The mechanism for the development of insulin resistance in normal pregnancy is complex and is associated with serum levels of both progesterone and 17 -estradiol. However, it remains unclear whether estrogens alone or progestins alone can cause insulin resistance, or whether it is a combination of both which produces this effect. We attempted to determine the role played by progesterone and/or 17 -estradiol on the phenomena of sensitivity to insulin action that take place during pregnancy in the rat. Ovariectomized rats were treated with different doses of progesterone and/or 17 -estradiol in order to simulate the plasma levels in normal pregnant rats. A euglycemic/ hyperinsulinemic clamp was used to measure insulin sensitivity. At days 6 and 11, vehicle (V)-and progesterone (P)-treated groups were more insulin resistant than 17 -estradiol (E)-and 17 -estradiol+progesterone (EP)-treated groups. Nevertheless, at day 16, the V, EP and E groups were more resistant to insulin action than the P group. On the other hand, the V, EP and E groups were more insulin resistant at day 16 than at day 6, whereas the P group was more insulin resistant at day 6 than at day 16. Our results seem to suggest that the absence of female steroid hormones gives rise to a decreased insulin sensitivity. The rise in insulin sensitivity during early pregnancy, when the plasma concentrations of 17 -estradiol and progesterone are low, could be due to 17 -estradiol. However, during late pregnancy when the plasma concentrations of 17 -estradiol and progesterone are high, the role of 17 -estradiol could be to antagonize the effect of progesterone, diminishing insulin sensitivity.

Mammary glands, besides being among the tissues in the body with the highest lipid content after adipose tissue (1), are one of the most active metabolic tissues in the body during pregnancy and lactation. Milk lipid is an important source of both calories and essential fatty acids for the newborn. During lactation, women secrete 800 ml of milk per day containing 4% fat, mostly corresponding to triacylglycerols, of which the mammary gland synthesizes ‫ف‬ 32 g daily (2). The lactating mouse mammary gland secretes 5 ml of milk per day containing ‫ف‬ 30% fat (3). To develop this transitory capacity for handling such a large amount of lipids, the morphology of the mammary tissue changes during pregnancy and lactation. In nonpregnant mammary glands, the predominant cells are adipocytes with epithelial structures interdispersed among them. During pregnancy, in mammary glands there is an extensive proliferation of alveolar structures into the adipocytes, accompanied by differentiation of epithelial cells (4), which show cytoplasmic lipid droplets (5) surrounded by the protein adipophilin (6). During lactation, epithelial cells are the predominant cell type, and only small channels of lipid-filled adipocytes and lipid-depleted adipocytes may be distinguished.During pregnancy, major changes in maternal lipid metabolism occur. Fat depots accumulate during the early stages of pregnancy and decrease during the late phases (7). Net catabolic changes taking place in adipose tissue during late pregnancy are manifested by an enhanced hormone-sensitive lipase (HSL) activity and decreased LPL activity (8), which result in an increase in maternal plasma lipids both in humans (9, 10) and in rats (11,12). The increments of triglyceride (TG)-rich lipoproteins (chylomicrons and VLDLs) are among the most pronounced changes in plasma lipids during late pregnancy (10,13,14). Reduced adipose tissue LPL activity during late gestation allows blood TG to be diverted from storage in adipose tissue to other tissues, such as mammary glands, where there is an induction in LPL expression and activity, allowing the subsequent hydrolysis and uptake of circulating TG in preparation for lactation (15,16).