Synandrogenic and Antiandrogenic Effect of Progestins: Comparison with Nonprogestational Antiandrogens<sup>1</sup>

Mowszowicz, Irène; Brown-Bieber, Dale; Chung, Kyu‐Rhim; Bullock, Leslie P.; Bardin, C. Wayne

doi:10.1210/endo-95-6-1589

Cited by 129 publications

(39 citation statements)

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“…The mechanism by which RU 486 inhibits breast cell growth remains unclear since this compound was first de scribed as a progesterone antagonist in clini cal trials and, as such, proposed as a contragestive or chemical precocious abortifacient [29], However, the dual properties of anti hormones and especially antiestrogens are well known [27,30] and it seems probable that, like tamoxifen, RU 486 will have biphasic (agonistic and antagonistic) proper ties, depending on the presence of a pure progestin such as R 5020 in the medium. Indeed, when the culture medium is supple mented with an equimolar concentration or R 5020 and RU 486, it can be noted that cell growth inhibition decreases.…”

Section: Effects On Breast Cell Multiplicationmentioning

confidence: 99%

Antiestrogen Action of Progesterone in Breast Tissue

Mauvais-Jarvis¹,

Kuttenn²,

Gompel³

1987

Horm Res

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This review analyzes recent data from international literature concerning the antiestrogen action of progesterone and progestins at the level of mammary cells in culture from either breast cancer lines or normal breast obtained from reduction mammoplasties. Most data indicate that progesterone and progestins have a strong antiestrogen effect on breast cell appreciated by the decrease of estradiol receptor content, the decrease of cell multiplication and the stimulation of 17β-hydroxysteroid activity which may be considered as a marker of breast cell differentiation dependent of progesterone receptor.

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Section: Effects On Breast Cell Multiplicationmentioning

confidence: 99%

Antiestrogen Action of Progesterone in Breast Tissue

Mauvais-Jarvis¹,

Kuttenn²,

Gompel³

1987

Horm Res

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“…The most recently stud ied progestin, 6a-methylprogesterone (6MP). was found to have syn-, anti-and androgenic effects in normal female, but not Tfm/Y mice, which lack effective androgen receptors [6], These results were not unlike those we obtained with another androgenic progestin, medroxyprogesterone acetate (6a-methyl-17-acetoxy-4-pregnene-3.20-dione, MPA) [1]. i However, when the nuclear uptake of ?H-6MP in kidney and prostate-seminal vesicle was characterized, several unexpected results were obtained which suggested that 6MP was involved with more than just the androgen receptor in mouse kidney [6,7], In kidney, the nuclear retention of radioactivity follow ing 3H-6MP administration was relatively greater than for 3H-testosterone, while the converse was true for prostate-seminal vesi cle; the addition of several unlabelled ste roids enhanced rather than inhibited the nu clear uptake in kidney, but not in the pros tate-seminal vesicle complex; and finally, similar concentrations of radioactivity were retained by renal nuclei in normal female mice and in Tfm/Y mice, which lack effec tive androgen receptors [8], The ability of 6MP to increase RNA-polymerase activity in Tfm/Y mice suggested that this nuclear re tention was biologically effective [9], These data were evidence for the specific binding of 6MP to another steroid receptor in addition to the androgen receptor.…”

Section: Introductionmentioning

confidence: 52%

“…This frequent use and the subse quent side effects that have been reported have promoted interest in defining the spec trum of the biological effects manifested by these steroids. We have shown that a variety of progestins bind to the androgen receptor [3,4] and may simulate, inhibit or enhance androgen action [1,2,6,12], In our initial studies of the effects of 6MP on mouse kid ney, we found that 6MP stimulated andro genic responses such as kidney and prostateseminal vesicle growth and renal P-glucuronidase activity [6]. As predicted from these androgenic effects, 6MP was apparently bound by the androgen receptor as it com peted in vitro for 3H-testosterone binding in cytoplasm [3,4], However, the finding that in vivo 3H-6MP was retained in similar amounts by kidney nuclei from normal and Tfm/Y mice, which lack androgen receptors, was unexpected [7], This suggested that another receptor was also involved.…”

Section: Discussionmentioning

confidence: 99%

“…These divergent ef fects correlate with the binding of the steroid to appropriate receptors. We have investi gated a scries of related progestins and corre lated their androgenic, synandrogenic and Supported in pan by NIH Grant HD 17666. antiandrogcnic effects on mouse kidney [1,2] with their binding to the androgen receptor [3,4] and their induction of RNA-polymerase activity [5]. The most recently stud ied progestin, 6a-methylprogesterone (6MP).…”

Section: Introductionmentioning

confidence: 99%

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Receptor Binding of 6α-Methylprogesterone in Mouse Kidney

Houben¹,

Bullock²

1985

Horm Res

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6α-Methylprogesterone (6MP) is an androgenic progestin that binds to the androgen receptor. However, results from an in vivo study suggested that 6MP was also bound by a second receptor. In the present study, we found that 6MP was bound in kidney cytosol from adrenalectomized/ovariectomized female mice as well as Tfm/Y mice, which lack androgen receptors. 6MP was bound with high affinity (K_d = 1.2 × 10^-8M)by a binder that was present in 7-8 times greater concentration than the androgen receptor and had the specificity of a glucocorticoid receptor. 6MP was bound with similar specificity in liver cytosol. These data indicate that, despite its androgenic effects, 6MP binds primarily to a glucocorticoid receptor in mouse kidney.

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“…other organs (14). However The costs of publication of this article were defrayed in part by the payment of page charges from funds made available to support the research which is the subject of the article.…”

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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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Synandrogenic and Antiandrogenic Effect of Progestins: Comparison with Nonprogestational Antiandrogens¹

Cited by 129 publications

References 0 publications

Antiestrogen Action of Progesterone in Breast Tissue

Antiestrogen Action of Progesterone in Breast Tissue

Receptor Binding of 6α-Methylprogesterone in Mouse Kidney

9S binding protein for androgens and progesterone.

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Synandrogenic and Antiandrogenic Effect of Progestins: Comparison with Nonprogestational Antiandrogens1

Cited by 129 publications

References 0 publications

Antiestrogen Action of Progesterone in Breast Tissue

Antiestrogen Action of Progesterone in Breast Tissue

Receptor Binding of 6&alpha;-Methylprogesterone in Mouse Kidney

9S binding protein for androgens and progesterone.

Contact Info

Product

Resources

About

Synandrogenic and Antiandrogenic Effect of Progestins: Comparison with Nonprogestational Antiandrogens¹

Receptor Binding of 6α-Methylprogesterone in Mouse Kidney