C.B. Smith
Hammersmith Hospital
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Featured researches published by C.B. Smith.
Molecular and Cellular Endocrinology | 1977
R. Ghanadian; C.B. Smith; G. D. Chisholm
An in vivo and in vitro study was carried out on the prostate from the female Praomys (Mastomys) natalensis to identify and characterize the binding of androgens within the cytoplasm. The labelled cytosol was prepared and subjected to gel exclusion chromatography and density gradient centrifugation. A macromolecular protein associated with the radioactivity was isolated on Sephadex G-200. Subsequent analysis of the steroid receptor complex showed that the major part of the radioactive steroid (64 percent) was dihydrotestosterone. This binding was inhibited by unlabelled testosterone and could not be demonstrated in liver cytosol. Characterization of this dihydrotestosterone receptor complex revealed a sedimentation coefficient of 4.6 s in the presence of a high salt solution (0.4 M KCl). The complex aggregated in the absence of 0.4 M KCl and sedimented preferentially from 5.6-7.4 s together with polydisperse aggregates of higher sedimentation coefficients. The use of this animal as an experimental model for hormonal studies on the prostate is suggested.
Molecular and Cellular Endocrinology | 1978
C.B. Smith; R. Ghanadian; G. D. Chisholm
Abstract The inhibitory effects of stilboestrol and representatives from three main classes of antiandrogens on the dihydrotestosterone receptor complex isolated from the nuclei of rat ventral prostate were compared. After labelling of the tissue in vivo or in vitro with [ 3 H]testosterone in the presence or absence of test drugs, the nuclear extracts were prepared and the inhibitory effect on the steroid-receptor complex was evaluated. Equimolar doses (1 μmol/100 g body weight) of cyproterone acetate, chlormadinone acetate, SC 9022 and flutamide inhibited the binding of dihydrotestosterone to the receptor complex by 48–54%, whereas in the in vitro studies an equimolar concentration (0.1 μM) inhibited the binding by 45–58% with the exception of flutamide which had no effect. Under these experimental conditions stilboestrol had no effect on the binding of dihydrotestosterone to the nuclear receptor.
Urological Research | 1977
R. Ghanadian; G. Auf; C.B. Smith; G.D. Chisholm; N.J. Blacklock
SummaryThe presence of an androgen receptor protein in the supernatant preparation of the prostate from Rhesus monkey (macaca mulatta) is described. The molecular weight of this receptor protein was found to be 2.8–2.9×105 daltons. The levels of free and bound androgen receptors were measured in the caudal and cranial lobes of the prostate by an exchange assay using methyltrienolone (R1881). The concentration of the free binding sites in the caudal lobe ranged between 3.7–23.7 fmol/mg protein. The value in the cranial lobe was 2.0–7.7 fmol/mg protein. The total binding sites in the caudal lobe ranged between 36.0–112.7 and in the cranial between 21.2–55.0 fmol/mg. The bound receptor ranged between 43.3–109.0 and 19.1–47.3 fmol/mg protein for caudal and cranial lobes respectively. The level of both bound and free receptors was found to be significantly higher in the caudal lobe. This data suggests that the two lobes of the prostate in the Rhesus monkey can be equated with the two zones of the human prostate in respect of androgen responsiveness.
Urological Research | 1984
Janet M. Allen; Gordon Williams; J. P. O'shea; C.B. Smith; T. Yeo; D. Kerle; Stephen R. Bloom
SummarySerum concentrations of gonadotropins, testosterone and dehydrotestosterone were determined in patients receiving conventional endocrine therapy for advanced metastatic adenocarcinoma of prostate. The effect over 4 h of a single dose of a long acting analogue of LHRH was determined in these patients and compared to the response in patients receiving the analogues as first choice of treatment. Oestrogen therapy was found to suppress basal and stimulated gonadotropins and testicular androgens. Cyproterone therapy only partially reduced basal hormone concentrations and the response to the LHRH analogue was delayed. Orchidectomy resulted in elevated gonadotropins and an exaggerated response to the analogue. As patients who relapse while failing conventional therapy, may subsequently be treated by further endocrine manipulation, precise determination of their endocrine status should predict any expected benefit. Patients previously treated with stilboestrol are unlikely to respond to orchidectomy or LHRH analogue.
Urological Research | 1978
C.B. Smith; R. Ghanadian; G. D. Chisholm
SummaryA steroid receptor protein was isolated from the cytoplasmic fraction of Mastomys prostate. Following in vivo and in vitro labelling of the tissue with tritiated testosterone or dihydrotestosterone, samples were analysed by gel exclusion chromatography or sucrose density gradient centrifugation. A steroid receptor complex was isolated on Sephadex G-200. Analysis of the steroids associated with this complex showed that the major part of the bound radioactivity was 5 α-dihydrotestosterone. The binding was inhibited by unlabelled testosterone and could not be demonstrated in the liver cytosol. Using sucrose desity gradient centrifugation, the dihydrotestosterone receptor complex sedimented at 5.6 s together with heavier aggregates. In the presence of 0.4 M KCl a single complex was sedimented at 4. 6 s. The results demonstrate a receptor protein in the cytosol of the Mastomys prostate which binds to dihydrotestosterone and is comparable to that of rat prostate.
BJUI | 1986
Gordon Williams; Kerle D; Ware H; A. Doble; Helen Dunlop; C.B. Smith; Janet M. Allen; T. Yeo; Stephen R. Bloom
BJUI | 1990
Gordon Williams; R. Asopa; P. D. Abel; C.B. Smith
BJUI | 1977
R. Ghanadian; C.B. Smith; G. D. Chisholm; N. J. Blacklock
BJUI | 1977
R. Ghanadian; C.B. Smith; Gordon Williams; G. D. Chisholm
Journal of Steroid Biochemistry | 1984
D. Kerle; H. Ware; C.B. Smith; T Yeo; Janet M. Allen; Stephen R. Bloom; G. Williams