Search Results
You are looking at 1 - 4 of 4 items for
- Author: W. I. P. MAINWARING x
- Refine by access: All content x
Search for other papers by W. I. P. MAINWARING in
Google Scholar
PubMed
SUMMARY
A thermolabile protein with the properties of a steroid 'receptor' was identified in the cytoplasmic or 105,000 g supernatant fraction of the rat prostate. The receptor has a particular binding specificity towards 5αdihydrotestosterone. Testosterone is bound to a lesser extent but other steroids, including certain androgenic hormones, are not bound. The sedimentation coefficient of 8·0 s and the frictional ratio of 1·96, equivalent to a molecular weight of 2·74 × 105, clearly distinguish the soluble androgen-receptor from the androgen-binding globulin in serum and the androgen-receptor in the prostatic nucleus. Like the nuclear receptor, however, the soluble receptor is probably an acidic protein. Both cysteine and tryptophan residues appear necessary for maintaining the functional configuration of the receptor.
Search for other papers by W. I. P. MAINWARING in
Google Scholar
PubMed
SUMMARY
The specificity of the binding of [1,2-3H]testosterone to nuclei of various rat tissues in vivo has been studied. A significant amount of radioactivity was retained in the nuclei of androgen-dependent tissues only, particularly the ventral prostate gland. The bound radioactivity was only partially recovered as [1,2-3H]testosterone; the remainder was identified as [3H]5α-dihydrotestosterone. Efforts were made to characterize the binding component, or 'receptor', in prostatic nuclei. On digestion of nuclei labelled in vivo with [1,2-3H]testosterone, with enzymes of narrow substrate specificity, only trypsin released tritium, suggesting that the receptor is a protein. On the basis of subfractionation studies of labelled nuclei, the receptor is an acidic protein. The androgen—receptor complex could be effectively extracted from the prostatic nuclei in 1 m-NaCl and from the results of fractionations on a calibrated agarose column, the complex has a molecular weight 100,000–120,000. The specificity of the binding of steroids to such 1 m-NaCl extracts in vitro was investigated by the equilibrium dialysis procedure. Under these conditions, the specificity of the binding of [1,2-3H]testosterone demonstrated in vivo could not be simulated. The receptor is probably part of the chromatin complex but its precise intranuclear localization cannot be determined by biochemical procedures alone.
Search for other papers by W. I. P. MAINWARING in
Google Scholar
PubMed
Search for other papers by F. R. MANGAN in
Google Scholar
PubMed
SUMMARY
A search has been conducted for specific, 5α-dihydrotestosterone-binding proteins in a wide variety of tissues and cells upon which androgenic steroids have pronounced morphological and biochemical effects. High affinity binding proteins of this nature have been identified in cytoplasmic and nuclear extracts from a diversity of accessory sexual glands of many species, mouse kidney, testis and certain experimental androgen-dependent tumours. They are notably absent in most types of skeletal muscle and in soluble extracts prepared from prokaryotic organisms. The implications of these findings to the mechanism of action of androgenic steroids are discussed. While the selective binding of 5α-dihydrotestosterone indubitably plays a role of paramount importance in the mechanism of action of androgens in many accessory sexual glands throughout life, this process may be of importance in other tissues only during the period of early growth and development. A severe limitation to the importance of the binding of 5α-dihydrotestosterone in certain adult tissues is imposed by the very low activity of the enzyme, 5α-reductase, responsible for the formation of 5α-dihydrotestosterone.
Search for other papers by W. I. P. MAINWARING in
Google Scholar
PubMed
Search for other papers by E. J. G. MILROY in
Google Scholar
PubMed
SUMMARY
A search has been conducted for specific androgen-binding proteins in soluble extracts of normal human prostate tissue and in surgical samples removed at retropubic prostatectomy for benign prostatic hyperplasia. Proteins with a particularly high affinity for a metabolite of testosterone, 5α-dihydrotestosterone, have been identified in studies on the binding of 3H-labelled steroids in vitro. The 5α-dihydrotestosterone-protein complexes have been partially characterized using sucrose density gradient centrifugation and gel-exclusion chromatography. The androgen receptors in the human prostate gland are remarkably similar to those previously described in the accessory sexual glands of experimental animals. These findings have been confirmed by the analysis of extracts of hyperplastic prostate glands labelled by the administration of [3H]testosterone in vivo. No attempt was made to correlate the degree of binding with the histological appearance of the specimens of hyperplastic prostate or to determine whether the receptors were principally present in the hyperplastic nodules. Such androgen-binding proteins were not present in serum, skeletal muscle or adipose tissue. The possible relevance of these findings to the onset of clinical disorders in the human prostate gland is briefly discussed.
