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At least 955 records · Page 53Linked to original sources
PubMed2005

Risk-adapted androgen deprivation and escalated three-dimensional conformal radiotherapy for prostate cancer: Does radiation dose influence outcome of patients treated with adjuvant androgen deprivation? A GICOR study.

PURPOSE: Multicenter study conducted to determine the impact on biochemical control and survival of risk-adapted androgen deprivation (AD) combined with high-dose three-dimensional conformal radiotherapy (3DCRT) for prostate cancer. Results of biochemical control are reported. PATIENTS AND METHODS: Between October 1999 and October 2001, 416 eligible patients with prostate cancer were assigned to one of three treatment groups according to their risk factors: 181 low-risk patients were treated with 3DCRT alone; 75 intermediate-risk patients were allocated to receive neoadjuvant AD (NAD) 4-6 months before and during 3DCRT; and 160 high-risk patients received NAD and adjuvant AD (AAD) 2 years after 3DCRT. Stratification was performed for treatment/risk group and total radiation dose. RESULTS: After a median follow-up of 36 months (range, 18 to 63 months), the actuarial biochemical disease-free survival (bDFS) at 5 years for all patients was 74%. The corresponding figures for low-risk, intermediate-risk, and high-risk disease were 80%, 73%, and 79%, respectively (P = .847). Univariate analysis showed that higher radiation dose was the only significant factor associated with bDFS for all patients (P = .0004). When stratified for treatment group, this benefit was evident for low-risk patients (P = .009) and, more interestingly, for high-risk patients treated with AAD. The 5-year bDFS for high-risk patients treated with AAD was 63% for radiation doses less than 72 Gy and 84% for those > or = 72 Gy (P = .003). CONCLUSION: The results of combined AAD plus high-dose 3DCRT are encouraging. To our knowledge, this is the first study showing an additional benefit of high-dose 3DCRT when combined with long-term AD for unfavorable disease.

Age Factors↗
PubMed2006

Suppression of androgen receptor transactivation and prostate cancer cell growth by heterogeneous nuclear ribonucleoprotein A1 via interaction with androgen receptor coregulator ARA54.

The androgen receptor (AR) requires coregulators for its optimal transactivation. Whether AR coregulators also need interacting proteins to modulate their function remains unclear. Here we describe heterogeneous nuclear ribonucleoprotein (hnRNP) A1 as an associated negative modulator for the AR coregulator ARA54. hnRNP A1 selectively suppressed ARA54-enhanced wild-type and mutant AR transactivation via interruption of AR-ARA54 interaction and ARA54 homodimerization. Stable transfection of hnRNP A1 in the LNCaP cells suppressed AR-mediated cell growth and the expression of prostate-specific antigen, and this suppressive effect was abolished by the addition of ARA54-small interfering RNA. Small interfering RNA knockdown of endogenous hnRNP A1 enhanced cell growth and prostate-specific antigen expression in LNCaP cells. These results not only suggest that the loss of hnRNP A1 expression might activate the ARA54-enhanced cell growth and contribute to the prostate cancer progression, but also demonstrate the dual functional roles for ARA54 as an AR coregulator directly and as a mediator for the suppressive effect of hnRNP A1 indirectly. The novel finding that a protein can modulate AR function without direct interaction with AR might provide a new therapeutic approach to battle prostate cancer by targeting AR indirectly with fewer side effects.

3T3 Cells↗
PubMed1988

Monoclonal antibodies against the androgen receptor: recognition of human and other mammalian androgen receptors.

Monoclonal antibodies against the androgen receptor (AR) will provide useful probes for elucidating both the structure and function of this important regulatory protein. Recently, human autoimmune anti-AR sera have been described. The purpose of the current work was to immortalize lymphocytes from the blood of patients with high titer anti-AR antibodies and to produce monoclonal antibodies against the receptor in vitro. Human serum samples (10 microliters) were incubated in high ionic strength buffer (400 mM KCl) for 16 h at 0 C with [3H]Mibolerone-labeled cytosol (100-200 fmol AR) from Dunning tumors. Receptor-antibody complexes were precipitated with goat antihuman immunoglobulin (Ig) antibody. From our 1005 serum samples examined, 5 specimens were detected which precipitated greater than 40% of the AR. These antibodies recognized the AR from human, rat, mouse, dog, steer, chicken, and hamster, but did not recognize estrogen, progesterone, or glucocorticoid receptors. By sucrose gradient analysis in high salt (0.4 M KCl) 1 of the antisera shifted the 4.4S monomeric receptor to 8S, and the others shifted the receptor to 18S. However, all of the antibodies were shown to be IgG class by immunoprecipitation with class-specific second antibodies. Peripheral blood lymphocytes donated by these patients were isolated by histopaque density gradient sedimentation, activated in vitro, transformed with Epstein-Barr virus, and seeded into 96-well plates. From 263 million human lymphocytes plated in 96-well dishes, 1215 wells gave rise to Epstein-Barr virus-transformed lymphoblastoid cells, and 8 of these wells were determined to be anti-AR positive. Cells from 2 of the positive wells were cloned and designated CB54 and UA67, both of which secreted IgG class antibodies against the AR. These 2 monoclonal antibodies have been shown to be highly specific for the AR and to cross-react with the AR from human, rat, and hamster. Studies with the monomeric form of the AR and its proteolytic fragment using sucrose density gradients have suggested that the 2 antibodies recognize different epitopes on the monomeric AR molecule. Furthermore, by Western blot analysis the antibodies have identified the AR as an 118K protein on a sodium dodecyl sulfate gel, which is consistent with our previous findings of the mol wt of the AR.

Animals↗
PubMed1984

Partial androgen resistance associated with secondary 5 alpha-reductase deficiency: identification of a novel qualitative androgen receptor defect and clinical implications.

We studied a family in which three brothers were born with ambiguous genitalia and had poor virilization at puberty. One patient (II-5) required less surgery to repair his hypospadias and is lean, muscular, and hairy compared to his brothers (II-1, II-2). Their adult levels of plasma testosterone (T) range from 765-2250 ng/dl. The plasma T to 5 alpha-dihydrotestosterone (DHT) ratios were 29 (n = 5) in patient II-1, 25 (n = 2) in patient II-2, and 14 (n = 2) in patient II-5, compared to 12 +/- 3 (SD) in normal men. The mean urinary etiocholanolone to androsterone ratios were 1.9 (n = 2) in patient II-1, 2.0 in patient II-2, and 1.3 in patient II-5, compared to 0.87 +/- 0.34 in normal men. The mean urinary ratios of 5 beta-tetrahydrocorticosterone to 5 alpha-tetrahydrocorticosterone were 0.98 (n = 2) in patient II-1, 1.25 in patient II-2, and 0.71 in patient II-5, compared to 0.53 +/- 0.22 in normal men. Genital skin fibroblasts (GSF) from patient II-1 had unusually low 5 alpha-reductase (5 alpha-R) activity (0.3 pmol/mg protein X h; n = 6), but those of patient II-5, a normal brother (II-3), and a sister (II-4; with impaired development of sexual hair) had normal values of 6.5 (n = 2), 9 (n = 3), and 9 (n = 2) pmol/mg protein X h, respectively. The maximum specific DHT receptor-binding activity (Bmax) and the rate constant of dissociation (k) of DHT-receptor complexes in the GSF from each of these individuals were normal, but the apparent equilibrium dissociation constants (Kd) for DHT were 1.16 +/- 0.28 (n = 4) in II-1, 0.39 +/- 0.20 (n = 6) in the sister, and it was 0.19 +/- 0.09 (n = 3) in the unaffected brother and 0.22 +/- 0.09 nM (n = 26) in normal men. The Bmax with the synthetic, nonmetabolizable androgen, methyltrienolone (R1881), and the k of R1881-receptor complexes were normal, but the Kd for R1881 in the GSF of II-1 was 1.4 nM (n = 2), compared to 0.16 +/- 0.05 (n = 8) in normal men, and prolonged exposure to R1881 failed to augment (up-regulate) the basal R1881-binding activity in his cells.(ABSTRACT TRUNCATED AT 400 WORDS)

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed2003

Expression of androgen, estrogen, and progesterone receptors in salivary gland tumors. Frequent expression of androgen receptor in a subset of malignant salivary gland tumors.

The expression of sex hormone receptors in some tumors suggests a role for these receptors in tumor pathogenesis and therapy. Previous studies of the expression of estrogen and progesterone receptors in salivary gland tumors have reported conflicting results. We evaluated the immunohistochemical expression of androgen, estrogen, and progesterone receptors (AR, ER, and PR) in a series of 78 formalin-fixed, paraffin-embedded salivary gland tumors. Immunoreactivity for AR was seen in 14 of 14 carcinoma ex pleomorphic adenomas, 6 of 6 salivary duct carcinomas, and 2 of 2 basal cell adenocarcinomas but in only 2 of 10 acinic cell carcinomas, mucoepidermoid carcinomas, and adenoid cystic carcinomas each. AR expression was distributed evenly between the sexes. ER and PR were expressed in only a few cases of salivary gland tumors. All 26 benign salivary gland tumors were negative for AR, ER, and PR. The uniform expression of AR exclusively in a subset of malignant salivary gland tumors suggests a possible role for AR in the histogenesis and possibly in the clinical management of these malignant salivary gland tumors.

Adenocarcinoma↗
PubMed1979

Anti-androgen TSAA-291. IV. Effects of the anti-androgen TSAA-291 (16 beta-ethyl-17 beta-hydroxy-4-oestren-3-one) on the secretion of gonadotrophins.

Effects of the anti-androgen TSAA-291 on the gonadotrophin secretion were studied. (1) A single subcutaneous or oral administration of TSAA-291 and its caproate induced the ovulation in the proestrous rat of which the spontaneous ovulation was blocked by the treatment with chlorpromazine. (2) A single subcutaneous administration of TSAA-291 at 2.4 mg/kg to the adult male rat induced only a slight elevation in the serum LH and FSH levels at 30 min after the administration. Successive intramuscular administrations of TSAA-291 to the adult male rat for 2 or 4 weeks resulted in significant decreases in the serum LH and FSH levels at high dose levels. A dose-dependent decrease in the serum LH level but not FSH level was observed in the orchiectomized rat. (3) Successive intramuscular administrations of TSAA-291 at high dose levels to the male rat suppressed the plasma testosterone level in the testicular venous blood and general circulation.

Administration, Oral↗
PubMed1978

Androgens and androgen-binding protein in the rat epididymis.

The levels of testosterone, dihydrotestosterone (DHT), 5alpha-androstan-3alpha,17beta-diol and androgen-binding protein (ABP) were measured in various segments of the epididymis from adult rats which had been unilaterally orchidectomized for 4 weeks. On the 'intact' side, ABP concentrations were highest in the caput region. The segmental distribution of DHT closely followed that of ABP with the highest concentration in the caput (40 ng/g tissue) and lowest in the cauda (10 ng/g tissue) epididymidis. There was a high degree of correlation (r = 0.98) between the concentration of DHT in the epididymis and ABP levels. 'Castration' completely abolished the DHT gradient. The levels of testosterone and androstanediol were lower than those of DHT; most was present in the corpus epididymidis. The relative differences were reduced after 'castration'. It is concluded that ABP in the rat epididymis is the primary factor for determining the concentration of DHT in the epididymal fluid.

Androgens↗
PubMed1992

Sensitivity of the vagina and uterus of mice neonatally exposed to estrogen or androgen to postnatal treatment with estrogen or androgen.

Newborn female BALB/cCrgl mice receiving 5 micrograms of testosterone or 0.01 micrograms of diethylstilbestrol daily for the first 5 days of life were examined at various times after secondary exposure to testosterone and 17 beta-estradiol, respectively. Neonatal administration of testosterone induced squamous stratification associated with constant cornification of the vaginal epithelium in intact mice. Later exposure to testosterone suppressed cornification, resulting in superficial epithelial mucification in almost all mice by 4 months of age. However, at 6 months of age, the incidence of mucification dropped to 58%. Cervicovaginal lesions developed in the groups of mice given neonatal testosterone in combination with later testosterone and sacrificed at 4 and 6 months of age. Continuous vaginal stratification was found in 14% of ovariectomized, neonatally diethylstilbestrol-treated mice at 13 months of age. The incidence of this ovary-independent change increased to 40% at 24 months of age. Postnatal estrogen replacement significantly increased the incidence of squamous stratification in these mice. Neonatal diethylstilbestrol treatment alone induced cervicovaginal lesions in 4.5% of ovariectomized mice at 13 months of age; secondary 17 beta-estradiol exposure significantly enhanced the development of lesions to 44%. However, at 24 months of age, there was no difference in the incidence of lesions in ovariectomized, neonatally treated mice with or without the secondary 17 beta-estradiol treatment. These results suggest that the effects of neonatal exposure to a relatively low dose of estrogen, androgen, or related substance may become obvious later in life as a result of later exposure to hormones.

Age Factors↗
PubMed1975

Androgens in breast cancer. III. Breast cancer recurrences years after mastectomy and increased androgenic activity.

To test the hypothesis that increased androgenic activity is involved in breast cancer, the urinary testosterone was assayed in 19 clinically cured breast cancer patients and in 22 patients developing metastases from breast cancer during the same period of observation (5 to 15 years after mastectomy). The levels in the clinically cured patients were near normal whereas those in patients with metastases were significantly above normal.

Age Factors↗
PubMed2001

Use of androgens in patients who have HIV/AIDS: what we know about the effect of androgens on wasting and lipodystrophy.

Decreases in energy, sense of well-being, libido, muscle strength, and muscle mass occur often in patients who have chronic diseases, such as HIV infection. When these symptoms were first recognized in HIV-positive patients, they were thought to be manifestations of HIV infection but may possibly be associated with hypogonadism. Most HIV-infected patients who have hypogonadism have secondary or central hypogonadism, not primary testicular failure. In HIV-infected hypogonadal men, administration of testosterone appears to increase fat-free mass, muscle mass, and quality of life (increased libido, erectile function, and sense of well-being). Similarly, anabolic steroid hormones appear to increase lean body weight and decrease fat content. Although androgens have been used for the treatment of HIV-related wasting and for hypogonadism, many questions remain unanswered, including those regarding the long-term effects, if any, of suppression of luteinizing hormone and follicle-stimulating hormone, as well as the long-term possibilities of malignancy of the prostate and of hepatocellular cancer. Appropriate doses of the various preparations of testosterone and anabolic steroids have not been determined.

Administration, Oral↗
PubMed1990

[The effect of increased production of androgens on the development of body build morphology. Case report of an androgen-active tumor in a monozygotic twin].

The authors present an account on monozygotic twins where in one girl an androgen-active adenoma of the adrenal cortex during early puberty led to the development of the Morphogram of Body Build (Case-report of throughout the period of investigation intact from the hormonal aspect. Four years after resection of the tumour endocrine and anthropometric characteristics of the two sisters were evaluated: the hormonal status of both is normal, the somatic differences are manifested by a different final height, biacromial width and chest circumference. The results are conceived as a precedent for evaluation of risks associated with administration of anabolic steroids in children.

Adenoma↗
PubMedDate not supplied

[Androgen status in rabbits after long-term administration of non-steroid androgen antagonist niftolid].

Niphtholid (25 mg/kg/dl for 60 days) significantly increases the LH and testosterone blood levels but has no marked effect on ++androstenedione and testosterone-estradiol-binding globulin levels in Chinchilla++ mature rabbits. The concentration of latter was elevated against a background of low testosterone and androstenedione and high LH levels in the castrated rabbits. The obtained results show that niphtholid exerts a continuous stimulating and pronounced effect on the rabbit pituitary-gonadal axis and simultaneously prevents the manifestation of suppressing androgen effect on testosterone-estradiol-binding globulin contents in the organism.

Administration, Oral↗
PubMed1986

[Purification of the human prostate androgen receptor. I. Purification of the androgen receptor by affinity chromatography].

The androgen receptor (AR) was purified to establish a new method for measuring AR after producing the antibody for the purified AR. AR was purified from 1,700 g of benign prostatic hypertrophic tissue by combining affinity chromatography of heparin Sepharose CL-6B and of 17 alpha-carboxy-hexamethyl-17-hydroxy-4-androstane-3-one Sepharose 4B. The final purification fraction had the high affinity, low capacity binding to 3H-R 1881 in the presence of 1,000-fold molar excess of triamcinolone acetonide with a dissociation constant of 2.3 nM, showing the binding specificity of AR. Polyacrylamide gel electrophoresis did not reveal any albumin or TeBG mixed in the final purification fraction. These results showed that AR was partially purified, even though the degree of purification was low, around 38 fold calculated by the binding capacity per mg protein.

Aged↗
PubMed1986

[Purification of the human prostate androgen receptor. II. Characterization of the human prostate androgen receptor].

For improved purification of human prostate androgen receptors (AR), the effect of molybdate, NaSCN and heparin on the binding capacity of human prostate cytosol AR was investigated. When 10 mM of molybdate in final concentration was added to cytosol, the increase in the maximum binding sites of AR to 3H-R1881 was approximately 60%, while the dissociation constant was rather increased. With sucrose density gradient centrifugation, the cytosol with molybdate added showed a constant peak of 8 approximately 9 S. However, cytosol not enriched with molybdate did not show any significant peak. These results constitute evidence that molybdate has a stabilizing effect of the AR. When 0.1 approximately 0.5 M of NaSCN was added to the cytosol, the dissociation as well as the association of the 3H-R1881-AR complex showed a tendency to accelerate. However, at a concentration of 0.3M and over NaSCN, the binding capacity of the AR rapidly disappeared. When the NaSCN was removed with gel filtration, the binding capacity of the AR recovered partially. The effect of NaSCN on the AR was therefore different from that on the estrogen receptors. Four mg/ml of heparin accelerated the dissociation of the 3H-R1881-AR complex. Furthermore, with the addition of 4 mg/ml of heparin, the maximum binding sites of AR decreased to 56%. The above results make it clear that molybdate, NaSCN and heparin have various effects on human prostate cytosol AR, which might be applied to the purification of AR.

Cytosol↗
PubMedDate not supplied

[Effect of steroids with anti-androgenic properties on the androgenic and myotrophic activity of testosterone and its various derivatives].

Experiments were conducted on castrated male rats. The effect of antiandrogen 17,17-dimethyl-18-norandrostadien-4,13-one-3 on the androgenic and myotrophic activity of testosterone and of some of its modified analogues, preparations with anabolic action, was studied. The intensity of the antihormonal effects depended not only on the antiandrogen dose used, but also on the dose of the agonist preparation. The author suggests a modification of the method used to assess the biological action of antiandrogens, consisting in a single administration of the "anabolic" preparation with a prolonged action and a 7-day administration of antiandrogen to castrated animals.

Androgen Antagonists↗
PubMed1979

Saliva as a matrix for measuring free androgens: comparison with serum androgens in polycystic ovarian disease.

We report a simple and direct procedure for the measurement of circulating free testosterone concentrations by using saliva as a matrix rather than serum. There is a close correlation between saliva testosterone values measured by radioimmunoassay, calculated values of free testosterone, and free testosterone estimated by equilibrium dialysis. Our method is direct and has the advantage that the biologic fluid can be obtained routinely by noninvasive techniques outside the clinic during a course of therapy. We also show that a single saliva value is of greater diagnostic use than any of the currently used androgen assays. Testosterone was found to be elevated in the saliva of 17 infertility patients diagnosed as having polycystic ovarian syndrome, 14 of these patients were hirsute.

Androstenedione↗