Growth and development.

GH acts chronically on adipocytes to inhibit lipogenesis, antagonise insulin action and accentuate lipolysis. In addition, in some species, but not sheep, GH has a transient, acute, insulin-like effect, while for some preadipocyte-like cell-lines GH acts as a commitment factor. Studies on GH signalling in adipocytes have focused on these latter two effects and have implicated STAT proteins, MAP kinase, phosphatidylinositol3 kinase (PI3K) and p70s6 kinase. Explants of sheep adipose tissue respond chronically to GH in vitro, and have been used to show that the GH-induced inhibition of lipogenesis is due in part to a decreased transcription of acetyl CoA carboxylase, while the accentuation of lipolysis by GH is due partly to a decreased ability of adenosine to inhibit catecholamine-stimulated lipolysis. Effects of GH on lipogenesis and response to adenosine are prevented by actinomycin D, an inhibitor of gene transcription, and H7, an inhibitor of protein serine kinases. However, inhibitors of MAP kinase and p70s6 kinase did not prevent effects of GH, and GH did not activate MAP kinase in sheep adipocytes. Wortmanin, an inhibitor of PI3K mimicked the effects of GH on both lipogenesis and response to adenosine. The phorbol ester, PMA, which activates and then down-regulates some isoforms of protein kinase C (PKC) partly inhibited effects of GH on lipogenesis and mimicked GH effects on response to adenosine. The PKC isoforms involved were determined using differentiated 3T3-F442A adipocytes. Individual PKC isoforms were eliminated using antisense techniques. Loss of either PKCα, δ, or zeta had no effect on the inhibition of lipogenesis by GH, elimination of either PKC γ or μ partly decreased the effect of GH while removal of both diminished the inhibitory effects of GH by 80%. Thus the chronic metabolic effects of GH involve both gene transcription and involvement of isoforms of PKC, whereas the MAP kinase and PI3K pathways do not appear to be involved.