Cytoplasmic Progestin Binding in Rat Adipose Tissues*

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Abstract
Ovarian hormones, including progestins, have important effects on body fat levels in rats, but the mechanisms by which progestins exert their effects on adiposity are not known. We have found high affinity, estrogen-inducible, progestin-specific binding of [3H]R5020 (3H-labeled 17α,21-dimethyl-19-norpregna- 4,9-diene-3,20-dione), a synthetic progestin, in the cytoplasmic fraction of adipose tissues from ovariectomized-adrenalectomized rate. Saturation analysis indicates a Kd of 8.5 × 10-10 M in rats primed with 17β-estradiol benzoate (E2B). In parametrial adipose tissue, the number of binding sites in E2B-primed rats was approximately 26 times that in unprimed rats. Binding was inhibited more by progestins (R5020 > progesterone > 5αdihydroprogesterone) than by 17β-estradiol, 5α-dihydrotestosterone, or corticosterone. Pronase inhibited cytoplasmic [3H]- R5020 binding by 95%, but DNase and RNae were without effect. After a single injection of 2 μg E2B, very little [3H]R5020 binding was found at 6 h, while peak amounts of binding were found 12–36 h after administration of E2B. A single injection of E2B (2 μg), CI-628 (50 μg; α-(4-pyrrolidino ethoxy)phenyl-4- methoxy-α′-nitrostilbene monocitrate) or nafoxidine [50 μg; l-(2- [p-(3,4-dihydro-6-methoxy-2-phenylnaphth-l-yl) - phenoxy]ethyl) pyrrolidine] depleted 17β-[3H]estradiol-binding sites and induced [3H]R5020-binding sites, but estrone benzoate (2 μg) and MER-25 [500 μg; l-(p-2-diethylaminoethoxyphenyl)-l-phenyl-2- methoxyphenylethanol] were without effect. Efficacy of in vivo depletion of available cytoplasmic progestin receptors by 500 μg progestin was in the same order as the affinity of the compounds for the binding sites in vitro (R5020 > progesterone > 5αdihydroprogesterone). [3H]R5020-binding sites were found in all adipose tissues studied, including abdominal, sc, and brown fat. However, regional differences in absolute levels of E2B-induced progestin binding were found, as were differences in the magnitude of induction of progestin-binding sites (E2B-induced/basal). Further analyses revealed a highly significant correlation between estrogen receptor concentrations and the magnitude of induction of progestin receptors in specific adipose tissues. These data indicate that adipose tissues might be bona fide target tissues for ovarian hormones in rats. A possible mechanism by which these steroids might exert direct effects on adipose tissues is discussed.

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