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

• Published in: Journal of endocrinology Vol. 166; no. 2; pp. 283 - 291
• Main Authors: Gonzalez, C, Alonso, A, Alvarez, N, Diaz, F, Martinez, M, Fernandez, S, Patterson, AM
• Format: Journal Article
• Language: English
• Published: England BioScientifica 01.08.2000
• Subjects: Analysis of Variance; Animals; Blood Glucose - analysis; Body Weight - drug effects; Drug Synergism; Estradiol - pharmacology; Female; Glucose - pharmacology; Glucose Clamp Technique; Insulin - metabolism; Insulin Resistance; Ovariectomy; Pregnancy; Progesterone - pharmacology; Random Allocation; Rats; Rats, Wistar
• ISSN: 0022-0795; 1479-6805
• DOI: 10.1677/joe.0.1660283

The mechanism for the development of insulin resistance in normal pregnancy is complex and is associated with serum levels of both progesterone and 17beta-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 17beta-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 17beta-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 17beta-estradiol (E)- and 17beta-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 17beta-estradiol and progesterone are low, could be due to 17beta-estradiol. However, during late pregnancy when the plasma concentrations of 17beta-estradiol and progesterone are high, the role of 17beta-estradiol could be to antagonize the effect of progesterone, diminishing insulin sensitivity.