The overall goal is to characterize the structural variants and fragments of murine growth hormone (GH) in the pituitary gland and plasma of rats and mice. We want to test the hypothesis that GH exists in several molecular forms and that the differences seen in its actions or biological and immunological activities are mostly a consequence of this molecular heterogeneity. Although molecular heterogeneity for GH is now a well established fact in man, study of this phenomenon in animals is singularly lacking. Our goal is to develop an animal model for GH heterogeneity, so that the physio-pathological implications of this phenomenon can be investigated.
One specific aim i s to characterize the physiological significance of the murine """"""""20K"""""""" GH. Its recent detection by us in rodents and development of analytical tools makes such an investigation possible under a variety of easily manipulable experimental conditions.
A second aim i s to develop radioimmunoassay and immunoblotting assays for the murine """"""""20K"""""""" GH and some of the other GH forms recently detected by us. The ultimate goal is to correlate fluctuations in their concentrations in plasma with physiological and pathological states.
A third aim i s to characterize the physiological significance of cleaved GH in rats and mice. Cleaved human GH has greater growth-promoting and lactogenic activities than intact human GH. Furthermore, it binds more readily to hepatic receptors, suggesting that it may have important biological functions. Our recent work shows the occurrence of cleaved GH in murine pituitary extracts and in human plasma.
A fourth aim i s to study the physiological significance of the newly-observed 12,000 dalton pituitary peptide with partial structural resemblance to GH, the possible glycosylated GH, and the oligomeric forms of GH detected by immunoblotting. One- and two-dimensional electrophoresis in basic and SDS gels and peptide mapping will be used to identify the various forms. Physiological studies will be carried out in rats and mice. Isolations will be carried out by electroelution from gels and by HPLC, Sephadex, and DEAE-cellulose chromatography. Radioimmunoassay and immunoblotting assays will be developed by standard procedures. The study will help in understanding GH-related disorders.
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