Lee Y, Voogt J L
Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City 66160-7401, USA.
Endocrinology. 1999 May;140(5):2159-66. doi: 10.1210/endo.140.5.6730.
PRL in the rat exerts its luteotropic action during the first half of pregnancy. After midpregnancy, placental lactogens (PLs) take the place of PRL to stimulate progesterone secretion from the corpus luteum. Simultaneously, PLs trigger a negative feedback on PRL secretion. However, the brain mechanisms for the negative feedback induced by PLs are not fully understood. Here, we report changes in plasma PRL levels, tuberoinfundibular dopaminergic (TIDA) neuronal activity as measured by Fos-related antigen (FRA)/tyrosine hydroxylase (TH) immunoreactivity, and TH catalytic activity as measured by dihydroxyphenylalanine (DOPA) accumulation in the stalk-median eminence (SME) after experimental manipulation of PL levels. On day 4 of pregnancy, animals received Rcho-1 cells intracerebroventricularly (i.c.v.) to increase the level of PLs in the brain or HRP-1 cells as controls. On day 12 of pregnancy, hysterectomy alone or i.c.v. HRP-1 injection plus hysterectomy were performed to remove the source of PLs. Rcho-1 i.c.v. injection plus hysterectomy were performed to examine the effect of replacement of the PL source. Sham-hysterectomized animals were used as a control group. Animals were killed 2 days after each treatment at 0200 and 1800 h, which represent the peak times of PRL surges, and at 1400 h, which represents the intersurge time, by either transcardial perfusion for FRA/TH immunocytochemistry or decapitation 30 min after NSD 1015 injection to assess DOPA accumulation with HPLC-electrochemical detection. Rcho-1 cells completely abolished PRL surges on day 6 of pregnancy and increased the percentage of FRA/TH immunoreactivity in the dorsomedial, ventrolateral, and caudal subdivisions of the arcuate nucleus. This change in neuronal activity reflected the amount of DOPA accumulation in the SME, which was high at all time points. On day 14 of pregnancy, removal of the PL source by hysterectomy resulted in increased PRL levels and decreased neuronal activity of TIDA neurons at all three time points. Similar profiles were observed in animals that received i.c.v. HRP-1 injection plus hysterectomy. Replacement of the source of PL with Rcho-1 cells in hysterectomized rats resulted in low PRL secretion, high neuronal activity of TIDA neurons, and high TH catalytic activity. These patterns were the same as those in sham-operated animals. Our results demonstrate that PLs induce an increase in the neuronal activity of dopaminergic neurons, as measured by FRA/TH immunoreactivity and TH catalytic activity in the SME. Removal of the PL source elevates plasma PRL levels at all times during the second half of pregnancy and does not restore PRL surges.
大鼠体内的催乳素（PRL）在妊娠前半期发挥其促黄体作用。妊娠中期后，胎盘催乳素（PLs）取代PRL来刺激黄体分泌孕酮。同时，PLs对PRL分泌触发负反馈。然而，PLs诱导负反馈的脑机制尚未完全了解。在此，我们报告了通过实验操纵PL水平后，血浆PRL水平的变化、通过Fos相关抗原（FRA）/酪氨酸羟化酶（TH）免疫反应性测量的结节漏斗多巴胺能（TIDA）神经元活动，以及通过茎 - 正中隆起（SME）中二羟基苯丙氨酸（DOPA）积累测量的TH催化活性。在妊娠第4天，动物经脑室内（i.c.v.）注射Rcho - 1细胞以增加脑内PLs水平，或注射HRP - 1细胞作为对照。在妊娠第12天，单独进行子宫切除术或i.c.v.注射HRP - 1加子宫切除术以去除PLs来源。进行i.c.v.注射Rcho - 1加子宫切除术以检查PLs来源替代的效果。假手术切除子宫的动物用作对照组。在每次处理后2天的02:00和18:00（代表PRL分泌高峰时间）以及14:00（代表分泌高峰间期）处死动物，通过经心灌注进行FRA/TH免疫细胞化学，或在注射NSD 1015后30分钟断头，用高效液相色谱 - 电化学检测评估DOPA积累。Rcho - 1细胞在妊娠第6天完全消除了PRL分泌高峰，并增加了弓状核背内侧、腹外侧和尾侧亚区FRA/TH免疫反应性的百分比。这种神经元活动的变化反映了SME中DOPA积累量，在所有时间点都很高。在妊娠第14天，子宫切除术去除PLs来源导致在所有三个时间点PRL水平升高和TIDA神经元活动降低。在接受i.c.v.注射HRP - 1加子宫切除术的动物中观察到类似的情况。在子宫切除的大鼠中用Rcho - 1细胞替代PLs来源导致PRL分泌低、TIDA神经元活动高和TH催化活性高。这些模式与假手术动物相同。我们的结果表明，通过SME中的FRA/TH免疫反应性和TH催化活性测量，PLs诱导多巴胺能神经元的神经元活动增加。去除PLs来源在妊娠后半期的所有时间都升高血浆PRL水平，并且不能恢复PRL分泌高峰。
