Frye C A
Department of Psychology, Biological Sciences and The Center for Neuroscience Research, The University at Albany, SUNY, Albany, NY 12222, USA.
Brain Res Brain Res Rev. 2001 Nov;37(1-3):201-22. doi: 10.1016/s0165-0173(01)00119-9.
Progestins and androgens modulate sexual receptivity in rodents, in part through mechanisms independent of traditional intracellular steroid receptors. Progesterone (PROG) in the ventromedial hypothalamus (VMH) and ventral tegmental (VTA) facilitates lordosis but has different actions in these brain areas. Primarily using lordosis in rodents as an in vivo experimental model, we have examined the effects that progestins exert in the midbrain and hypothalamus. Localization and blocker studies indicate that PROG'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 alters lordosis, which suggests that progestins may interact with GBRs to facilitate receptivity by enhancing the function of GABAergic neurons. Interfering with PROG's metabolism to, or the biosynthesis of, 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha,5alpha-TH PROG or allopregnanolone), the most effective endogenous GBR agonist, in the VTA attenuates female sexual behavior in rodents. Stimulation of mitochondrial benzodiazepine receptors (MBRs), which enhances neurosteroid production, by infusions of an MBR agonist to the VTA enhances lordosis. 3alpha,5alpha-TH PROG is increased in the midbrain of mated>proestrous>diestrous rodents. These data suggest that in the VTA, PROG may facilitate lordosis following metabolism to and/or biosynthesis of 3alpha,5alpha-TH PROG, which may have subsequent actions at GBRs and/or MBRs to acutely modulate female sexual behavior in rodents. The 3alpha-hydroxysteroid oxidoreduced metabolite of dihydrotestosterone (DHT), 5alpha-androstane-3alpha,17beta-diol (3alpha-androstanediol), is important for termination of sexual receptivity in rodents and has these effects in the absence of functional intracellular androgens receptors. As well, altering GBR function in the hypothalamus can influence 3alpha-androstanediol's inhibition of sexual receptivity. Through actions in the hypothalamus that are independent of intracellular androgen receptors but involving GBRs, 3alpha-androstanediol inhibits lordosis. These findings suggest that the PROG metabolite and pregnane neurosteroid, 3alpha,5alpha-TH PROG, and the testosterone metabolite and androstane neurosteroid, 3alpha-androstanediol, can have proximate influences on lordosis that is via nonclassical actions at intracellular steroid receptors.
孕激素和雄激素可调节啮齿动物的性接受能力，部分是通过独立于传统细胞内类固醇受体的机制。腹内侧下丘脑（VMH）和腹侧被盖区（VTA）中的孕酮（PROG）可促进脊柱前凸，但在这些脑区具有不同作用。我们主要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产生的影响。定位和阻断剂研究表明，PROG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性接受能力。干扰VTA中最有效的内源性GBR激动剂3α-羟基-5α-孕烷-20-酮（3α,5α-四氢孕酮或别孕烯醇酮）的PROG代谢或生物合成，会减弱啮齿动物的雌性性行为。通过向VTA注射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内，3α,5α-四氢孕酮含量增加。这些数据表明，在VTA中，PROG可能在代谢为和/或生物合成3α,5α-四氢孕酮后促进脊柱前凸，后者可能随后作用于GBRs和/或MBRs，以急性调节啮齿动物的雌性性行为。二氢睾酮（DHT）的3α-羟基类固醇氧化还原代谢产物5α-雄甾烷-3α,17β-二醇（3α-雄甾二醇）对于啮齿动物性接受能力的终止很重要，并且在没有功能性细胞内雄激素受体的情况下具有这些作用。同样，改变下丘脑GBR的功能会影响3α-雄甾二醇对性接受能力的抑制作用。通过在下丘脑中独立于细胞内雄激素受体但涉及GBRs的作用，3α-雄甾二醇抑制脊柱前凸。这些发现表明，PROG代谢产物和孕烷神经甾体3α,5α-四氢孕酮，以及睾酮代谢产物和雄甾烷神经甾体3α-雄甾二醇，可通过对细胞内类固醇受体的非经典作用对脊柱前凸产生直接影响。
