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1. Analysis of Relation s Between Serum Levels of Epitestosterone, Estradiol, Testosterone, IGF -1 and Prostatic Specific Antigen in Men Benign Prostatic Hyperplasia and Carcinoma of the Prostate

Creator:
Hill, M., Bílek, R., Šafařík, L., and Stárka, l.
Type:
article, model:article, and TEXT
Subject:
Epitestosterone, Prostatic specific antigen, Insulin-like growth factor, Estradiol, Prostate, and Carcinoma
Language:
English
Rights:
http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public

2. How short-term transdermal treatment of men with 7-oxo-dehydroepiandrosterone influences thyroid function

Creator:
Hampl, R., Šulcová, J., Bílek, R., and Hill, M.
Type:
article, model:article, and TEXT
Subject:
7-oxo-dehydroepiandrosterone, Transdermal application, and Thyroid hormones
Language:
English
Description:
Dehydroepiandrosterone may influence thyroid function. Its metabolite, 7-oxo-dehydroepiandrosterone, a precursor of immunomodulatory 7-hydroxylated metabolites and thermogenic agent, belongs to candidates of steroid replacement therapy. The question was addressed whether its application does influence laboratory parameters of thyroid function. 7-Oxo-dehydroepiandrosterone in the form of emulgel, 25 mg/day, was applied transdermally to 21healthy men for 8 consecutive days. Morning blood was collected before the treatment (Day 0, Stage 1), during treatment (Day 5, Stage 2), on the first day after the last administration (Day 9, Stage 3), one week (Day 16, Stage 4), and 9 weeks (Day 72, Stage 5) after treatment termination. The levels of thyrotropin, free thyroxine and triiodothyronine, dehydroepiandrosterone, its sulfate and its 7-hydroxyepimers were measured. The changes were evaluated by analysis of variance and correlation analysis. During treatment a significant rise of 7β-hydroxy-dehydroepiandrosterone was observed, which persisted 1 week after treatment termination. No changes were observed in dehydroepiandrosterone and its sulfate. Though a slight but significant rise of TSH and of both thyroid hormones occurred during treatment, its levels soon returned to the basal values. It was concluded that treatment of 7-oxo- dehydroepiandrosterone affects the thyroid parameters only temporarily and that it provides a considerable persistent amount of 7β-hydroxy-dehydroepiandrosterone.
Rights:
http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public

3. The computer modelling of human TRH receptor, TRH and TRH-like peptides

Creator:
Bílek, R. and Stárka, L.
Type:
article, model:article, and TEXT
Subject:
Throtropin-releasing hormone receptor, TRH, TRH-like peptides, and Computer modeling
Language:
English
Description:
The aim of this work was to verify the possibility of interactions between the human TRH receptor (an integral membrane protein which belongs to family 1 of G-protein coupled receptors) and TRH-like peptides presented in the prostate gland. These peptides are char acterized by substitution of basic amino acid histidine (related to authentic TRH) for neutral or acidic amino acid, such as glutamic acid, phenylalanine, glutamine or tyrosine. The physiological function of TRH-like peptides in peripheral tissues is not precisely known. However, according to our recent experiments, we assume the existence of a local hormona l network formed by TRH-like peptides and TSH in the prostate gland. The network can be associated with circulating thyroid and steroid hormones, and may represent a new regulatory mechanism influencing the proliferative ability of prostatic tissue. A similar network of authentic TRH and TSH was already found in the gastrointestinal tract. The experimentally determined 3D-structures of human TRH receptor (hTRHr) and TRH-like peptides are not available. From this point of view we used de novo modeling procedures of G-protein coupled receptors on an automated protein modeling server used at the Glaxo Wellcome Experimental Research (Geneva, Switzerland). 3D-s tructures of TRH-like peptides were determined with a computer program CORINA (written by the team of J. Gasteiger, Computer-Chemie-Centrum and Institute for Organic Chemistry, University of Erlangen-Nurenberg, Germany). The generated PDB files with 3D-coordinates were visualized with Swiss-Pdb Viewer Release 3.51 (Glaxo Wellcome). From recent results it is evident that polar amino acids belonging to the extracellular terminus of hTRHr transmembrane regions can participate in interactions between TRH and hTRHr. There is no direct evidence that TRH-like peptides interact with the presented hTRHr model. On the contrary, with respect to the similar 3D-shape and the identity of terminal amino acids, it appears that these interactions are highly probable as well as the nearly 100 % cross-reactions between TRH or TRH-like peptides and antibody specific against authentic TRH. Closed terminal amino acids (pyroglutamic acid and proline-amide) of TRH or TRH-like peptides are important for these interactions. Desamido-TRH or glutamyl metabolites will be repelled by the negative potential of ASP195 (E: D93) and GLU298 (G: E137).
Rights:
http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public