Estrogen Action in the Mouse Uterus: Adrenal Modulation of Receptor Levels

Abstract

Adrenal regulation of estradiol receptor levels was demonstrated in the ovariectomized mouse uterus. After ovariectomy, cytosol receptor levels initially followed a cyclic pattern, with a periodicity of approximately 5 days and a range of range of 2.25-4.80 x 10(-13) mol estrogen receptor/100 micrograms DNA. Nuclear receptor levels showed marked fluctuations initially, but stabilized after day 15 at approximately 0.5 x 10(-13) mol/100 micrograms DNA. Microsomal receptor levels also changed with time, but at a lower level than the cytosol and nuclear fluctuations. Concurrent cyclic changes in uterine or vaginal histology were not observed. After simultaneous ovariectomy and adrenalectomy, cytosol estradiol receptor levels remained low (less than or equal to 1.5 x 10(-13) mol/100 micrograms DNA) from 5-24 days, with no fluctuations. Nuclear and microsomal receptor levels changed, but to a smaller extent than those in ovariectomized mice. Concurrent histological changes were not observed. The residual cytosolic estrogen receptor remaining in the ovariectomized-adrenalectomized mouse uterus was characterized. Scatchard analysis of saturation binding data showed one class of binding sites with a Ka of 6.56 nm-1 (n = 350 fmol/mg protein). This cytosol receptor sedimented at 8S on low salt sucrose density gradients. Receptor specificity was assessed by competitive equilibrium binding. The rank order of ligands was 17 beta-estradiol = diethylstilbestrol greater than nafoxidine. Progesterone and 5 alpha-dihydrotestosterone showed no appreciable binding activity. After the injection of estradiol (10 micrograms/kg), 80-90% of the total available estrogen receptor translocated to the nuclear compartment. This translocated receptor could stimulate uterine hypertrophy and hyperplasia, as assessed in 1- and 3-day bioassays, and was able to initiate progesterone receptor synthesis. From these results, we conclude that the adrenal can modulate uterine estrogen receptor levels.

Protection against atherosclerosis by estrogen is independent of plasma cholesterol levels in LDL receptor-deficient mice

“…Although the greater uterine weight of the exogenous 17␣-E 2 female mice was inconsistent with its known decreased potency at the classic estrogen receptor (21), this inconsistency can be ex- plained by the previously demonstrated differential effects of acute and chronic exposure and different capacity of 17␣-E 2 to induce its own metabolism. Specifically, chronic 17␣-E 2 exposure in rodents results in greater uterine size than acute 17␣-E 2 treatment (21,22), and 17␣-E 2 is less potent than 17␤-E 2 in inducing hepatic metabolism of estrogen compounds resulting in prolonged circulation of 17␣-E 2 (21). The high incidence of carcinoma of the cervix in exogenous 17␤-E 2 female mice was consistent with previously published data in mice of C57Bl background (reviewed in 23).…”

Ovarian and Adrenal Contributions to Postnatal Growth and Differentiation of the Rat Uterus

“…However, the levels reached during this period remain within the range observed during the rat estrous cycle [58] and are above the level necessary for a physiological response to E 2 in target tissues [59]. Similar uterine estrogen receptor levels are detected in adult mice after OVX, but OVX + ADX further reduces estrogen receptor levels [55,56]. Our data are consistent with the concept that sufficient estrogen receptor levels are present after OVX or OVX + ADX to allow a maximum E 2 -induced uterine weight response.…”

“…Adrenalrelated delay in puberty in the rat [53] is attributed to the adrenal cortex, which is the site of deoxycorticosterone biosynthesis [54]. Adrenal-mediated control of uterine estrogen receptor in adult mice [55,56] has been demonstrated. These results, combined with our findings of a greater decrease in uterine weight after OVX + ADX, compared to OVX alone, suggest a developmental role of the adrenal.…”

Υποδοχεις Οιστρογονων Και Προγεστερονης Των Νεοπλασματων Του Ενδομητριου

“…Τα επινεφρίδια μπορούν να επηρεάσουν τη συγκέντρωση των υπο δοχέων οιστρογόνων στη μήτρα όπως αποδείχτηκε σε πειράματα με πον τίκια από τα οποία είχαν αφαιρεθεί οι ωοθήκες (197). Κυκλική μεταβολή δε παρατηρήθηκε στους υποδοχείς οιστρογόνων και προγεστερόνης στη μήτρα και ωοθήκες αλλά προκλήθηκε υπερτροφία της μήτρας και αυξη μένη σύνθεση υποδοχέων προγεστερόνης κάτω από την επίδραση των επινεφριδίων ορμονών.…”