Frye C A
Department of Psychology, Biological Sciences and The Neurobiology Research Center, Social Sciences 112, The University at Albany-SUNY, 1400 Washington Avenue, Albany, New York 12222, USA.
Horm Behav. 2001 Sep;40(2):226-33. doi: 10.1006/hbeh.2001.1674.
Progesterone (P(4)) in the ventromedial hypothalamus (VMH) and ventral tegmental (VTA) is important for facilitation of lordosis; however, P(4)'s actions in these brain areas are different. Using lordosis in rodents as in vivo experimental models, we have examined the effects progestins exert in the midbrain and hypothalamus. Localization and blocker studies indicate that P(4)'s actions in the VMH require intracellular progestin receptors (PRs) but in the VTA they do not. Progestins that have rapid, membrane effects, and/or are devoid of affinity for PRs, facilitate lordosis when applied to the VTA. Manipulation of GABA and/or GABA(A)/benzodiazepine receptor complexes (GBRs) in the VTA alter lordosis, which suggests that progestins may interact with GBRs to facilitate receptivity by enhancing the function of GABAergic neurons. Interfering with P(4)'s metabolism to 5 alpha-pregnan-3 alpha-ol-20-one (3 alpha,5 alpha-THP), the most effective endogenous positive modulator of GBRs, or the biosynthesis of the neurosteroid 3 alpha,5 alpha-THP in the VTA attenuates female sexual behavior in rodents. Stimulation of mitochondrial benzodiazepine receptors (MBRs), which enhance neurosteroid production, by infusions of a MBR agonist to the VTA enhances lordosis. 3 alpha,5 alpha-THP is increased in the midbrain of mated > proestrous > diestrous rodents. These data suggest that 3 alpha,5 alpha-THP has a proximate modulatory role on lordosis. In summary, the actions of P(4) in the VTA are different from those in the VMH that involve PRs. In the VTA, P(4) may facilitate lordosis following metabolism to and/or biosynthesis of 3 alpha,5 alpha-THP, which may have subsequent actions at GBRs and/or MBRs to acutely modulate female sexual behavior in rodents.
腹内侧下丘脑（VMH）和腹侧被盖区（VTA）中的孕酮（P(4)）对于促进脊柱前凸很重要；然而，P(4)在这些脑区的作用有所不同。我们以啮齿动物的脊柱前凸作为体内实验模型，研究了孕激素在中脑和下丘脑中的作用。定位和阻断剂研究表明，P(4)在VMH中的作用需要细胞内孕激素受体（PRs），但在VTA中则不需要。具有快速膜效应和/或对PRs缺乏亲和力的孕激素，应用于VTA时可促进脊柱前凸。对VTA中的γ-氨基丁酸（GABA）和/或GABA(A)/苯二氮䓬受体复合物（GBRs）进行操作会改变脊柱前凸，这表明孕激素可能与GBRs相互作用，通过增强GABA能神经元的功能来促进接受性。干扰P(4)代谢为5α-孕烷-3α-醇-20-酮（3α,5α-THP），即GBRs最有效的内源性正向调节剂，或VTA中神经甾体3α,5α-THP的生物合成，会减弱啮齿动物的雌性性行为。通过向VTA注入MBR激动剂刺激线粒体苯二氮䓬受体（MBRs），可增强神经甾体的产生，从而增强脊柱前凸。在交配的>动情前期>动情间期的啮齿动物中脑，3α,5α-THP会增加。这些数据表明，3α,5α-THP对脊柱前凸具有直接的调节作用。总之，P(4)在VTA中的作用与在涉及PRs的VMH中的作用不同。在VTA中，P(4)可能在代谢为和/或生物合成为3α,5α-THP后促进脊柱前凸，3α,5α-THP随后可能在GBRs和/或MBRs发挥作用，以急性调节啮齿动物的雌性性行为。
