DHT our friend??

[MisterX]

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Endocrinology 1990 Feb;126(2):1165-72 (ISSN: 0013-7227)

Grino PB; Griffin JE; Wilson JD [Find other articles with these Authors]
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235-8857.

Testosterone and dihydrotestosterone are believed to exert their androgenic effects by interacting with a single intracellular receptor protein in androgen target tissues. During fetal life, however, testosterone mediates the virilization of the Wolffian ducts into the epididymis, vas deferens, and seminal vesicles, whereas the urogenital sinus and external genitalia require the in situ conversion of testosterone to dihydrotestosterone to undergo male development. The reason why the signal provided by testosterone needs to be amplified in some androgen target tissues but not in others remains an enigma. To provide insight into the different actions of these androgens we studied their interaction with the human androgen receptor in fibroblasts cultured from the genital skin of a patient with 5 alpha-reductase deficiency. Dihydrotestosterone was formed in negligible amounts in these cells, and in some experiments the residual 5 alpha-reductase activity was further blocked with the 5 alpha-reductase inhibitor finasteride. Saturation analysis in fibroblast monolayers disclosed similar amounts of binding with testosterone and dihydrotestosterone, and the affinity of binding of dihydrotestosterone was, on the average, about 2-fold greater than that of testosterone. [3H]Testosterone also exhibited a 5-fold faster dissociation rate from the receptor than [3H]dihydrotestosterone. In thermolability experiments the [3H]testosterone-receptor complex displayed marked instability at 42 C with 2 nM [3H] testosterone, whereas with 20 nM [3H]testosterone, receptor stability was similar to that seen with [3H]dihydrotestosterone. In up-regulation experiments, 2 nM [3H]testosterone produced a 34% increase in specific androgen receptor binding after 24 h, whereas 20 nM [3H]testosterone produced an average increase of 64%. Our results suggest that the weaker androgenic potency of testosterone compared to that of dihydrotestosterone resides in its weaker interaction with the androgen receptor, most clearly demonstrable as an increase in the dissociation rate of testosterone from the receptor. When present in relatively high concentrations, however, testosterone overcomes this defect by mass action.(ABSTRACT TRUNCATED AT 400 WORDS).

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Credat Judaeus Apella, non ego. -

Horace's Satires, book 1, satire 5, lines 100-101

[This message was edited by MisterX on 02-17-2002 at 06:22 AM.]

[MisterX]

Evidence for autosomal dominant inheritance of prostate cancer.

Am J Hum Genet 1998 Jun;62(6):1425-38 (ISSN: 0002-9297)

Schaid DJ; McDonnell SK; Blute ML; Thibodeau SN [Find other articles with these Authors]
Department of Health Sciences Research, Mayo Clinic/Mayo Foundation, Rochester, MN 55905, USA. schaid@mayo.edu.

A family-history cancer survey was conducted on 5,486 men who underwent a radical prostatectomy, for clinically localized prostate cancer, in the Department of Urology at the Mayo Clinic during 1966-95; 4,288 men responded to the survey. Complex segregation analysis was performed to assess the genetic basis of age at diagnosis and the familial clustering of prostate cancer. For the total group, no single-gene model of inheritance clearly explained familial clustering of disease, which could be partly explained by lack of Hardy-Weinberg equilibrium, with an excess of homozygotes. After accounting for deviations from Hardy-Weinberg equilibrium, the best-fitting model that explained the familial aggregation and age at diagnosis was a rare autosomal dominant susceptibility gene, and this model fitted best when probands were diagnosed at <60 years of age. The model predicts that the frequency of the susceptibility gene in the population is .006 and that the risk of prostate cancer by age 85 years is 89% among carriers of the gene and 3% among noncarriers. A strength of our study is its large size, such that genetic models could be fitted within strata defined by the age of the proband. Although the autosomal dominant model was consistently the best model, the parameter estimates differed somewhat (P=.03) across the different age groups, suggesting genetic heterogeneity. Additional evidence that the hereditary basis of prostate cancer is likely to be genetically complex was provided by the following: (1) there was a significantly elevated age-adjusted risk of prostate cancer among brothers of probands, compared with their fathers (relative risk 1.5 [95% confidence interval 1.4-1.7]); (2) the autosomal dominant model predicted an excess of homozygotes, over that predicted by Hardy-Weinberg equilibrium; and (3) the model-predicted risk of prostate cancer among relatives was inadequate when probands were diagnosed at age >=70 years.

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Credat Judaeus Apella, non ego. -

Horace's Satires, book 1, satire 5, lines 100-101

[This message was edited by MisterX on 02-17-2002 at 06:23 AM.]

[MisterX]

Hoffman MA, DeWolf WC, Morgentaler A.

Division of Urology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.

PURPOSE: The association of free and total testosterone with prostate cancer is incompletely understood. We investigated the relationship of serum free and total testosterone to the clinical and pathological characteristics of prostate cancer. MATERIALS AND METHODS: We retrospectively reviewed the clinical records of 117 consecutive patients treated by 1 physician and diagnosed with prostate cancer at our medical center between 1994 and 1997. Low free and total testosterone levels were defined as 1.5 or less and 300 ng./dl., respectively. RESULTS: After evaluating all 117 patients we noted no correlation of free and total testosterone with prostate specific antigen, patient age, prostatic volume, percent of positive biopsies, biopsy Gleason score or clinical stage. However, in patients with low versus normal free testosterone there were an increased mean percent of biopsies that showed cancer (43% versus 22%, p = 0.013) and an increased incidence of a biopsy Gleason score of 8 or greater (7 of 64 versus 0 of 48, p = 0.025). Of the 117 patients 57 underwent radical retropubic prostatectomy. In those with low versus normal free testosterone an increased mean percent of biopsies demonstrated cancer (47% versus 28%, p = 0.018). Pathological evaluation revealed stage pT2ab, pT2c, pT3 and pT4 disease, respectively, in 31%, 64%, 8% and 0% of patients with low and in 40%, 40.6%, 12.5% and 6.2% in those with normal free testosterone (p>0.05). CONCLUSIONS: In our study patients with prostate cancer and low free testosterone had more extensive disease. In addition, all men with a biopsy Gleason score of 8 or greater had low serum free testosterone. This finding suggests that low serum free testosterone may be a marker for more aggressive disease.

PMID: 10687985 [PubMed - indexed for MEDLINE]
Drugs Aging 1999 Aug;15(2):131-42 Related Articles, Books, LinkOut


LOW TEST LEVELS NOT HIGH


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Credat Judaeus Apella, non ego. -

Horace's Satires, book 1, satire 5, lines 100-101

[This message was edited by MisterX on 02-17-2002 at 06:24 AM.]

[MisterX]

I hijacked most of the above 7 or so from other sites and posts to compile any other info that could be useful. I hope this helps to those who are interested in prostate health, with AAS and HRT. Take care.


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Credat Judaeus Apella, non ego. -

Horace's Satires, book 1, satire 5, lines 100-101