Carbohydrate metabolism of female rat adipocytes: effects and mechanisms of action of progesterone

This short review describes the role of progesterone in the insulin-resistance of pregnancy and the present knowledge of the intracellular mechanisms of action of the steroid in carbohydrate metabolism of female rat adipocytes. Observations concerning steroid effects on the binding of insulin to its specific receptors are often contradictory, and depend on cells used to study it. It is now generally accepted that, in isolated adipocytes, the decreased responsiveness to insulin produced by progesterone is due to a post-receptor effect. Furthermore, basal glucose metabolism (in the absence of insulin) is decreased by progesterone treatment and by the acute effect of progesterone when added directly into the incubation medium. Progesterone induces an intrinsic post-receptor effect which is related to decreased phosphorylation of glucose by hexokinase but has no effect on glucose transport. The effect on hexokinase activity is an indirect one taking place either before or after activation of the enzyme. During the last decade, a large body of evidence (Xenopus oocytes and other cells) indicates that steroids interact with the cell surface rather than penetrating the cell and interacting exclusively with a nuclear receptor. The second messengers, such as cyclic AMP and calcium, play a major role in this non-genomic mechanism. The direct and rapid effect (20 min.) of progesterone in adipocytes supports the non-genomic mechanism of action; there is neither any lag period prior to the appearance of the physiological response nor any inhibition of protein synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)