Altered Blood Androgens in Elderly Men With Prostate Hyperplasia.

Horton, Richard; Hsieh, Paul A.; Barberia, Juan M.; Pages, Louisa; Cosgrove, Malcolm D.

doi:10.1210/jcem-41-4-793

Cited by 89 publications

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“…Reduced MCR of sex steroids in elderly men is probably the result of increased sex hormone-binding globulin levels (21) as well as reduced cardiac output and splanchnic blood flow in the older man. A significant reduction in the production rate ofboth testosterone and 3adiol is observed in the elderly male as a result (16) and the production rate of DHT, which is not reduced (20).…”

Section: Methodsmentioning

confidence: 90%

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Alteration in the metabolism of dihydrotestosterone in elderly men with prostate hyperplasia.

Morimoto¹,

Edmiston²,

Horton³

1980

J. Clin. Invest.

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A B S T R A C T In vivo androgen kinetics were determined in six young (21-49 yr) and elderly men (62-77 yr) with prostate hyperplasia (BPH). Steadystate infusions of [14C]testosterone and [3H]androstanediol (3adiol) were given, which allowed determination of the conversions testosterone -* dihydrotesterone (DHT) ti 3adiol. These infusions also yield metabolic clearance data which, together with measurement of nonisotopic steroid levels, yield estimations of blood production rates. The production rate for testosterone was 6.04±+1.66 vs. 3.69+±0.62 mg/d, whereas the production rate for 3adiol was 319±57 and 193+34 ,tg/d (P < 0.05 both groups). The irreversible conversion rate of testosterone to DHT was 3.1+0.4 and 3.5±0.9% (NS). The back conversion of 3adiol to DHT was high (68+25 vs. 81±+17, NS) indicating that 3adiol might cause BPH as a result of conversion to DHT in vivo. The conversion of DHT to 3adiol is reduced in the elderly group (15.8±2.6 and 6.3+1.4, P < 0.001). Since DHT formation in the prostate is a key event in development of BPH and blood DHT appears to be a measure of extrasplanchnic sexual target tissue activity, our in vivo studies suggest that the tissue increase in DHT may result from reduced metabolism and the activity of 3a-oxidoreduction favors the oxidative pathway in elderly men.

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Section: Methodsmentioning

confidence: 90%

“…The concenitrationi of sex steroids were measured by immunoassay methods described from our laboratory (15)(16)(17). Samples were taken before the infusion every 20 min (three times) to minimize short-term episodic fluctuation in concentrations.…”

Section: Methodsmentioning

confidence: 99%

Alteration in the metabolism of dihydrotestosterone in elderly men with prostate hyperplasia.

Morimoto¹,

Edmiston²,

Horton³

1980

J. Clin. Invest.

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“…To estimate the activity of 5␣-reductase, which catalyzes the conversion of testosterone to DHT, testosterone and DHT have been quantified in biological samples (2)(3)(4). Because of their lipophilic properties, they are usually found in the conjugated form, i.e., linked to a hydrophilic sulfuric moiety or ␤-glucuronic acid, which are excreted mainly (Ͼ95%) in human urine.…”

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confidence: 99%

“…These are used to define the efficiencies of nucleic acid extraction, reverse transcription, amplification, and detection and to quantify the effects of nonspecific inhibitors. Examples include the "Qs" controls included in Amplicor PCR assays (Roche Molecular Systems Inc.) (1 ) and the "Qa, Qb, Qc" controls used in Nuclisens assays (Organon Technica) (2 ). Control constructs (RNA or DNA) are derived from the nucleic acid sequence that the test method is designed to assay and span the primer binding sequences used in the assay.…”

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confidence: 99%

Rapid HPLC-Electrospray Tandem Mass Spectrometric Assay for Urinary Testosterone and Dihydrotestosterone Glucuronides from Patients with Benign Prostate Hyperplasia

Choi¹,

Kim

Chung³

2003

Clinical Chemistry

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by the locus-specific primer is directly subjected to TaqI digestion and is analyzed on an agarose gel without radioisotopic hybridization. It also appears to be more accurate because all three distinct chimeric CYP21P/ CYP21 genes had 3.2-kb fragments (Fig. 1C, lanes 3 and 4). Simply assuming that the 3.2-kb fragment from conventional Southern analysis (6 ) is a deletion of the CYP21 gene has been shown to be incorrect. The authors of one report have stated that the 3.2-kb fragment analyzed by Southern blotting identified a fused CYP21 gene, but in this study, Southern blotting was performed with radioisotope hybridization and a different endonuclease (8 ).In conclusion, the coexistence of 9.3-and 3.2-kb fragments is consistent with a chimeric CYP21P/CYP21 gene. The method of analysis we have described is a novel tool for identification of such a molecule. These chimeric genes were found to occur frequently in CAH caused by steroid 21-hydroxylase deficiency in a Taiwanese (ethnic Chinese) population. The development of benign prostatic hyperplasia (BPH) is dependent on androgens, primarily dihydrotestosterone (DHT) (1 ). To estimate the activity of 5␣-reductase, which catalyzes the conversion of testosterone to DHT, testosterone and DHT have been quantified in biological samples (2-4 ). Because of their lipophilic properties, they are usually found in the conjugated form, i.e., linked to a hydrophilic sulfuric moiety or ␤-glucuronic acid, which are excreted mainly (Ͼ95%) in human urine. Despite reports of a close association between BPH and testosterone and DHT (1-4 ), to our knowledge, there is no published simultaneous quantitative data for these metabolites as their glucuronides in the urine of patients with BPH.The major problem associated with quantification of total steroids is incomplete hydrolysis, attributable mainly to the matrix effects of urine on the efficiency of enzymatic hydrolysis, which reduces the reproducibility of the assay (5,6 ). Given that it is often necessary to analyze many samples in a short time with good sensitivity and reproducibility, system throughput is a critical issue for many clinical mass spectrometry (MS) groups. In 322 Technical Briefs

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“…High tissue levels of dihydrotestosterone (DHT) have been reported in benign hyperplasia (Siiteri & Wilson, 1970) and circulating plasma levels of this steroid have been found to be higher in patients with BPH than in normal subjects (Horton et al, 1975;Vermeulen & Desy, 1976;Ghanadian et al, 1977). However, this latter finding has not been detected by some investigators (Harper et al, 1976).…”

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confidence: 98%

Serum testosterone and dihydrotestosterone in carcinoma of the prostate

Ghanadian¹,

Puah²,

O'donoghue³

1979

Br J Cancer

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Summary.-Serum testosterone (T) and dihydrotestosterone (DHT) were measured by a sensitive and reliable radioimmunoassay in 42 normal subjects and 33 agematched patients with carcinoma of the prostate. The mean +s.e. for serum testosterone in normal subjects was 16-74h076nM and the corresponding value for patients with carcinoma was 20-94±1-48nM. Statistical analysis of the results showed a significant increase in T level in patients with carcinoma of the prostate (P<001). In contrast, there was no difference in DHT concentration between the two groups, values being 2-43±0-09 and 206±009nM for normal subjects and patients respectively.The means +s.e. for T/DHT ratio in controls and patients were 68+O0-2 and 12-8±1*3 respectively. The difference was highly significant (P<0001). The wide range of variation for T in patients with carcinoma would suggest that although mean T is higher in these patients, this measurement alone is of little practical value, whereas T/DHT ratio is a more reliable parameter in evaluating the androgen changes in these patients. The significance of these findings in relation to the aetiology of the disease is discussed.

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Altered Blood Androgens in Elderly Men With Prostate Hyperplasia.

Cited by 89 publications

References 0 publications

Alteration in the metabolism of dihydrotestosterone in elderly men with prostate hyperplasia.

Alteration in the metabolism of dihydrotestosterone in elderly men with prostate hyperplasia.

Rapid HPLC-Electrospray Tandem Mass Spectrometric Assay for Urinary Testosterone and Dihydrotestosterone Glucuronides from Patients with Benign Prostate Hyperplasia

Serum testosterone and dihydrotestosterone in carcinoma of the prostate

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