Frye Cheryl A, Rhodes Madeline E
Department of Psychology, The University at Albany-SUNY, Albany, NY 12222, USA.
Brain Res. 2005 Mar 15;1038(1):59-68. doi: 10.1016/j.brainres.2005.01.014.
5 alpha-Pregnan-3 alpha-ol-20-one (3 alpha,5 alpha-THP), progesterone (P4)'s 5 alpha-reduced, 3 alpha-hydroxysteroid oxidoreduced product, facilitates lordosis of rodents in part via agonist-like actions at GABA(A)/benzodiazepine receptor complexes in the ventral tegmental area (VTA). Whether 3 alpha,5 alpha-THP influences another reproductively-relevant behavior, lateral displacement, of hamsters was investigated. Lateral displacement is the movement that female hamsters make with their perineum towards male-like tactile stimulation. This behavior facilitates, and is essential for, successful mating. Hamsters in behavioral estrus had greater lateral displacement responses when endogenous progestin levels were elevated compared to when progestin levels were lower. Administration of P4, a prohormone for 3 alpha,5 alpha-THP, dose-dependently (500 > 200 > 100, 50, or 0 microg) enhanced lateral displacement of ovariectomized hamsters that had been primed with SC estradiol benzoate (5 or 10 microg). Inhibiting P4's metabolism to 3 alpha,5 alpha-THP by co-administering finasteride, a 5 alpha-reductase inhibitor, or indomethacin, a 3 alpha-hydroxysteroid oxidoreductase inhibitor, either systemically or to the VTA, significantly decreased lateral displacement and midbrain progestin levels of naturally receptive or hormone-primed hamsters compared to controls. These data suggest that lateral displacement is progestin-sensitive and requires the formation of 3 alpha,5 alpha-THP in the midbrain VTA.
5α-孕烷-3α-醇-20-酮（3α,5α-四氢孕酮，3α,5α-THP）是孕酮（P4）的5α还原、3α羟基甾体氧化还原产物，它部分通过在腹侧被盖区（VTA）的GABA(A)/苯二氮䓬受体复合物上发挥类似激动剂的作用来促进啮齿动物的脊柱前凸。本研究调查了3α,5α-THP是否会影响仓鼠另一种与生殖相关的行为——侧向移位。侧向移位是雌性仓鼠用会阴朝向类似雄性的触觉刺激做出的动作。这种行为对成功交配具有促进作用且必不可少。与孕激素水平较低时相比，处于行为发情期的仓鼠在体内孕激素水平升高时具有更强的侧向移位反应。给予3α,5α-THP的前体激素P4，剂量依赖性地（500>200>100、50或0微克）增强了已用皮下注射苯甲酸雌二醇（5或10微克）预处理的去卵巢仓鼠的侧向移位。通过全身或向VTA共同给予5α还原酶抑制剂非那雄胺或3α羟基甾体氧化还原酶抑制剂吲哚美辛来抑制P4向3α,5α-THP的代谢，与对照组相比，显著降低了自然接受刺激或激素预处理的仓鼠的侧向移位和中脑孕激素水平。这些数据表明，侧向移位对孕激素敏感，并且需要在中脑VTA中形成3α,5α-THP。
