Neonatal Deprivation of Maternal Touch May Suppress Ornithine Decarboxylase via Downregulation of the Proto-oncogenes c-myc...

Shiying Wang, Jorge V. Bartolome, and Saul M. Schanberg

Department of Pharmacology, Duke University, Durham, North Carolina 27710

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 IO-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 OK 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 O/X enzyme activity and c-myc, max, and ODC mRNAs but had little effect on expression of the other proto-oncogenes. PRL-induced stimulation of OK, c-myc, and max mRNAs also was depressed in neonates placed with an anesthetized lactating dam (touch-deprived) but not in pups placed with nippleligated 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 2.5d-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 O/X 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.