Frye C A, Vongher J M
Department of Psychology, SUNY, 1400 Washington Avenue, Albany, NY 12222,
Brain Res. 1999 Jan 9;815(2):259-69. doi: 10.1016/s0006-8993(98)01132-9.
Ovariectomized (ovx) mice require both estradiol (E2) and progesterone (P) administration to reinstate feminine sexual behavior (lordosis). The importance of P's actions at E2-induced intracellular progestin receptors (PRs) to facilitate lordosis was investigated in PR knockout (PRKO) mice, PRKO's wild type littermates (C57X129), and wild type C57BL/6J (C57) mice. Subjects were ovx, E2-primed (0.5 microg) and tested following intravenous (i. v.) and intercereberal P. Intravenous P (200 microg) significantly increased lordosis of all mice within 10 min of P, but vehicle infusion did not (Experiment 1). Intravenous P significantly increased the amount and duration and reduced the latency of lordosis, over that seen with vehicle infusion, in PRKO and wild type mice. Whole brain concentrations of P and its 5alpha-reduced metabolite, 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP), which has low affinity for intracellular PRs, were also increased following P compared to vehicle infusion. Progesterone, but not vehicle infusions, significantly increased the number of PR-immunoreactive (PR-IR) cells in the ventromedial hypothalamus (VMH) of C57 and C57X129 mice and increased number of 3alpha, 5alpha-THP-immunoreactive (3alpha,5alpha-THP-IR) cells in the ventral tegmental area (VTA) of all mice. In Experiment 2, P conjugated to bovine serum albumin (P:BSA) increased lordosis when applied bilaterally to both the VMH and VTA of E2-primed mice more than BSA implants. Progesterone implants increased the number of PR-IR cells in the VMH of C57 and C57X129 mice and the number of 3alpha,5alpha-THP-IR cells in the VTA of all mice. The rapid facilitation of lordosis with i.v. P infusion and increases in lordosis when P's effects are relegated to the membrane in the VMH and VTA of PRKO and wild type mice suggest that P may facilitate lordosis through actions at substrates other than intracellular PRs. The present findings suggest a role of 3alpha,5alpha-THP.
去卵巢（ovx）小鼠需要同时给予雌二醇（E2）和孕酮（P）才能恢复雌性性行为（脊柱前凸）。在孕酮受体基因敲除（PRKO）小鼠、PRKO的野生型同窝小鼠（C57X129）以及野生型C57BL/6J（C57）小鼠中，研究了P作用于E2诱导的细胞内孕激素受体（PRs）以促进脊柱前凸的重要性。实验对象为去卵巢、经E2预处理（0.5微克）的小鼠，在静脉注射（i.v.）和脑室内注射P后进行测试。静脉注射P（200微克）在注射后10分钟内显著增加了所有小鼠的脊柱前凸，但注射溶媒则没有（实验1）。与注射溶媒相比，静脉注射P显著增加了PRKO和野生型小鼠脊柱前凸的次数和持续时间，并缩短了潜伏期。与注射溶媒相比，注射P后，全脑P及其5α-还原代谢产物5α-孕烷-3α-醇-20-酮（3α,5α-四氢孕酮，3alpha,5alpha-THP）的浓度也有所增加，3alpha,5alpha-THP对细胞内PRs的亲和力较低。孕酮注射而非溶媒注射，显著增加了C57和C57X129小鼠腹内侧下丘脑（VMH）中PR免疫反应性（PR-IR）细胞的数量，以及所有小鼠腹侧被盖区（VTA）中3α,5α-THP免疫反应性（3alpha,5alpha-THP-IR）细胞的数量。在实验2中，与牛血清白蛋白结合的P（P:BSA）双侧植入E2预处理小鼠的VMH和VTA时，比植入BSA更能增加脊柱前凸。孕酮植入增加了C57和C57X129小鼠VMH中PR-IR细胞的数量以及所有小鼠VTA中3alpha,5alpha-THP-IR细胞的数量。静脉注射P快速促进脊柱前凸，以及当P的作用定位于PRKO和野生型小鼠的VMH和VTA的膜上时脊柱前凸增加，这表明P可能通过作用于细胞内PRs以外的底物来促进脊柱前凸。目前的研究结果表明3alpha,5alpha-THP发挥了作用。
