Role of 17beta-estradiol and/or progesterone on insulin sensitivity in the rat: implications during pregnancy

Abstract

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.

Acute effects of 17β-estradiol and genistein on insulin sensitivity and spatial memory in aged ovariectomized female rats

“…Our results confirm that aging results in a significant increase in the basal levels of glucose, a fact that is exacerbated by ovariectomy. Moreover, as we expected, 1 h of estradiol treatment was enough to improve this parameter, a good evidence suggesting rapid or nongenomic actions of estrogen, as we previously showed (Alonso et al 2006a(Alonso et al ,b, 2008Gonzalez et al 2000, ) and estradiol-treated (E, ) and genisteintreated (G1, and G2, ) rats. Mean±SEM for seven animals.…”

“…Clamp experiments were performed in anesthetized rats using a previously described procedure (Alonso et al 2006a(Alonso et al , 2008Gonzalez et al 2000). After 12 h of fasting, animals were anesthetized with sodium pentobarbital (50 mg/kg), and the left saphenous vein was catheterized for insulin and glucose infusion.…”

“…However, the mechanism underlying the increase in insulin resistance with advanced age remains unclear, although it seems to be related in females to a decrease in estrogen plasma levels. In spite of this, previous studies (Gonzalez et al 2000(Gonzalez et al , 2002(Gonzalez et al , 2003 and several clinical observations (Kumagai et al 1993;Polderman et al 1994) not only suggest an interaction between insulin and sex hormones, but also demonstrate that estrogen replacement therapy improves insulin sensitivity in postmenopausal women (Colacurci et al 1998;Karjalainen et al 2001) and rodents (Alonso et al 2006a(Alonso et al , 2008.…”

Chronic 17β-estradiol treatment improves skeletal muscle insulin signaling pathway components in insulin resistance associated with aging

“…Clamp experiments were performed using a previously described procedure (González et al 2000), the results of which were published recently (Alonso et al 2006). Before and after the clamp study, blood samples for the determination of insulin and 17β-estradiol plasma concentrations were collected from the jugular vein into heparinized tubes, centrifuged at 3,000 rpm for 20 min at 4°C and plasma was immediately drawn off and stored frozen at −20°C until assayed.…”

“…Experimental studies (González et al 2000(González et al , 2003Kumagai et al 1993) and clinical observations (Colacurci et al 1998;Karjalainen et al 2001) have demonstrated the importance of estrogen in the maintenance of insulin sensitivity in postmenopausal women. However, the route, dose and type of estrogen used appear to determine the efficacy of therapy.…”