Role of 17beta-estradiol and/or progesterone on insulin sensitivity in the rat: implications during pregnancy.
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.
González
C
C
Departamento de Biología Funcional (Fisiología), Facultad de Medicina, Universidad de Oviedo, Oviedo, Spain. tinog@correo.uniovi.es
Alonso
A
A
Alvarez
N
N
Díaz
F
F
Martínez
M
M
Fernández
S
S
Patterson
A M
AM
D000704:Analysis of Variance; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D004357:Drug Synergism; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005947:Glucose / Q000494:pharmacology; D015309:Glucose Clamp Technique; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D010052:Ovariectomy; D011247:Pregnancy; D011374:Progesterone / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
D001786:Blood Glucose; D007328:Insulin; D011374:Progesterone; D004958:Estradiol; D005947:Glucose