Ferretti C, Blengio M, Vigna I, Ghi P, Genazzani E
Istituto di Farmacologia e Terapia Sperimentale, Università di Torino, Italy.
Brain Res. 1992 Feb 7;571(2):212-7. doi: 10.1016/0006-8993(92)90657-u.
Since estradiol (E2) either increases or reduces the number of dopamine receptors in the corpus striatum of adult rats, depending on the dose and length of administration, the sensitivity of the two receptor subpopulations (D1 and D2) to E2 during ontogenesis was investigated. Rats of both sexes received either 10 micrograms/kg E2 for 3 days or 50 micrograms/kg for 6 days, and were sacrificed at the age of 15, 21, 40 and 120 days. D1 receptors (identified by [3H]SCH 23390 binding) displayed no changes in density and affinity in function of age, sex or E2 dose, whereas the D2 receptors (identified by [3H]spiperone binding) fell after the lower dose in all groups, and the higher dose resulted in supersensitivity in males of all ages, but only in the 15-day-old females. These findings show that the effect of E2 is bivalent on D2 density only. The effect of its brief administration at a low dose is not sex-dependent, whereas at higher doses administered for longer periods it appears to involve mechanisms linked to sexual differentiation after birth.
由于雌二醇(E2)根据给药剂量和时长的不同,会增加或减少成年大鼠纹状体中多巴胺受体的数量,因此研究了这两种受体亚群(D1和D2)在个体发育过程中对E2的敏感性。雌雄大鼠均接受10微克/千克E2,给药3天,或50微克/千克,给药6天,并在15、21、40和120日龄时处死。D1受体(通过[3H]SCH 23390结合鉴定)的密度和亲和力在年龄、性别或E2剂量方面均无变化,而D2受体(通过[3H]螺哌隆结合鉴定)在所有组中,较低剂量给药后数量下降,较高剂量给药导致所有年龄段的雄性大鼠超敏,但仅15日龄雌性大鼠出现超敏。这些发现表明,E2仅对D2密度具有二价效应。低剂量短期给药的效应不依赖性别,而高剂量长期给药的效应似乎涉及出生后与性别分化相关的机制。