Amico J A, Crowley R S, Insel T R, Thomas A, O'Keefe J A
University of Pittsburgh School of Medicine, PA, USA.
Adv Exp Med Biol. 1995;395:23-35.
Oxytocin (OT) has been implicated in reproductive events. Gonadal steroids, which are also essential for reproduction, may in these instances influence the expression of the OT gene. The relationship between gonadal steroids and OT expression is incompletely understood. First, although estrogen (E) induces OT expression in heterologous in vitro systems and the OT gene contains an estrogen response element, evidence for a stimulatory effect of E upon OT mRNA in vivo as in the rat hypothalamus has been lacking. Second, an enhanced and coordinated expression of OT and vasopressin (AVP), mRNA during late pregnancy and lactation is not expected. This is especially true in lactation, during which suckling selectively activates OT, not AVP, neurons. We now report that E does increase OT mRNA levels in the rat hypothalamus. Ovariectomized rats were implanted initially with E, followed by progesterone (P) 48 hrs later; both were sustained for 12 days and the P implants were removed 48 hrs prior to sacrifice. By in situ and Northern blot hybridizations, OT, but not AVP, mRNA was increased in the hypothalamus of animals receiving this regimen compared to sham treated cohorts. A similar phenomenon associated with exposure to E and P followed by P withdrawal occurs in physiologic states such as day 21 of pregnancy, day 10-12 of lactation, and with interruption of the suckling stimulus for 48 hrs. If E was not administered or if P was not withdrawn prior to sacrifice, no increase was found in OT mRNA. Our data highlight the pivotal role of P withdrawal in the induction of the hypothalamic OT gene in the E-primed rat.
催产素（OT）与生殖活动有关。性腺类固醇对生殖也至关重要，在这些情况下可能会影响OT基因的表达。性腺类固醇与OT表达之间的关系尚未完全明了。首先，尽管雌激素（E）在异源体外系统中可诱导OT表达，且OT基因含有雌激素反应元件，但在大鼠下丘脑等体内环境中，E对OT mRNA具有刺激作用的证据一直缺乏。其次，在妊娠晚期和哺乳期，OT和血管加压素（AVP）mRNA的表达增强且协调，这是出乎意料的。在哺乳期尤其如此，在此期间，哺乳选择性地激活OT神经元，而非AVP神经元。我们现在报告，E确实会增加大鼠下丘脑的OT mRNA水平。对卵巢切除的大鼠，最初植入E，48小时后再植入孕酮（P）；两者均持续12天，在处死前48小时取出P植入物。通过原位杂交和Northern印迹杂交发现，与假手术对照组相比，接受该方案的动物下丘脑内OT mRNA增加，而AVP mRNA未增加。在生理状态下，如妊娠第21天、哺乳第10 - 12天以及哺乳刺激中断48小时，会出现类似的与暴露于E和P后再撤去P相关的现象。如果在处死前未给予E或未撤去P，则未发现OT mRNA增加。我们的数据突出了撤去P在雌激素预处理大鼠下丘脑OT基因诱导中的关键作用。
