GROWTH HORMONE AND DIFFERENTIATION

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Pituitary growth hormone (GH) has growth promoting and differentiating effects. The relationship of these processes is poorly defined. It is not clear whether they have the same structural determinants in GH. We have a bovine GH fragment without growth promoting activity which can promote differentiation of pre-adipocytes to adipocytes. Methods have been developed to remove GH and non-GH adipogenic activity from serum. A defined medium without serum has also been developed to study both in vitro adipogenesis and growth of murine 3T3 pre-adipocytes, both responses being sensitive to GH. We shall determine if clonal expansion, terminal cell division and hormonal responsiveness that accompany pre-adipocyte differentiation are related to differentiation or require additional effects of native GH and/or other serum factors. In vivo growth promoting activity of our GH fragments will be determined in hypophysectomized rats. In vitro growth promotion by GH of pre-adipocytes will also be studied. With an adipogenic GH fragment and high vs. low frequency differentiating preadipocyte sub-clones, the nature of adipogenic receptors will be evaluated. These studies will contribute to an understanding of the mechanism of GH action and the relationship of differentiation and growth.