16-alpha-ethyl-21-hydroxy-19-nor-4-pregnene-3-20-dione and Prostatic-Hyperplasia

In rat uterus and prostate, 7 alpha, 17 alpha-dimethyl-19-nortestosterone (DMNT) binds to the androgen receptor specifically and with high affinity. However, this steroid does not bind to glucocorticoid receptors, since it does not displace binding of [3H]triamcinolone acetonide in calf thymus cytosol. In calf uterine and human breast tumor cytosols DMNT binds to the androgen and progesterone receptors, since binding of [3H] DMNT is displaced by unlabeled 16 alpha-ethyl-21-hydroxy-19-nor-4-pregnene-3, 20-dione triamcinolone acetonide, and 5 alpha-dihydrotestosterone (DHT). Conversely, binding of [3H]16 alpha-ethyl-21-hydroxy-19-nor-4-pregnene-3,20-dione is effectively competed for by unlabeled DMNT but not by DHT. The observed differences in binding of [3H]DMNT to rat and calf uterine cytosols suggest the species specificity of progesterone receptors. Unlike DHT, DMNT has no appreciable binding to human sex-steroid binding globulin. These findings suggest DMNT as a suitable ligand for measurement and characterization of androgen receptors in rat and human prostate.

Topics: Animals; Blood Proteins; Breast; Cattle; Cell Nucleus; Cytosol; Dihydrotestosterone; Estrenes; Female; Humans; Male; Metribolone; Nandrolone; Pregnenediones; Prostate; Prostatic Hyperplasia; Rats; Rats, Inbred Strains; Receptors, Androgen; Receptors, Progesterone; Substrate Specificity; Uterus

Cytosols from human benign prostatic hypertrophy contained progestin-binding components which bound to R 5020, ORG 2058 and progesterone in high affinity fashion. Most of the protein bound to R 5020 was recovered in the precipitate with 0-30% saturation of ammonium sulfate. The R 5020-binding protein showed sedimentation coefficients of 3.6S and 8.4S, and was eluted in the void volume of a Sephadex G-200 column. This protein was clearly distinguished from the dihydrotestosterone-binding protein by its precipitability by ammonium sulfate, heat stability and susceptibility to delipidization. R 5020 and ORG 2058 binding were markedly inhibited by the addition of R 1881, therefore, most of the binding to progestin in cytosols from the benign prostatic hypertrophy seems to be also the sites for R 1881. Although nuclear extract by 0.4 M KCl showed R 1881 binding, the extract did not contain the R 5020-binding protein, and this suggested that the progestin-binding protein observed in the cytosols does not seem to be the steroid receptor.

Topics: Carrier Proteins; Cell Nucleus; Cytosol; Humans; Male; Norpregnenes; Pregnenediones; Progestins; Promegestone; Prostatic Hyperplasia; Receptors, Progesterone