Abstract
Estradiol (E(2)) and progesterone (P(4)) have classical, steroid receptor-mediated actions in the ventral medial hypothalamus to initiate lordosis of female rodents. P(4) and the P(4) metabolite and neurosteroid, 5 alpha-pregnan-3 alpha-ol-20-one (3 alpha,5 alpha-THP), have non-classical actions in the midbrain ventral tegmental area (VTA) to modulate lordosis. We investigated the role of steroid hormone binding globulin (SHBG) and oxytocin in the VTA as mechanisms for these effects. Rats were ovariectomized and surgically implanted with bilateral guide cannulae aimed at the VTA. Rats were E(2)-primed (10 microg/0.2 ml) at hour 0, and administered 100 (Experiments 1 and 2), 500 (Experiment 3), or 0 (Experiment 1 and 4) microg/0.2 ml P(4) at hour 44. At hour 47.5, rats received bilateral infusions to the VTA, and were tested for lordosis 30 min post-infusion. Experiment 1: rats were infused with sterile saline vehicle or SHBG (4.5 pg/microl) to the VTA. SHBG, compared to vehicle, to the midbrain VTA significantly increased lordosis in E(2)- and P(4)-primed, but not E(2)-primed, rats. Experiment 2: rats were infused with bilateral infusions of sterile saline or oxytocin (1.0 pg/microl). Compared to vehicle, oxytocin to the VTA increased lordosis. Experiment 3: rats were administered bilateral intra-VTA infusions of saline or an oxytocin receptor antagonist, d(CH(2))(5),[TYr(ME)(2),Thr(4),Tyr-NH(9,2)] (1.2 pg/microl). Compared to vehicle, the oxytocin receptor antagonist to the VTA attenuated lordosis of E(2)- and P(4)-primed rats. Experiment 4: rats were E(2)-primed and infused with vehicle, oxytocin, or oxytocin antagonist. There were no effects of these manipulations in E(2)-primed rats. Thus, SHBG and/or oxytocin may have actions in the VTA for progestogen-facilitated lordosis.