Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have searched for tissue-specific binding of 5alpha-androstan-17beta-ol-3-one (5alpha-dihydrotestosterone; 5alpha-DHT) in cytosols prepared from 25 surgically obtained benign prostatic hypertrophy (BPH) samples and in 3 tissue specimens containing prostate cancer cells. The distinction between steroid-receptor complexes and ligand binding to serum sex hormone-binding globulin (SHBG) was facilitated by combination experiments involving both sucrose gradient ultracentrifugation and agar gel electrophoresis. Gradient analysis of a cytosol prepared from a cervical lymph node (CLN) containing metastatic prostate tissue, revealed both 8-S and 4-S forms of high affinity (charcoal stable) 5alpha-[3H]DHT binding. When electrophoresis was performed on gradient fractions from these zones, anodally migrating steroid-receptor complexes were found only in the 8-S peak, the 4-S region containing radioligand bound to cathodally directed SHBG. In similar experiments with two BPH samples heavily invaded with prostate cancer cells only a single 4-S peak of radioligand binding was detected. Its multicomponent nature was uncovered electrophoretically when, in addition to SHBG, saturable, androgen binding molecules appeared anodally. Their incomplete resolution from SHBG on a gradient might have prevented their identification had this been the only method used. In contrast to the cancer-containing tissues, no saturable 5alpha-[3H]-DHT binding, other than that to SHBG, was detected in any of the BPH samples analysed. It is considered that, of the methods currently available, agar gel electrophoresis may be particularly useful for further investigations into the possible multicomponent nature of androgen binding of tissue origin in the human prostate.
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PMID:Steroid receptors in the human prostate. Detection of tissue-specific androgen binding in prostate cancer. 84 8

A case-control study of prostatic cancer was carried out to examine the association between selected physical characteristics and factors related to sexual development and behaviour and the risk for this disease. In consideration of an endocrinologic mechanism for these putative risk factors, the association between selected factors and serum hormone level in a comparison group, free of prostate cancer, was also examined. One-hundred cases and 113 controls were included for study. An elevated risk for prostatic cancer was found for those currently married (odds ratio (OR) = 4.0), those who had been married once (OR = 2.8), and those who were currently practising a religion (OR = 2.0). Compared to subjects with one child, those with more than one child and those with no children were more common among cases than controls. Prostatic cancer risk was associated with large body size and, in particular, with greater weight (p < 0.01). Early age at attainment of adult height was also associated with prostatic cancer risk (p < 0.01). Only moderate associations were found between increased frequency of sexual intercourse and prostatic cancer risk. The levels of testosterone (T), dihydrotestosterone, salivary testosterone and T/SHBG (sex hormone binding globulin) did not vary with age. Older men had higher oestradiol levels. Further, little association between hormone levels and risk factors was found, except for married subjects having increased serum androgens (p < 0.05) and heavy subjects having decreased serum androgens (not significant).
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PMID:Physical characteristics and factors related to sexual development and behaviour and the risk for prostatic cancer. 146 69

To determine whether endocrine factors influence the volume of benign prostatic hyperplasia (BPH), 23 hormonal factors were measured in the serum of 64 men ages 42 to 71 years with low volume prostatic cancer and these levels were correlated with the volume of benign hyperplastic tissue in their radical prostatectomy specimens. With age there was a significant increase in the volume of BPH. Also with age there was a significant decrease in the serum levels of free testosterone, androstenedione, dehydroepiandronsterone (DHA), dehydroepiandronsterone sulphate (DHA-S), delta 5-androstenediol, and 17-hydroxypregnenolone, and a significant increase in sex hormone-binding globulin (SHBG), LH, and FSH. When BPH volume and hormone levels were corrected for age, BPH volume correlated positively with free testosterone, estradiol, and estriol. These data indicate that with age patients with larger volumes of BPH have higher serum androgen and estrogen levels suggesting that serum androgen and estrogen levels may be factors in the persistent stimulation of BPH with age. If so, therapeutic attempts at lowering plasma testosterone levels, reducing estrogen levels, or blocking androgenic stimulation through other mechanisms may interfere with the progression of BPH with age. Conversely, the fact that androgen production declines gradually with age may explain the observation that only 20 to 30% of men who live to age 80 require surgical treatment for urinary obstruction from BPH.
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PMID:Influence of age and endocrine factors on the volume of benign prostatic hyperplasia. 170 42

The possible relationship between changes in peripheral hormone levels and the occurrence of prostatic pathology was studied in a case-control study, involving estimation of various plasma hormones in 368 Dutch and 258 Japanese men, who were grouped as controls and patients with benign prostatic hyperplasia, focal prostatic carcinoma, or clinically evident prostatic carcinoma. Results of a number of previous, smaller studies concerning interrelationships between hormone levels in elderly men were confirmed within the Dutch and Japanese groups. Plasma levels of testosterone and estradiol were significantly lower in the Japanese men, when compared with those in Dutch men. Probably as a result of this difference in testosterone levels, the ratio between serum levels of testosterone and sex hormone-binding globulin (SHBG) was decreased in the Japanese men, while the ratio between the concentrations of dihydrotestosterone and testosterone was increased. These differences were also found when results from Japanese subgroups (controls and patients with prostate pathology) were compared with those from the Dutch subgroups. There were no significant differences in plasma androgen levels between Japanese or Dutch prostate cancer cases and their respective control subgroups. These findings do not support a correlation between the lower plasma testosterone levels and a lower incidence of prostate cancer in the Japanese men. Furthermore, no significant differences were found between salivary levels of testosterone or the ratio between testosterone and SHBG in the various Dutch subgroups. In Japanese benign prostatic hyperplasia patients, the testosterone to SHBG ratio was significantly increased. In conclusion, the results of this retrospective, cross-sectional study do not indicate that hormonal levels play a primary role in the origin or promotion of prostatic abnormalities. The finding of a lower plasma testosterone in the Japanese men, however, remains suggestive, warranting a more extensive prospective study.
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PMID:Peripheral hormone levels in controls and patients with prostatic cancer or benign prostatic hyperplasia: results from the Dutch-Japanese case-control study. 171 11

The binding of human sex hormone-binding globulin (SHBG) to a human prostatic cancer cell line (LNCaP) and the results of that binding were examined. Membranes derived from LNCaP cells bound unliganded SHBG on two sets of sites whose affinities were: Ka1 = 3.1 +/- 1.6 x 10(10) M-1 and Ka2 = 8.7 +/- 4.3 x 10(6) M-1. Intact cells also bound SHBG, but even after 6 h, less than 10% of specifically bound SHBG was internalized. This observation speaks against a role for the membrane binding of SHBG in steroid transport across cell membranes. When LNCaP cells were prebound with SHBG, addition of dihydrotestosterone or estradiol resulted in a dose-dependent increase in intracellular cAMP. SHBG in the absence of steroids or dihydrotestosterone in the absence of SHBG was without effect. 2-Methoxyestradiol, a steroid metabolite without biological activity, but which binds to SHBG more tightly than does estradiol, was also without effect. These observations demonstrate a potentially important role for SHBG as a regulator of cell function. They also demonstrate an additional mode of action of steroid hormones, one that does not require that the steroid interact with a steroid receptor.
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PMID:Biologically active steroids activate receptor-bound human sex hormone-binding globulin to cause LNCaP cells to accumulate adenosine 3',5'-monophosphate. 216 70

Endogenous androgens have been suggested as determinants of risk of prostatic cancer. To examine this possibility, baseline sex hormone levels were measured in 1008 men ages 40-79 years who had been followed for 14 years. There were 31 incident cases of prostatic cancer and 26 identified from death certificates with unknown dates of diagnosis. In this study, total testosterone, estrone, estradiol, and sex hormone-binding globulin were not related to prostate cancer, but plasma androstenedione showed a positive dose-response gradient. Age-adjusted relative risks of prostatic cancer for low (0-2.2 nM), middle (2.3-3.1 nM), and high (3.2+ nM) tertiles of androstenedione were 1.00, 1.34, and 1.98, respectively (P trend less than 0.05). The linear gradient of risk persisted after adjustment for age and body mass index. If confirmed, these data suggest that androstenedione might increase the occurrence of clinically manifest prostatic cancer.
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PMID:A prospective, population-based study of androstenedione, estrogens, and prostatic cancer. 229 51

The effects of long term GnRH treatment with the biodegradable depot formulation of ICI 118.630 on hormone levels and spermatogenesis were investigated in 18 males with advanced prostate cancer. Plasma levels of FSH, LH, testosterone, DHEA-S and SHBG were monitored at regular intervals. The drug suppressed FSH, LH and testosterone significantly and did not affect DHEA-S and SHBG plasma levels. Tissue specimens for histologic assessment and quantitative analysis of germinal cell types were obtained at secondary orchidectomy in 16 patients immediately following GnRH analogue treatment. Germinal cell maturation was arrested at the spermatogonial stage. In two patients discontinuing treatment histologic assessment of secondary orchidectomy specimens 9 and 10 months after the last GnRH analogue depot injection resulted in germinal cell maturation to late spermatids in part of the tubule cross sections. These results indicate that long term administration of the GnRH analogue fails to produce complete testicular sclerosis and spermatogenic arrest might be reversible.
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PMID:Effects of long term GnRH analogue treatment on hormone levels and spermatogenesis in patients with carcinoma of the prostate. 297 2

We have observed that familial factors have a decided influence on the plasma content of sex steroids in men both in the general population and in men of families with prostatic cancer. The contribution of genetic and nongenetic familial factors on the variation of plasma sex steroid content and action has now been investigated in 75 pairs of normal male monozygotic (MZ) twins and 88 pairs of dizygotic (DZ) twins. Zygosity was determined by measuring ten blood proteins and enzymes. The mean plasma values for testosterone (T), dihydrotestosterone (DHT), estradiol (E2), estrone (E1), and 3 alpha-androstanediol glucuronide (3 alpha-diol G), free T, LH, FSH, SHBG, age, and degree of adiposity were all similar between the groups of twins. Familial factors (P less than 0.01) accounted for 50% or more of the variation in plasma hormone levels in MZ twins (3 alpha-diol G, 84%; T/DHT, 70%; T, 63%; E1, 63%; free T, 61%; E2, 57%; DHT, 56%; LH, 55%; and FSH, 54%) except for SHBG, which was 30%. The familial influence was greater in MZ twins than in DZ twins for all measurements except for SHBG. The heritability of the variation of hormone levels in plasma was determined from the equation: 2[rMZ(intraclass correlation) - rDZ]. Genes regulate 25% to 76% of the total variation of plasma content of the hormones except for DHT (12%) and SHBG (less than 1%). Genetic regulation of tissue DHT formation was suggested by observing a 48% genetic effect on the plasma content of 3 alpha-diol G.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Quantitating genetic and nongenetic factors that determine plasma sex steroid variation in normal male twins. 309 56

Seventy-eight patients with cytologically and/or histologically confirmed prostatic cancer were randomly allocated to orchidectomy (ORX, n = 37) or combined intramuscular and oral estrogen treatment (ESTR, n = 41). Serum levels of testosterone (T), 17 alpha-hydroxyprogesterone, dehydroepiandrosterone, dehydroepiandrosterone sulfate, total estrone (tE1; sum of unconjugated and conjugated estrone, greater than or equal to 85% estrone sulfate), cortisol, luteinizing hormone, follicle-stimulating hormone, prolactin, growth hormone, sex hormone-binding globulin (SHBG), and albumin were determined prior to treatment and 12, 24, and 36 months after initiation of treatment. Fifty patients responded to treatment or had stable disease, and 28 did not respond (12 in the ORX and 16 in the ESTR group). There was no association between pretreatment hormone or protein levels and outcome of the treatment, neither in the total material nor within either of the two treatment subgroups. Significantly higher pretreatment levels of cortisol and prolactin and significantly lower levels of T, tE1, and albumin and a significantly lower T/SHBG-ratio (index on biologically active T) were found in patients with metastatic disease, compared with the patients without metastases. There was no association between testicular or adrenal androgens, SHBG, T/SHBG, and albumin values during treatment and the clinical outcome. The differences found between metastatic and nonmetastatic disease probably simply reflect the more stressful and catabolic condition and generally poorer health in patients with disseminated malignant disease. Furthermore, the study does not lend any support to the hypothesis that indicates an important role of adrenal "rest androgen" in prostatic cancer tumor growth.
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PMID:Prognostic value of serum hormone concentrations in prostatic cancer. 321 6

Cytoplasmic and nuclear receptor sites of the prostate will be determined for a qualitative information about the pattern of specific bindings. Their qualitative evaluation and their selective suppression will give an idea about the hormonal influence and regulation in prostatic tissue. These investigations are performed in some cases of prostatic cancer. The difficulty of tissue preparation is caused by the individual distribution of collagen tissue in prostatic cancer which will decide the yield of purified receptor sites. Besides the elemination of unspecific binding sites like SHBG and albumin is an evidence for the value of a method. According to high amount of binding sites the most effective preparation of patients before a tissue biopsy is discussed. For the clinical application the DCC test in case of cytoplasmic sites and the exchange test for nuclear sites seem to provide a suitable method. Performing gelfiltration and additional test with denatured material is necessary because of the similar size of SHBG and receptor complexes interfering the results.
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PMID:[Possibilities for the evaluation of receptor sites in benign prostatic hyperplasia and carcinoma of the prostate (author's transl)]. 616 65


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