated rat prostate RNA. Criss‐cross liquid hybridization analysis between prostate poly (A+) RNA from intact and castrated rats also showed the disappearance of the abundant prostate steroid‐binding protein sequences after castration and the synthesis of several new low to medium abundance sequences. Northern hybridization experiments demonstrated the presence of at least two, and possibly four androgen‐repressed poly (A)+ RNA sequences. The most prominent of these, an RNA of 2,000 nucleotides, appeared within 2 days of castration, reaching a maximum on day 4 at a level approximately 400 times greater than the normal level. The other major sequence (a sequence of 1,000 nucleotides) appears after 4 days, reaching a peak between days 8 and 11. Sequences similar to these new RNAs could play an important role in the long‐term resistance of prostatic cancer to hormone therapy in humans.
Proliferative responses of rat ventral prostate: Effects of variations in organ culture media and methodology
Authors: Buchanan Lynn J. , Riches A. C.
Published: February 2007

Effects of variations in organ culture media and methodology on the proliferative activity of rat ventral prostate and its response to testosterone were investigated quantitatively by using the incorporation of [125I]‐iododeoxyuridine (125I‐UdR) to monitor DNA synthesis. In serum‐free medium, maximal increases in DNA synthesis occurred when testosterone was introduced during the first 48 hours of the culture. Supplementation of the medium with 5% fetal calf serum did not alter the responses in control or testosterone‐treated cultures, whereas the addition of insulin (3 μg/ml) alone or in combination with serum promoted cell proliferation in testosterone‐free cultures and enhanced the stimulatory effect of testosterone. Unlike grid‐supported cultures, suspension cultures of rat ventral prostate exhibited increased proliferative activity both in the presence and absence of testosterone. Thus, variations in experimental procedure may account for differences in the proliferative activity of rat prostate between organ culture studies.
Zinc and cadmium plasma and erythrocyte levels in prostatic carcinoma, BPH, urological malignancies, and inflammations
Authors: Feustel A. , Wennrich R.
Published: February 2007

Zinc and cadmium in both serum and erythrocytes from patients with prostatic carcinoma of different histologies, BPH, other urological tumors, and pyelonephritis were analyzed by atomic absorption spectrometry. The variance of the results obtained was very high for each group. No significant differences in the Zn or Cd concentration in either the blood plasma or the erythrocytes could be found between any of the different groups of patients. There were also no trends to be seen in the concentrations of these elements in human blood over a period of months. We conclude that the concentration of Zn and Cd in serum or erythrocytes are not an index for the diagnosis or therapy of prostatic carcinoma, BPH, urological malignancy, or inflammations.
The beneficial effects of diphosphonate and piroxicam on the osteolytic and metastatic spread of rat prostate carcinoma cells
Authors: Pollard Morris , Luckert Phyllis H.
Published: February 2007

Transplantable rat prostate adenocarcinoma III cells produce local tumors and osteolytic and osteoplastic lesions and they metastasize through defined lymphatic channels to the lungs in which they produce expanding focal tumors. The bone lesions were prevented by treatments with dichloromethane diphosphonate (C12MDP). Treatment of rats with piroxicam, a nonsteroidal antiinflammatory drug, suppressed to some extent tumor growth, bone destruction, and metastasis. However, simultaneous treatments of rats with both drugs (C12MDP and piroxicam) prevented bone damage and suppressed tumor growth and metastatic spread very significantly without evidence of toxicity.
Correlations between prostate chromatin structure and transcriptional activity and acceptor site distribution
Authors: Davies Peter , Thomas Philip , Manning David L.
Published: February 2007

Androgen‐receptor complexes are intimately involved in the maintenance of rat ventral prostate chromatin in a transcriptionally active structure. The presence or absence of androgens influenced the quantity of transcriptionally active chromatin and the distribution of acceptor sites for androgen‐receptor complexes as probed by endonucleolytic cleavage. After castration, changes in the sedimentation rates of nucleosome oligomers were consistent with the absence of androgen‐receptor complexes and elongating polyribonucleotide chains. These changes were accompanied by decreases in the ability of chromatin released under conditions of minimal nuclease digestion to bind androgen‐receptor complexes and to support incorporation of RNA precursors responsive to androgenic stimulation. Saturation analyses of chromatin and nuclear fractions with partially purified androgen‐receptor complexes revealed two affinity classes of acceptor sites. After castration, alterations in the intrachromatin distribution of acceptor sites were consistent with their redeployment into areas of decreased nuclease sensitivity, as previously shown for androgen‐responsive genes.
Development of a model for the induction of estrogen‐related prostatic hyperplasia in the dog and its response to the aromatase inhibitor 4‐hydroxy‐4‐androstene‐3,17‐dione: Preliminary results
Authors: Habenicht Ursula‐F. , Schwarz Klaus , Schweikert Hans‐U. , Neumann Friedmund , Fathy Etreby M. El
Published: February 2007

Although the presence of the testes is an absolutely necessary prerequisite for benign prostatic hyperplasia (BPH) to occur, the role of androgens in the cause of BPH is still controversial. There are increasing signs for a decisive role of estrogens in that connection. We treated castrated beagle dogs of known age with androstenedione (an androgen that can be aromatized) and with the aromatase inhibitor 4‐hydroxyandrostendione. Six or 9 months of treatment with androstenedione resulted in a BPH characterized by typical androgenic effects—ie, hyperplasia and hypertrophy of the epithelium—and by typical estrogenic effects—, stimulation of the stroma, especially of the smooth muscles, and cystic enlargement of the tubules. These estrogen‐related effects could be clearly antagonized by the simultaneous treatment with the aromatase inhibitor 4‐hydroxyandrostenedione. The hyperplastic effects on the epithelium were also partly antagonized by the aromatase inhibitor. Our preliminary results further strengthen the effectiveness of aromatase inhibitors as an alternative treatment of human BPH, which is thought to be predominantly a stromal disease.
Lobe‐specific distribution of a 20,000‐dalton nonhistone protein in the dorsolateral prostate of rats
Authors: Matuo Yuhsi , Nishi Nozomu , Tanaka Yukio , Muguruma Yasuyoshi , Tanaka Koichiro , Wada Fumio
Published: February 2007

Distribution of an androgen‐dependent, 20,000‐dalton nonhistone protein with a pI of about 11.5 (20K‐NHP) was examined by electrophorectic techniques. Nuclei of the brain, liver, spleen, skeletal muscle, lung, and thymus of rats contained a negligible amount of 20K‐NHP, whereas 20K‐NHP was distinctly detectable, in different relative amounts, in the nuclei of the male accessory sex organs, with the dorsolateral prostate having the highest relative content (100%), followed by the coagulating gland (≈ 16%), the ventral prostate (≈ 6%), and the seminal vesicle (≈ 2%). There were heterogeneous distributions of cytosol components, acid phosphatase isozymes, and nonhistone proteins in the dorsolateral prostate. Zinc was localized in the lateral lobe, and fructose and glucose were in the dorsal lobe. Cytosol proteins with pI 7.5, 8.2, and 8.5 were abundant in the dorsal lobe, and proteins with pI 7.4 and 8.0 in the lateral lobe. Acid phosphatase isozymes with pI 7.1, 7.4, 7.7, and 8.0 were abundantly distributed in the lateral lobe. Of the nonhistone proteins, 20K‐NHP showed the highest content both in the lateral lobe and in the dorsal lobe. It was found that 20K‐NHP was more abundantly distributed in the lateral lobe (maximally four times higher) than in the dorsal lobe. The heterogeneous distribution of 20K‐NHP in the dorsolateral prostate was strikingly similar to that of zinc. It appears, therefore, that 20K‐NHP is closely related to dorsolateral prostate zinc content.
Electrophoretic marker of differentiated human prostate secretory epithelial cells
Authors: Bozhok Y. M. , Kireeva S. S. , Tavokina L. V.
Published: February 2007

Electrophoretic analysis of primordial human prostate epithelium, glandular secretory epithelium of prostate and other human tissues revealed a marker characteristic of differentiated secretory prostate cells. Being probably neither protein nor lipid in chemical nature, this marker reacted in a peculiar way with Amido Black 10B. The marker was shown to be present in prostatic secretory substance.
In vitro stimulation by prostate extracts of rat ventral prostate stromal and epithelial cell division
Authors: Anderson Ken M. , Rubenstein M.
Published: February 2007

We examined the effect of prostate cell extracts on the replication of highly enriched rat ventral prostate stromal and epithelial cells cultured in RPMI‐1640. Extracts from normal rat prostates completely inhibited cell division in both fractions, while a 10% (v/v) extract of Dunning R‐3327G adenocarcinoma inhibited replication of stromal cells but permitted that of epithelial cells. The cytoxic effect of prostate extracts was dialyzable, heat stable, unaffected by proteases, soluble in acid/alcohol, and insoluble in chloroform. These properties are consistent with those of polyamines incubated in the presence of fetal calf serum.

Dialyzed extracts from Dunning adenocarcinomas, and from human benign hypertrophic and carcinomatous prostates stimulated rat prostate stromal and epithelial cell division, in keeping with other reports of “growth factors” in prostate tissue. This mitogenic activity was stable to temperature (70°C, 4 hours), and marginally if at all affected by exposure to trypsin or to pronase coupled to Sephadex. Short‐term culture of separated prostate cells should provide a useful assay system for detecting putative autocrine or paracrine stromal and/or epithelial cell growth factors and identifying suspected homo‐ or heterotypic cellular interactions in normal and diseased prostates.
Quantitative relationships between cytosol and nuclear estrogen and progesterone receptors in the R3327 prostatic carcinoma of rats treated with diethylstilbestrol
Authors: Mobbs B. G. , Johnson I. E.
Published: February 2007

Estrogen and progesterone receptor (ER, PgR) were quantitated by Scatchard analysis in cytosolic and nuclear extracts of R3327H prostatic carcinomas from rats injected with 100 μg diethylstilbestrol or with vehicle for 1–3 weeks. Total tissue ER concentrations were less than 80 fm/mg DNA in control tumors and were not significantly higher in treated tumors: however, in the latter, a significantly higher proportion (73 ± 16%) was associated with the nuclear fraction than in the control tumors (<33%).

Mean PgR concentrations were more than seven‐fold higher in treated than in control tumors, and approximately 25% of the total was associated with the nuclear fraction in both treated and control tumors, under the assay conditions used. There was a strong linear correlation between nuclear ER and PgR concentrations.

These data indicate that although ER concentration in these tumors was low compared with that in female target organs, it was functional in its ability to associate with the nuclear fraction and induce synthesis of an estrogen‐induced protein (PgR) in proportionate amounts.
Anatomy and histology of the musk shrew (Suncus murinus) prostate
Authors: Hijikata Takao , Saito Hiroshi , Yohro Takeshi
Published: February 2007

Gross anatomy and the light and electron microscopic characteristics of the musk shrew (Suncus murinus, Insectivora) prostate are described. The prostate is a pair of compound tubuloalveolar glands with one main excretory duct for each gland. Each gland is divided into ventral and dorsal lobes. The tubuloalveoli are larger in diameter and the secretory cells are lower in the ventral than in the dorsal lobes. Probable spontaneous release of secretory granules and accumulation of secretory material in secretory lumina are only observed in the ventral lobes. Secretory material is often crystallized in the secretory lumina. The epithelium of excretory ducts consists of mucous‐type secretory cells and the boundary between this epithelium and the glandular epithelium is complex. The glandular epithelium consists of secretory and clear cells. This report illustrates that the structure of the prostate of musk shrew is unique among mammals.
A wide range of sensitivities to androgens develops in cloned shionogi mouse mammary tumor cells
Authors: Labrie F. , Veilleux R.
Published: February 2007

Clones obtained in soft agar from a Shionogi mouse mammary carcinoma show marked heterogeneity of growth characteristics and sensitivities to androgens. These data pertain to spontaneous growth in the absence of androgens, maximal response to dihydrotestosterone (DHT) and Km values of the stimulatory action of DHT ranging from 0.008 to 10 ng/ml (1,250‐fold range). Following 13 months in culture in the presence of 10 nM DHT, recloning of one original cell clone led to an even greater variation of androgen‐free growth and of the maximal responses to DHT, while the Km values of DHT action ranged from 0.05 to 10 nM (200‐fold range). The present demonstration of a marked heterogeneity of Km values of DHT action in subpopulations of tumors grown in a controlled environment has major implications for the efficient antihormonal treatment of androgen‐sensitive diseases such as prostate cancer. Such data indicate that cell clones having a high degree of sensitivity to DHT (androgen‐hypersensitive) can continue to grow in the presence of castration levels of androgens, thus suggesting that an antiandrogen is required in order to achieve a more complete androgen blockage and to induce a regression of these androgen‐hypersensitive tumors.