5α-androstane-3β,17β-diol hydroxylating enzymes in stroma and epithelium of human benign prostatic hyperplasia (BPH)

To study the influence of 5 alpha-reductase on the concentration of dihydrotestosterone in prostatic tissue, we measured the activity of this enzyme in stroma and epithelium from 15 normal, 50 hyperplastic, and 20 carcinomatous prostates. Maximum velocity (Vmax) and Km parameters based on the Lineweaver-Burk and Eadie-Hofstee transformations of the Michaelis-Menten equation were related to the stromal and epithelial concentrations of dihydrotestosterone. On the basis of relative Vmax values, there was 6-15 times more 5 alpha-reductase activity in stroma than in epithelium regardless of the histology of the prostate. Stromal enzyme activity also was unique in having a 2- to 5-fold larger mean Km value and greater resistance to competitive and noncompetitive inhibition. Despite the enrichment of 5 alpha-reductase activity in stroma, the dihydrotestosterone concentrations in the stromal and epithelial fractions were very similar. In addition, similar concentrations were found in the stromal fractions of hyperplastic and carcinomatous tissues, notwithstanding a 4-fold difference in the mean Vmax values. This anomaly occurred in association with a large disparity in mean Km values, i.e. 68.3 +/- 1.6 (+/- SE) nmol/L in hyperplasia vs. 23.0 +/- 2.9 nmol/L in carcinoma. The dissociation between parameters of 5 alpha-reductase activity and tissue dihydrotestosterone concentrations was apparent to some extent in benign prostatic hyperplasia, in which the lowest stromal androgen concentrations were found in prostates with the largest Vmax and Km values; also, a rise in stromal Km was almost invariably associated with a proportional increase in Vmax (correlation coefficient = 0.95). These data strongly suggest that the stromal and epithelial forms of 5 alpha-reductase are separate isoenzymes, and that the excess of 5 alpha-reductase in stroma does not promote accumulation of an abnormal amount of dihydrotestosterone. They also imply that both the augmentation of 5 alpha-reductase activity in hyperplastic stroma and the condition of benign hyperplasia of the prostate are mutual consequences of a primary increase in Km.

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“…However, the available evidence suggests that hyperplasia is associated with reduced catabolic activity of this type (19,47).…”

Section: Discussionmentioning

confidence: 93%

Kinetic Parameters of 5α-Reductase Activity in Stroma and Epithelium of Normal, Hyperplastic, and Carcinomatous Human Prostates*

Bruchovsky

Rennie

Batzold

et al. 1988

The Journal of Clinical Endocrinology & Metabolism

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“…Um diese In-vivo-Effizienz der Enzyme genauer abschä tzen zu kö nnen, wurde deren Konzentration (V max ) und Substrataffinität (K m ) im Epithel und Stroma bestimmt. Aus den Daten lassen sich V max /K m -Quotienten bilden, die einen Index fü r die Effizienz der jeweiligen Enzyme darstellen [17][18][19][20][21].…”

Section: Potentielle In-vivo-effizienz Androgenmetabolisierender Enzyunclassified

Die benigne Prostatahyperplasie - das Ergebnis einer altersbedingten Entgleisung der Androgen-Estrogen-Balance?

Weisser

Krieg

1997

Der Urologe A

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Although human benign prostatic hyperplasia (BPH) is the most common tumor in men, its etiology is still unclear. At present, it is only widely accepted that BPH is under the endocrine control of the testes and strongly associated with aging. Therefore, in the human prostate we describe the impact of aging on the activity of various androgen metabolizing enzymes as well as on the endogenous androgen and estrogen levels. Moreover, the inhibition of 5 alpha-reductase by finasteride (Proscar) will be reported. Among all androgen metabolizing enzymes, within the human prostate 5 alpha-reductase is the most powerful one. Most of the androgen metabolizing enzymes undergo a significant age-dependent alteration. For distinct enzymes, the correlation with age is either negative (e.g. 5 alpha-reductase), or positive. Despite a complex pattern of age-dependent alterations, the dominance of 5 alpha-reductase among all androgen metabolizing enzymes is always maintained. This is underlined by a strong accordance between the age-dependent 5 alpha-reductase activity and the corresponding age-dependent endogenous DHT level. In epithelium, both the 5 alpha-reductase activity and the DHT level decrease with age, whereas in stroma not only the 5 alpha-reductase activity is rather constant over the whole age range but the DHT level as well. In contrast to the relatively unaltered DHT content in the stroma of the human prostate, the estrogen content follows an age-dependent increase. On the other side, in epithelium such a positive correlation between the estrogen level and age is not found. Thus, the age-dependent decrease of the DHT accumulation in epithelium and the concomitant increase of the estrogen accumulation in stroma will lead to a tremendous increase with age of the estrogen/androgen ratio in the human prostate. This could be of pathogenetic importance for BPH development if in fact a balanced androgen/estrogen synergism is necessary for the integrity of the normal human prostate. Finally, it is remarkable that the inhibition of 5 alpha-reductase activity by finasteride (Proscar) is significantly stronger in epithelium than in stroma. Therefore, it is conceivable that the global size-reduction of BPH under finasteride treatment is primarily due to the regression of BPH epithelium.

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“…The retained tissue was resuspended in four volumes of Tris buffer (w/v), and defined as stroma. Using this separation procedure, the relative purity of the epithelial as well as the stromal fraction was more than 83%; estimated by measuring acid phosphatase as a marker for epithelial cells and hydroxyproline as a marker for stromal elements in both tissue fractions [6,[11][12][13].…”

Section: Tissue Preparationmentioning

confidence: 99%

Fatty acid composition of phospholipids in epithelium and stroma of human benign prostatic hyperplasia

Weisser

Krieg

1998

Prostate

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5α-androstane-3β,17β-diol hydroxylating enzymes in stroma and epithelium of human benign prostatic hyperplasia (BPH)

Cited by 23 publications

References 19 publications

Kinetic Parameters of 5α-Reductase Activity in Stroma and Epithelium of Normal, Hyperplastic, and Carcinomatous Human Prostates*

Kinetic Parameters of 5α-Reductase Activity in Stroma and Epithelium of Normal, Hyperplastic, and Carcinomatous Human Prostates*

Die benigne Prostatahyperplasie - das Ergebnis einer altersbedingten Entgleisung der Androgen-Estrogen-Balance?

Fatty acid composition of phospholipids in epithelium and stroma of human benign prostatic hyperplasia

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