Nuclear components responsible for the retention of steroid–receptor complexes, especially from the standpoint of the specifcity of hormonal responses

Mainwaring, W.I.P.; Symes, Elizabeth K.; Higgins, Stephen J.

doi:10.1042/bj1560129

Cited by 62 publications

(11 citation statements)

References 42 publications

(43 reference statements)

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“…Although proof of the participation of androgen receptors in the direct control of cell proliferation, 5a-reductase activity and secretory acid phosphatase activity is contingent on a fuller understanding of the interaction of androgen receptors with chromatin acceptor sites (Davies & Griffiths, 1973;Mainwaring et al, 1976;Rennie, 1979), the results obtained in the present investigation favour the hypothesis that androgen receptors, rather than non-receptor-bound nuclear androgen, modulate cell proliferation and 5a-reductase activity. Since the association constant (Ka) for the binding of dihydrotestosterone to chromatin-bound receptor sites is of the order of 5 x 107M-1 (Rennie, 1979), and since the nuclear concentration of receptor sites is far lower than the concentration of dihydrotestosterone, the most obvious function of the excess nuclear dihydrotestosterone is to ensure that all the receptor sites within the nucleus are occupied with androgen.…”

Section: Effects Of Dose On the Intracellular Concentration Of Dihydrsupporting

confidence: 70%

Radioimmunoassay measurements of nuclear dihydrotestosterone in rat prostate. Relationship to androgen receptors and androgen-regulated responses

Larminat¹,

Rennie²,

Bruchovsky³

1981

Biochemical Journal

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The concentration of dihydrotestosterone was measured by radioimmunoassay in nuclear and cytoplasmic extracts from rat ventral prostates. In the regenerating prostates of castrated rats treated with dihydrotestosterone for 4 days, the nuclear concentration of this steroid increased from approx. 70nM to 800nM as a linear function of the injected dose, whereas the cytoplasmic concentration remained relatively constant (70-130nM). Isotope-exchange measurements of nuclear androgen receptors by using [3H]methyltrienolone indicated that, although the concentration of nuclear dihydrotestosterone was several-fold higher than the concentration of androgen receptors, they were logarithmically related. The recruitment of prostatic cells into the growth fraction and the stimulation of 5 a-reductase activity were more directly correlated to the nuclear concentration of androgen receptors than to the total nuclear concentration of dihydrotestosterone. Maximal restoration of a specific isoenzyme of acid phosphatase was achieved when approx. 2000 androgen receptors were present in the prostatic nuclei; higher concentrations of nuclear androgen receptors were associated with decreased amounts of this enzyme. Hence the results imply, first, that the total amount of dihydrotestosterone accumulated by nuclei is not a direct consequence of carrier-mediated transport by androgen receptors, and, secondly, that, whereas acid phosphatase may be differentially controlled by androgens in the regenerating prostate, increases in the amount of cell proliferation and 5a-reductase activity directly parallel increases in the nuclear concentration of androgen receptors.In the prostate, androgenic regulation of physiological functions and cellular growth is attributed largely to the formation, and subsequent binding to chromatin, of androgen-receptor complexes (King & Mainwaring, 1974 (Coffey, 1974;Rennie et al., 1975;Van Doorn et al., 1976). Although it has been postulated that androgen receptors are involved in the uptake and retention of dihydrotestosterone by target-cell * To whom correspondence should be addressed.Vol. 200 nuclei (Rennie & Bruchovsky, 1973;Bruchovsky et al., 1975a), a direct stoicheiometric relationship has not been demonstrated. When castrated rats are injected with radioactive androgen in the ventral prostate the concentration of radioisotope measured in nuclei exceeds that measured in the cytoplasm (Bruchovsky et al., 1975b). However, the concentration of androgen-receptor complexes recovered from the nuclei is insufficient to account for the nuclear influx of androgens if a mole-to-mole relationship is assumed. Furthermore, radioimmunoassay measurements of dihydrotestosterone in ventral prostates from non-castrated rats have indicated that only about 20% of the endogenous nuclear androgen is bound to androgen receptors (Bruchovsky et al., 1980). Whether the large nuclear concentration of non-receptor-bound dihydrotestosterone is achieved through a receptor mechanism or

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Section: Effects Of Dose On the Intracellular Concentration Of Dihydrsupporting

confidence: 70%

Radioimmunoassay measurements of nuclear dihydrotestosterone in rat prostate. Relationship to androgen receptors and androgen-regulated responses

Larminat¹,

Rennie²,

Bruchovsky³

1981

Biochemical Journal

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“…Early characterization of the chromatin acceptor sites has been reported for the progesterone (P) [Spelsberg et al, 1983[Spelsberg et al, , 1984[Spelsberg et al, , 1987aPerry and Lopez, 1978;Lopez et al, 1985;Cobb and Leavitt, 19871, estrogen (E,) [Ruh et al, 1981;Ross and Ruh, 1984;Singh et al, 19841, and androgen [Mainwaring et al, 1976;Klyzsejko-Stefanowicz et al, 1976;Wang, 1978;Rennie et al, 19871 receptors in a variety of animal systems. Chromatin acceptor sites for the avian oviduct progesterone receptor (PR) have been studied extensively and found to consist of complexes of specific acceptor proteins tightly bound t o specific DNA sequences [Spelsberg et al, 1972[Spelsberg et al, , 1984[Spelsberg et al, , 1987a[Spelsberg et al, ,b, 1988Schuchard et al, 1991a,b;Pikler et al, 1976;Kon and Spelsberg, 1982;Hora et al, 1986;Goldberger et al, 1987;Goldberger and Spelsberg, 1988;Rejman et al, 19911.…”

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confidence: 96%

Immunohistochemical localization of the avian progesterone receptor and its candidate receptor binding factor (RBF‐1)

Zhuang

Landers

Schuchard

et al. 1993

J of Cellular Biochemistry

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An avian oviduct nuclear matrix protein in the 6-10 kDa size range has been implicated to function in the cell-free nuclear binding of the avian oviduct progesterone receptor (PR). This protein, termed the receptor binding factor-1 (RBF-1), has been purified and partially characterized [Schuchard et al.: Biochemistry 30:4535-4542, 1991]. This paper describes the immunohistochemical co-localization of the RBF-1 and PR in the avian oviduct cell nuclei and rat reproductive cell nuclei using antibodies directed specifically against the RBF-1 and activated PR. In the undifferentiated oviduct, the immunoreactivities for both PR and RBF-1 were co-localized in the nuclei of only epithelial cells, but not the stromal cells or smooth muscle cells. In the partially differentiated oviduct of estrogen treated chicks, the immunoreactivity co-localized in the nuclei of not only epithelial but also glandular and stromal cells. Staining for the PR, but not RBF-1, was detected in the smooth muscle cells. The intensity of the PR but not the RBF-1 staining was markedly down-regulated in these cells at 2 and 6 h after treatment of the animals with progesterone (P). However, the band patterns for RBF-1 in the Western blots did show qualitative changes which may reflect P-induced posttranslational modifications which alter the epitope on the RBF-1. Interestingly, immunohistochemical analysis of several reproductive tissues of the rat showed that certain cell types in the uterus, ovary, and prostate displayed strong positive nuclear staining for an RBF-1-like antigen(s).(ABSTRACT TRUNCATED AT 250 WORDS)

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“…This might be expected from theoretical considerations for rat kidney contains neither cytoplasmic androgen receptors (King <& Mainwaring, 1974) nor nuclear acceptors for a receptor-androgen complex (Mainwaring, Symes & Higgins, 1976). The androgen-dependent regulation of microsomal 3a-and 20/Î-HSDH activity must involve a mechanism other than the classical system comprising cytoplasmic receptor and nuclear acceptor.…”

Section: Discussionmentioning

confidence: 96%

ENDOCRINE REGULATION OF SEX-DEPENDENT HYDROXYSTEROID DEHYDROGENASE ACTIVITIES IN RAT KIDNEY: NADP-DEPENDENT MICROSOMAL 3α- AND 20β-Hydroxysteroid DEHYDROGENASE

Ghraf¹,

Lax²,

Wagner³

et al. 1977

Journal of Endocrinology

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The NADP-dependent microsomal kidney enzymes, 3alpha- and 20beta-hydroxysteroid dehydrogenase (HSDH), which exhibit considerable sex differences in their activities (male:female activity ratios, 16:1 and 30:1 respectively), were investigated after interference with the pituitary-gonad and pituitary-adrenal systems. Prepubertal gonadectomy as well as hypophysectomy of mature male rats led to a decline in HSDH activity to almost that found in the normal female rat, whereas activities in female rats were unaffected. Testosterone induced typical male 3alpha-HSDH activity in both gonadectomized and hypophysectomized rats of either sex. Administration of 5alpha-dihydrotestosterone (5alpha-DHT) or 5alpha-androstane-3alpha, 17beta-diol to hypophysectomized male rats was equally effective in restoring full 3alpha- and 20beta-HSDH activities whereas 5alpha-androstane-3beta, 17beta-diol was less effective and dehydroepiandrosterone was ineffective. Simultaneous administration of cyproterone acetate did not block the inductive action of 5alpha-DHT. Administration of chorionic gonadotrophin, pregnant mare serum gonadotrophin or a combination of luteinizing hormone and follicle-stimulating hormone to hypophysectomized male rats all led to parallel increases in the weight of the seminal vesicles and in both renal enzyme activities; administration of growth hormone, prolactin or thyroid-stimulating hormone was ineffective. Adrenalectomy of gonadectomized, but not of hypophysectomized male rats, caused a further drop in activity to the normal female level. Adrenalectomy of otherwise intact rats did not affect either enzyme activity. The hypophysis was involved in the regulation of the two NADP-dependent renal HSDH activities through its gonadotrophic function in male rats; adrenal secretions were of little physiological significance.

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Nuclear components responsible for the retention of steroid–receptor complexes, especially from the standpoint of the specifcity of hormonal responses

Cited by 62 publications

References 42 publications

Radioimmunoassay measurements of nuclear dihydrotestosterone in rat prostate. Relationship to androgen receptors and androgen-regulated responses

Radioimmunoassay measurements of nuclear dihydrotestosterone in rat prostate. Relationship to androgen receptors and androgen-regulated responses

Immunohistochemical localization of the avian progesterone receptor and its candidate receptor binding factor (RBF‐1)

ENDOCRINE REGULATION OF SEX-DEPENDENT HYDROXYSTEROID DEHYDROGENASE ACTIVITIES IN RAT KIDNEY: NADP-DEPENDENT MICROSOMAL 3α- AND 20β-Hydroxysteroid DEHYDROGENASE

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