Wang S, Bartolome J V, Schanberg S M
Department of Pharmacology, Duke University, Durham, North Carolina 27710, USA.
J Neurosci. 1996 Jan 15;16(2):836-42. doi: 10.1523/JNEUROSCI.16-02-00836.1996.
Previously, we have shown that short-term (1 hr) separation of neonatal rats from their mother (MS) suppresses basal ornithine decarboxylase (ODC) synthesis and tissue ODC response to trophic factors. This effect in the pup is caused by absence of maternal tactile stimulation (touch) but not from lack of maternal nutrients (food). This study was performed to examine in 10-d-old rats whether maternal touch deprivation affects expression of certain hepatic proto-oncogenes, the protein products of which are known to interact with the regulatory region of the ODC gene. Prolactin (PRL) injected subcutaneously increased hepatic ODC activity as well as mRNA levels of ODC and the proto-oncogenes c-fos, c-jun, junB, junD, c-myc, and max. MS significantly suppressed PRL-induced increases in ODC enzyme activity and c-myc, max, and ODC mRNAs but had little effect on expression of the other proto-oncogenes. PRL-induced stimulation of ODC, c-myc, and max mRNAs also was depressed in neonates placed with an anesthetized lactating dam (touch-deprived) but not in pups placed with nipple-ligated dams (food-deprived). Furthermore, unlike its effect on preweanling-age pups (< 20 d old), MS did not alter expression of either ODC or c-myc mRNAs in 25-d-old pups acutely separated from their mother. These findings indicate that suppression of ODC gene transcription in the neonatal pup during MS may be mediated by downregulation of the ODC gene transactivator proto-oncogenes c-myc and max. They are also consistent with our previous observation that lack of maternal touch, but not maternal milk, initiates the physiological alterations induced by MS.
此前,我们已经表明,新生大鼠与母亲短期(1小时)分离(母子分离)会抑制基础鸟氨酸脱羧酶(ODC)的合成以及组织ODC对营养因子的反应。幼崽身上的这种效应是由缺乏母体触觉刺激(触摸)引起的,而非缺乏母体营养(食物)。本研究旨在检查10日龄大鼠中母体触摸剥夺是否会影响某些肝原癌基因的表达,已知这些基因的蛋白质产物可与ODC基因的调控区域相互作用。皮下注射催乳素(PRL)可增加肝脏ODC活性以及ODC、原癌基因c-fos、c-jun、junB、junD、c-myc和max的mRNA水平。母子分离显著抑制了PRL诱导的ODC酶活性以及c-myc、max和ODC mRNA的增加,但对其他原癌基因的表达影响很小。在与麻醉的泌乳母鼠放置在一起(触觉剥夺)的新生大鼠中,PRL诱导的ODC、c-myc和max mRNA的刺激也受到抑制,但在与乳头结扎母鼠放置在一起(食物剥夺)的幼崽中则没有。此外,与对断奶前幼崽(<20日龄)的影响不同,母子分离并没有改变25日龄幼崽急性与母亲分离后ODC或c-myc mRNA的表达。这些发现表明,母子分离期间新生幼崽中ODC基因转录的抑制可能是由ODC基因反式激活原癌基因c-myc和max的下调介导的。它们也与我们之前的观察结果一致,即缺乏母体触摸而非母体乳汁会引发母子分离诱导的生理变化。