Sociedad Septiembre 11, 2014

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We performed a study of middle-aged men with type 2 diabetes to determine the interrelation of micturition disorders with deficiency of serum testosterone, in respect that the pathophysiology of prostatic hyperplasia is regarded as dysmetabolic dyshormonal state. The prospective study examined 112 men with type 2 diabetes randomized by the level of total testosterone. Lower urinary tract symptoms were assessed by I-PSS questionnaire. The study of serum total PSA, uroflowmetry, transrectal prostate ultrasonography were performed. testosterone.

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The activity of CYP3A was studied by measuring the rate of testosterone 6β-hydroxylation in liver microsomes. testosterone.

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Government-imposed restrictions did not influence long-term prescribing of testosterone to older men. By 2012, approximately 1 in every 90 men aged 66 or older was being treated with TRT, most with topical formulations. testosterone.

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CYP154C5 from Nocardia farcinica is a bacterial cytochrome P450 monooxygenase active on steroid molecules. The enzyme has recently been shown to exhibit exclusive regioselectivity and stereoselectivity in the conversion of various pregnans and androstans, yielding 16α-hydroxylated steroid products. This makes the enzyme an attractive candidate for industrial application in steroid hormone synthesis. Here, crystal structures of CYP154C5 in complex with four different steroid molecules were solved at resolutions of up to 1.9 Å. These are the first reported P450 structures from the CYP154 family in complex with a substrate. The active site of CYP154C5 forms a flattened hydrophobic channel with two opposing polar regions, perfectly resembling the size and polarity distribution of the steroids and thus resulting in highly specific steroid binding with Kd values in the range 10-100 nM. Key enzyme-substrate interactions were identified that accounted for the exclusive regioselectivity and stereoselectivity of the enzyme. Additionally, comparison of the four CYP154C5-steroid structures revealed distinct structural differences, explaining the observed variations in kinetic data obtained for this P450 with the steroids pregnenolone, dehydroepiandrosterone, progesterone, androstenedione, testosterone and nandrolone. This will facilitate the generation of variants with improved activity or altered selectivity in the future by means of protein engineering. testosterone.

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Comamonas testosteroni (C. testosteroni) is able to catabolize a variety of steroids and polycyclic aromatic hydrocarbons. 3,17β-Hydroxysteroid dehydrogenase (3,17β-HSD) from C. testosteroni is a key enzyme in steroid degradation. Understanding the mechanism of 3,17β-HSD gene (βhsd) induction may help us to elucidate its complete molecular regulation. Sequencing the C. testosteroni ATCC11996 genome lead us to identify the tetR (522 bp) downstream of βhsd. Two repeat sequences (RS; 13 bp), that are separated to each other by 1661 bp, were found upstream of βhsd. A bioinformatic analysis revealed that TetR family proteins act as transcriptional repressors which are sensitive to environmental signals. Since, C. testosteroni responds to environmental steroid induction and upregulates steroid catabolic genes, we hypothesized that TetR might act in C. testosteroni as repressor for βhsd expression. The tetR was cloned into different plasmids, including an EGFP reporter system, for functional characterization and/or overexpression. The data indicate that, indeed, TetR acts as a repressor for 3,17β-HSD expression. Testosterone in turn, which is known to induce βhsd expression, could not resolve TetR repression. To further substantiate TetR as repressor for βhsd expression, a tetR gene knock-out mutant of C. testosteroni was generated. TetR gene knock-out mutants showed the same basal low level of βhsd expression as the C. testosteroni wild type cells. Interestingly, testosterone induction leads to a strong increase in βhsd expression, especially in the tetR gene knock-out mutants. The result with the knock-out mutant, in principle, supports our hypothesis that TetR is a repressor for βhsd expression, but the exact role of testosterone in this context remains unknown. Finally, it turned out that TetR is obviously also involved in the regulation of the hsdA gene. testosterone.

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Although no associations between TH and sperm parameters were observed, present data support a positive effect of TH on SV size and a permissive role on the ejaculatory machinery, likely through an action on SV and epididymal contractility. This is the first study reporting such evidence. However, in contrast with the view that TH assessment is important for female fertility, our results do not support a systematic evaluation of thyroid function in males of infertile couples. How TH abnormalities impact male fertility needs to be addressed by further studies. testosterone.

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