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SUMMARY
The stimulation in vitro of prostatic RNA polymerase activity by prostatic 5α-dihydrotestosterone—receptor complexes has been previously reported. Further investigations into the nature of the stimulation have now been carried out. By use of the selective inhibitor, α-amanitin, and by varying the concentration of ammonium sulphate in the assay media, both the nucleolar and extranucleolar forms of RNA polymerase could be stimulated, depending upon the ionic conditions employed. High ionic strength inhibited stimulation, either by interference with the association between steroid—receptor complexes and chromatin components, or by blocking the conversion of cytoplasmic complexes to a more 'active' form of the complex. 5α-Dihydrotestosterone—receptor complexes appeared to affect the template availability of prostatic chromatin, possibly in a way similar to that of the chromatin-associated proteins.
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SUMMARY
A method has been developed which allows the estimation of occupied and unoccupied androgen receptor sites in both cytoplasmic and nuclear fractions of rat ventral prostate. The procedure involves precipitation of receptor proteins and incubation of precipitates with labelled 5α-dihydrotestosterone. Uptake of 3H-labelled steroid at 0–4 °C gives an indication of free receptor, whereas binding at a raised temperature (15 °C) allows estimation of occupied receptor. Non-specific binding was measured in the presence of a 100-fold excess of unlabelled 5α-dihydrotestosterone. The exchange method was specific for androgens, and specific binding was detected only in fractions of androgen-dependent tissues. The method can be applied to cytosol, whole nuclei, chromatin and salt-extractable and salt-resistant protein preparations from nuclear fractions, and gives a reliable estimate of total receptor sites when occupied as compared with control measurements of unoccupied sites.
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Department of Neurology, Hadassah University Hospital, Jerusalem, Israel
(Received 27 October 1975)
Several criteria have been established for those proteins of fundamental importance in the mechanism of steroid hormone action as opposed to those, essentially transport proteins, which are unable to elicit a biological effect when associated with steroid. Receptor proteins found in target cells may be characterized by their restricted concentration but high affinity for steroid, together with high ligand and tissue specificity (Baulieu, Raynaud & Milgrom, 1970). In studies designed to show the organ specificity of the receptor for oestradiol in mammary tumours induced by 7,12-dimethylbenz [a] anthracene in the female rat (Powell-Jones, Jenner, Blarney, Davies & Griffiths, 1975), the presence in liver cytosol fractions of protein components specifically retaining oestradiol with high affinity but low capacity was demonstrated.
Fig. 1. Cytosols were prepared from liver tissue of a mammary tumour-bearing rat (cytosol protein 17 mg/ml) and from
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Tenovus Institute for Cancer Research, Welsh National School of Medicine, Heath Park, Cardiff, CF4 4XX
(Received 4 April 1975)
Compounds having antioestrogenic properties are potentially useful for the treatment of certain patients with metastatic cancer of the breast. This report describes studies on the ability of various potential antioestrogens, in particular two nitrogen-mustard-containing substances, ICI 79792 (1-{4-β-[bis(2-chloroethyl)amino]ethoxyphenyl}-trans diphenylbut-1-ene hydrochloride) and ICI 85966 (3,4-bis{p-[(N-bis-2-chloroethyl)carbamoyl]phenyl}hex-3-ene), to prevent the uptake of [3 H] oestradiol into rat mammary tumour nuclei in vitro.
Mammary tumours were induced in virgin female Sprague–Dawley rats by intubation of 7,12-dimethyibenz(a)anthracene (20 mg in 1 ml sesame oil). Tumours suitable for experimentation (2×2 cm) developed 7–12 weeks after intubation. Tumours were dissected free of connective tissue and obvious necrotic areas and minced with scissors. Equal weights of mince (1 g) were incubated (15 min at 30 °C) in Eagle's basal medium (10 ml/g tissue) supplemented with [2,4,6,7-3H] oestradiol (0·5 nmol/l,
