ABSTRACT
In the framework of a study on nonsteroidal androgens, the authors previously observed that in perhydrohexestrol series, the (+/-)-[(cis-4 hydroxycyclohexyl)-4(trans-4 hydroxycyclohexyl)-hexane] or cis-trans perhydrohexestrol and especially the (+/-)-(3,4 bis (trans-4-oxocyclohexyl)-hexane) or trans-trans perhydrodiketone, there is no affinity for AR (androgen receptor of the prostate) but they bind with high and specific affinity to the testosterone binding sites on ABP (epididymal androgen-binding protein). In this work, we describe the preparation, the stereochemistry and biological activities of trans-trans and cis-trans perhydrohexestrols and of trans-trans perhydrodiketone as well as their corresponding enantiomers. Biologically the tests AR and ABP are negative for the trans-trans perhydrohexestrol and of trans-trans perhydrodiketone and for its enantiomers. However for the enantiomers of cis-trans perhydrohexestrol and of trans-trans perhydrodiketone, the affinity of the (+) enantiomer for ABP is superior to that of the racemic and that of the (-) enantiomer, whereas the affinity for AR are zero. Chemically, the stereochemistry of the three racemics has been established by X-ray crystallographic analysis or by 1H n.m.r. The n.m.r. spectra have been analyzed in terms of chemical shifts and coupling constants.
Subject(s)
Androgen-Binding Protein/metabolism , Carrier Proteins/metabolism , Hexestrol/analogs & derivatives , Animals , Binding Sites , Crystallization , Epididymis/metabolism , Hexestrol/metabolism , Magnetic Resonance Spectroscopy , Male , Prostate/metabolism , Rats , Rats, Inbred Strains , Stereoisomerism , X-RaysSubject(s)
Prostaglandins/physiology , Animals , Anti-Inflammatory Agents/pharmacology , Aspirin/pharmacology , Chemical Phenomena , Chemistry , Kidney/metabolism , Nutritional Physiological Phenomena , Platelet Aggregation/drug effects , Prostaglandin Antagonists/pharmacology , Prostaglandins/biosynthesisSubject(s)
Androgen-Binding Protein/metabolism , Carrier Proteins/metabolism , Cyclohexanes/metabolism , Receptors, Androgen/metabolism , Receptors, Steroid/metabolism , Animals , Binding, Competitive , Cyclohexanols/metabolism , Cyclohexanones/metabolism , Cytosol/metabolism , Dihydrotestosterone/metabolism , Epididymis/metabolism , Estrenes/metabolism , Kinetics , Male , Metribolone , Prostate/metabolism , RatsABSTRACT
In order to study the role of lipids in the calcification process of the bone tissue, lipids have been extracted from undecalcified compact bone of calves less than 6 months old and from cows or oxen more than 2 years of age. Lipids from each group have been fractionned in "polar" and "non polar" types. Each type of lipid was shown to promote the formation of calcium phosphate precipitates in vitro. But only the polar lipids from calves bone promoted the formation of crystallised calcium phosphates, similar to hydroxyapatite. The identification of both crystallised and amorphous precipitates has been achieved by X-ray diffraction and chemical analysis.
Subject(s)
Bone and Bones/physiology , Calcification, Physiologic , Lipids/isolation & purification , Age Factors , Animals , Calcium Phosphates/metabolism , Cattle , Crystallization , Female , Hydroxyapatites/analysis , In Vitro Techniques , Lipid Metabolism , Male , Phospholipids/metabolism , X-Ray DiffractionABSTRACT
Contrary to the opinion generally expressed, decalcification of compact bone by EDTA does not allow a valid extraction of bone lipids due to the fact that they pass partly into the aqueous solution of EDTA, from which they are not entirely recoverable. Moreover, the loss of lipids is much more important when treatment with EDTA is applied directly to the bone powder, that is to say before a preliminary extraction by organic solvents. The percentages of loss in the EDTA solutions change according to the nature of the lipids and also according to the age of subjects. The so-called "liberation " of the bone lipids by EDTA could depend upon a mechanism entirely independent from the calcium chelation, perhaps through simple denaturation of the lipoproteins.
