Tobacco Documents Online

THE COUNCIL FOR TOBACCO RESEARCH-U.S.r1., INC. 900 TIIIRD .LVENUE NEW YORK. N.Y. 10022 Memorandum To: Dr. J.F.Glenn and Staff From: D.H.Ford Re: Site visit with Dr. L.fVilla-Komaroff, Children's Hospital Medical Center, Boston, Sept. 21, 1988. Grant No.2136R1 entitled "Control of neuropeptide synthesis in rodents." Goals: To determine how different cell types regulate trans- cription of the somatostatin gene and to characterize the region of the gene which controls its tissue specific expression in dorsal root gangion cells, medullary thyroid cells and adrenal medullary cells in the mouse. Results: The three cells types in which Dr. Villa-Komaroff is interAed are all derivitives of the neural crest which differ considerably in their use of somatostatin, selectively activating or suppressing its synthesis as they differentiate. During the past year Dr. Villa-Komaraoff has made considerable progress in the analysis of the gene for somatostatin. She hopes to complete this aspect of the study during the second year of her program and then determine if the somatostatin message is the same in each of the three cell types she is studying in both in vitro and in vivo investigations. She also plans to determine which inJ vitro culture condition ~s most favorable for expression of the gene in each of the three cell types. She further plans to. determine what hormones or substances induce or suppress somatostatin production or release. Comment: Now that the initial efforts, which were to sequence the mouse gene for somatostatin are nearly completed (90% of the sequence of the 2000-base region 3' to the genel, she will be moving on to the other aspects of the study. At the moment her group is subcloning and sequencing the area immediately 5' to the gene. She has observed a considerable homology be- tween the gene of the rat with that of the mouse (an 80% hom- ology in introns and intergenic areas not subject to selection pressure). The regulation or altered expression of the gene for somatostatin may be of considerable importance in growth and differentiation of the embryo. Observations from the Karolinska (personal communication) suggest that this peptide hormone/transmitter is increased by alcohol and may be a major contributor to the fetal alcohol syndrome. Further, there is somatostatin in the striatum of the brain and^is not clear that it may be altered in Parkinson's Disease. Thus, an understanding of factors which might alter the expression of the gene regulating synthesis of this peptide may be of value in many areas of biology,which are of interest to CTR. DHF