ence. Preliminary studies suggest that certain of 
these exchanges result in an exchange in transla- 
tional efficiencies. These investigations are being 
pursued to characterize further the structure(s) 
and mode(s) of action of the translational control 
determinant(s). 
III. Interactions of mRNA Secondary Structure with 
the Translational System. 
In previous studies this laboratory demonstrated 
that the elongating 80 S ribosome can melt out ex- 
tensive duplexes formed between mRNA and cDNA. 
This may reflect the ability of the ribosome to un- 
wind mRNA secondary structure during translation. 
This assumption is being tested directly. Site-spe- 
cific secondary structures are being introduced into 
mRNAs, and their effects on translation are being 
monitored. Intramolecular duplexes are being posi- 
tioned at specific regions within the mRNA to deter- 
mine whether the proposed RNA helicase activity is 
present and whether it is dependent on active 
translation. The effects of the translational system 
on the stability of mRNA duplexes, and the recipro- 
cal effiect of such duplexes on translational effi- 
ciency, are being studied as critical components in 
the dynamic interactions that determine the com- 
partmentalization, stability, and translational effi- 
ciencies of an mRNA. 
IV Expression and Function of the Human Growth 
Hormone Genes. 
In collaboration with Dr. Nancy Cooke (Univer- 
sity of Pennsylvania), this laboratory is also studying 
the expression and function of the human grov^h 
hormone genes. There are five functional genes in 
humans that encode the growth hormone-prolac- 
tin family of hormones: hGH-N; two placentally 
expressed chorionic somatomammotropin genes 
PUBLICATIONS 
(hCS-A and hCS-B); hGH-V; and prolactin (hPRL). 
The encoded proteins are responsible for determin- 
ing a number of functions critical to groviT:h and re- 
production. 
Studies in this laboratory have defined the hGH- 
V gene as a placental growth hormone. This gene is 
expressed in the syncytiotrophoblastic epithelium 
of the villi, and the level of expression increases 
dramatically during gestation. Unlike the closely 
related pituitary growth hormone, hGH-V is ex- 
pressed as an N-linked glycoprotein. Ongoing stud- 
ies are attempting to define the function(s) of this 
protein by characterizing its pattern of receptor 
binding activity. The biological activities of the GH- 
PRL family of hormones are mediated by selective 
binding to two classes of membrane receptors, 
somatogen and lactogen. Primate growth hormones 
such as hGH-N are unusual, in that they bind to 
both classes of receptors. By using conditioned 
media from cells stably transformed with the hGH- 
V gene as a source of hGH-V it has been possible to 
demonstrate that hGH-V is also able to bind to 
both receptor classes. Of additional interest, com- 
parison of the relative binding affinities of hGH-N 
and hGH-V to somatogen and lactogen receptors 
demonstrates that hGH-V may be sevenfold more 
somatogenic than hGH-N. This finding, along with 
results from other laboratories, suggests that the 
hGH-V may be a gestational growth hormone of im- 
portance in the growth of the fetus and/or the met- 
abolic regulation in the mother. Site-specific muta- 
tions within the hGH-V and hGH-N genes that alter 
a variety of the 13-amino acid differences between 
them should allow a more detailed understanding 
of the structural basis for their different receptor 
binding profiles. 
Dr. Liebhaber is also Associate Professor of 
Human Genetics and Medicine at the University of 
Pennsylvania School of Medicine. 
Books and Chapters of Books 
Liebhaber, S.A. 1988. Use of in vitro translation techniques to study gene expression. In Methods in Hema- 
tology (Benz, E.J. , Jr., Ed.). Edinburgh: Churchill Livingstone, pp 169-180. 
Articles 
Albitar, M., Peschle, C, and Liebhaber, S.A. 1989. Theta, zeta, and epsilon globin messenger RNAs are ex- 
pressed in adults. Blood 74:629-637. 
Continued 
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