Binding of Pregnenolone and Progesterone by Prostatic “Receptor” Proteins

Karsznia, R; Wyss, R; Heinrichs, Wm. LeRoy; Herrmann, Walter

doi:10.1210/endo-84-5-1238

Cited by 26 publications

(3 citation statements)

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“…Although these effects may well be mediated through androgen receptors directly (Bullock, Barthe, Mowszowicz, Orth & Bardin, 1975) or after metabolism of progesterone to androgens, the intervention of a progesterone-binding protein, such as that observed by Karsznia, Wyss, Heinrichs & Herrmann (1969), must be considered. Other progestogens have anti-androgenic effects ; for example, cyproterone acetate causes regressive changes in the epithelial cells of rat prostate similar to those seen after castration (Dahl & Tveter, 1974;Loving & Flickinger, 1976).…”

Section: Discussionmentioning

confidence: 99%

Binding of Methyltrienolone (R1881) to a Progesterone Receptor-Like Component of Human Prostatic Cytosol

Cowan¹,

Cowan²,

Grant³

1977

Journal of Endocrinology

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The synthetic steroid methyltrienolone (R1881, 17beta-hydroxy-17alpha-methyl-estra-4,9,11-trien-3-one) binds with high affinity to protein in cytosols prepared from human hyperplastic prostate. R1881 also binds to the androgen receptor of rat prostate and the progesterone receptor of rabbit uterus. Other steroids compete with R1881 for unoccupied binding sites in the human prostatic cytosols in a manner similar to that observed with the rabbit uterine progesterone receptor, rather than the rat prostatic androgen receptor. The progesterone receptor-like binding sites are a feature of the prostatic stroma rather than the epithelium.

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Section: Discussionmentioning

confidence: 99%

Binding of Methyltrienolone (R1881) to a Progesterone Receptor-Like Component of Human Prostatic Cytosol

Cowan¹,

Cowan²,

Grant³

1977

Journal of Endocrinology

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“…Steroid-binding proteins had previously been isolated from the prostate by other groups. As early as 1969, Karsznia et al [42] reported the presence of steroid-binding receptor proteins in the prostate. As work progressed, it was recognized [37] that several other workers [36,43] had independently isolated and characterized a protein apparently identical with EBP and that human prostate likewise contained an immunochemically similar component [38].…”

Section: Control Of Androgen-insensitive Cellsmentioning

confidence: 99%

Approaches to prostatic cancer chemotherapy using the dunning R3327H prostatic adenocarcinoma

et al. 1985

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Androgen-responsive cells: To determine if testosterone or dihydrotestosterone is the main trophic hormone of prostatic adenocarcinoma, we have treated Dunning R3327H prostatic adenocarcinoma-bearing rats with 6-methylene progesterone, which blocks conversion of testosterone to dihydrotestosterone. Copenhagen-Fisher rats were treated with steroid (20 mg/Kg daily) immediately following implantation of tumor and thereafter for 117 days. There was a 92% inhibition of growth of tumors and a lesser effect upon prostate and seminal vesicles. Tumor-free body weights remained unchanged. Both treated and untreated tumors had equivalent DNA content on a per weight basis. This result supports the thesis that prostatic adenocarcinoma requires dihydrotestosterone for growth. Androgen-insensitive cells: Advanced prostate cancer does not respond to endocrine therapy but is temporarily controlled by the cytotoxic steroid estramustine. The latter shows significant selective binding to prostatic protein. To develop chemotherapeutic agents that will control androgen-insensitive cells and possess improved selectivity for prostatic protein, we have studied a number of steroids for their ability to displace 3H-labeled estramustine from prostatic cytosolic proteins. Surprisingly, a carbamido substituent at the C17 position was found to confer significant binding affinity for prostatic estramustine-binding protein. Extension of this structural characteristic to the estramustine type of molecule is being studied.

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“…However, it is uncertain whether progesterone has any hormonal function in androgen-dependent organs. A high-affinity binding protein for progesterone has been reported in rat testis (12) and prostate (13), and synandrogenic actions of progestins and testosterone have been described in Biochemistry: Wilson et al.…”

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confidence: 99%

9S binding protein for androgens and progesterone.

Wilson¹,

Lea²,

French³

1977

Proc. Natl. Acad. Sci. U.S.A.

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A steroid binding protein fraction with a sedimentation coefficient of approximately 9 S (molecular weight -200,000) has been identified in 105,000 X g supernatants of several androgen-responsive organs. Highest concentrations were found in epididymis and testis, but small amounts were detected in prostate, seminal vesicle, kidney, submandibular gland, and lung. The 9S protein binds [3H~dihydrotestosterone (17B-hydroxy-5a-androstan-3-one) and [3H~progesterone (4-pregnene-3,20-dione) with equilibrium binding constants of approximately 105 M-' and 106 M-1, respectively. The concentration of 9S binding sites in epididymis is approximately 10-11 mol/mg of supernatant protein, which is at least 105 times greater than the concentration of androgen receptor. 9S binding protein appears to be a nonsecretory, intracellular protein and has properties different from the androgen receptor. It is unretarded on DEAE-Sephadex chromatography at pH 8.0, and its sedimentation rate on sucrose gradients is not altered at high ionic strength (0.4 M KCI). Like the androgen receptor, its binding activity, which is maximal between pH 7 and 9.5, is heat labile, decreased by sulfhydryl reagents, and enhanced by 2-mercaptoethanol. It is suggested that because of its high concentration and low affinity, 9S binding protein may function in the intracellular accumulation or compartmentalization of androgens or progesterone.Androgen-dependent organs accumulate androgens from blood against a concentration gradient. This ability has been explained in part by the presence of high-affinity receptor proteins, which specifically bind and translocate androgen to the cell nucleus (1-5). Because of the small number of receptors in these target cells, however, it is unlikely that binding to this protein alone can fully account for their androgen accumulating capacity. Moreover, saturation of receptor sites with unlabeled androgen does not appreciably diminish target tissue accumulation of radioactive androgen (5). For these reasons it seems that additional mechanisms take part in promoting androgen accumulation, possibly membrane-associated active uptake or binding to high-capacity intracellular proteins. Experiments described in this report demonstrate the presence of a 9S protein fraction with a high binding capacity for dihydrotestosterone (1713-hydroxy-5a-androstan-3-one) and progesterone (4-pregnene-3,20-dione Preparation of 105,000 X g Supernatants. Supernatants (105,000 X g) were prepared as described (6) from tissues derived from Sprague-Dawley rats that were either castrated 24-48 hr before they were killed or hypophysectomized (Hormone Assay Lab, Chicago, IL) at age 60 days, 30 days before they were killed. Rats were killed by decapitation; the tissues were excised and placed in saline (40), blotted, and weighed. Tissues were minced and homogenized with a Thomas glass-Teflon homogenizer (decapsulated testes) or with an Ultra Turrax (other tissues) in three or four volumes of buffer containing 10% (wt/vol) glycerol/i mM EDTA/1 mM 2-mer...

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Binding of Pregnenolone and Progesterone by Prostatic “Receptor” Proteins

Cited by 26 publications

References 0 publications

Binding of Methyltrienolone (R1881) to a Progesterone Receptor-Like Component of Human Prostatic Cytosol

Binding of Methyltrienolone (R1881) to a Progesterone Receptor-Like Component of Human Prostatic Cytosol

Approaches to prostatic cancer chemotherapy using the dunning R3327H prostatic adenocarcinoma

9S binding protein for androgens and progesterone.

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