PKC alpha mediates maternal touch regulation of growth-related gene expression in infant rats.
During short-term periods of separation of rat pups from their mothers, the loss of certain sensory signals suppresses the increase in ornithine decarboxylase (ODC) gene expression induced by the growth-promoting hormones prolactin (PRL) and growth hormone (GH). Here, we identify a molecular mechanism through which maternal separation (MS) curtails ODC expression. Our results demonstrate that the absence of specific tactile stimuli provided by the mother limits PRL-evoked stimulation of ODC biosynthesis by interfering with sn-1,2-diacylglycerol's (DAG) ability to activate protein kinase Calpha (PKCalpha) and consequently c-myc mRNA and max mRNA expression. The proteins encoded by these proto-oncogenes function as direct transactivators of the ODC gene. As ODC activity is obligatory for normal cell replication and differentiation, PKCalpha activation by DAG represents an important control point at which 'nurturing touch' regulates growth and development of the neonate. Such a mechanism can explain the maladaptive consequences of disrupting mother-infant tactile interactions as occurs in isolated premature babies. Also, it could provide a basis for developing therapeutic interventions to maximize growth potential in children failing-to-thrive despite normal maternal care.
Schanberg
Saul M
SM
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA. schan003@mc.duke.edu
Ingledue
Vickie F
VF
Lee
Joanna Y
JY
Hannun
Yusuf A
YA
Bartolome
Jorge V
JV
D000818:Animals; D000831:Animals, Newborn / Q000235:genetics* / Q000254:growth & development*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D013006:Growth Hormone / Q000096:biosynthesis; D008099:Liver / Q000254:growth & development / Q000378:metabolism; D008426:Maternal Deprivation; D009955:Ornithine Decarboxylase / Q000096:biosynthesis; D011388:Prolactin / Q000096:biosynthesis; D011493:Protein Kinase C / Q000096:biosynthesis*; D051571:Protein Kinase C-alpha; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D015398:Signal Transduction / Q000235:genetics; D014110:Touch / Q000502:physiology*
D012333:RNA, Messenger; D011388:Prolactin; D013006:Growth Hormone; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D009955:Ornithine Decarboxylase