The neurosteroid allopregnanolone modulates oxytocin expression in the hypothalamic paraventricular nucleus

被引:28
作者
Blyth, BJ
Hauger, RL
Purdy, RH
Amico, JA
机构
[1] Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA
[2] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15261 USA
[3] Dept Vet Affairs Med Ctr, Pittsburgh, PA 15261 USA
[4] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92061 USA
[5] Dept Vet Affairs Med Ctr, San Diego, CA 92061 USA
关键词
estrogen; gamma aminobutyric acid; progesterone;
D O I
10.1152/ajpregu.2000.278.3.R684
中图分类号
Q4 [生理学];
学科分类号
071003 [生理学];
摘要
Virgin, ovariectomized rats exposed to 2 wk of sequential estradiol (E-2) and progesterone (P) followed by P withdrawal have increased hypothalamic oxytocin (OT) mRNA and peptide levels relative to sham-treated animals. This increase is prevented if P is sustained. In the central nervous system, P is metabolized to the neurosteroid allopregnanolone (3 alpha-hydroxy-5 alpha-pregnan-20-one), which exerts effects by acting as a positive allosteric modulator of GABA(A) receptor/Cl--channel complexes. In the present study, ovariectomized rats that received sequential E-2 and P for 2 wk followed by P withdrawal were administered allopregnanolone at the time of P withdrawal. Hypothalamic and plasma allopregnanolone concentrations, serum E-2 and P concentrations, and hypothalamic OT mRNA levels were measured at death. Steroid-induced increases in OT mRNA were attenuated in animals treated with allopregnanolone at the time of P withdrawal. The results suggest that allopregnanolone plays an important modulatory role in steroid-mediated increases in hypothalamic OT.
引用
收藏
页码:R684 / R691
页数:8
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