Vernon R G
Hannah Research Institute, Ay, UK.
J Endocrinol. 1996 Jul;150(1):129-40. doi: 10.1677/joe.0.1500129.
The intracellular signalling systems involved in the chronic insulin-antagonistic, anti-lipogenic effects and also the lipolytic effect of GH have been investigated in sheep adipose tissue in an in vitro tissue culture system. During culture, chronic exposure to GH decreased the rate of lipogenesis and prevented the increase in lipogenesis induced by insulin. GH also increased glycerol release into the culture medium. GH had no acute, insulin-like effect on lipogenesis in sheep adipose tissue. Pretreatment with phorbol ester to down-regulate isoforms of protein kinase C or addition of the protein serine kinase inhibitor staurosporine decreased the anti-lipogenic effect of GH while the protein serine kinase inhibitor H7 eliminated it completely. Pretreatment with phorbol ester or addition of H7 also decreased the insulin-antagonistic effect of GH on lipogenesis. Addition of the protein serine phosphatase inhibitor okadaic acid or the phosphatidyl choline phospholipase C inhibitor D609 both diminished the anti-lipogenic and insulin-antagonistic effects of GH. Chronic exposure of adipose tissue to GH had no effect on the total activity of acetyl CoA carboxylase or its activation status but it did diminish the increase in activation status induced by insulin. H7 and okadaic acid also diminished the increase in activation status of acetyl CoA carboxylase induced by insulin but did not alter the effect of GH on this variable. Okadaic acid decreased total acetyl CoA carboxylase activity. Pretreatment with phorbol ester or the addition of H7, staurosporine or okadaic acid increased glycerol release into the culture medium to the same extent as GH itself; the effects of GH and these various agents were not additive. These studies suggest that the anti-lipogenic, insulin-antagonistic effects of GH involve both protein serine kinases and phosphatases, possibly including one or more isoforms of protein kinase C, and a phosphatidyl choline-specific phospholipase C. Comparison with studies by others on the GH enhancement of preadipocyte differentiation and prolactin stimulation of lipogenesis in mammary tissue suggests involvement of protein kinase C at an early stage in all three systems. In contrast, effects of okadaic acid vary with the system, suggesting the involvement of protein serine phosphatase activity in a late stage of the action of GH. The effects of GH on lipogenesis and lipolysis do not occur via identical mechanisms.
在体外组织培养系统中，对绵羊脂肪组织中涉及生长激素（GH）的慢性胰岛素拮抗、抗脂肪生成作用以及脂解作用的细胞内信号传导系统进行了研究。在培养过程中，长期暴露于GH会降低脂肪生成速率，并阻止胰岛素诱导的脂肪生成增加。GH还会增加甘油释放到培养基中。GH对绵羊脂肪组织的脂肪生成没有急性胰岛素样作用。用佛波酯预处理以下调蛋白激酶C的同工型或添加蛋白丝氨酸激酶抑制剂星形孢菌素会降低GH的抗脂肪生成作用，而蛋白丝氨酸激酶抑制剂H7则可完全消除该作用。用佛波酯预处理或添加H7也会降低GH对脂肪生成的胰岛素拮抗作用。添加蛋白丝氨酸磷酸酶抑制剂冈田酸或磷脂酰胆碱磷脂酶C抑制剂D609都会减弱GH的抗脂肪生成和胰岛素拮抗作用。脂肪组织长期暴露于GH对乙酰辅酶A羧化酶的总活性或其激活状态没有影响，但确实减弱了胰岛素诱导的激活状态增加。H7和冈田酸也减弱了胰岛素诱导的乙酰辅酶A羧化酶激活状态的增加，但没有改变GH对该变量的影响。冈田酸降低了乙酰辅酶A羧化酶的总活性。用佛波酯预处理或添加H7、星形孢菌素或冈田酸会使甘油释放到培养基中的程度与GH本身相同；GH和这些不同试剂的作用没有相加性。这些研究表明，GH的抗脂肪生成、胰岛素拮抗作用涉及蛋白丝氨酸激酶和磷酸酶，可能包括蛋白激酶C的一种或多种同工型，以及一种磷脂酰胆碱特异性磷脂酶C。与其他人关于GH增强前脂肪细胞分化和催乳素刺激乳腺组织脂肪生成的研究相比，表明蛋白激酶C在所有这三个系统的早期阶段都有参与。相反，冈田酸的作用因系统而异，表明蛋白丝氨酸磷酸酶活性参与了GH作用的后期阶段。GH对脂肪生成和脂解的作用并非通过相同机制发生。
