[Insulin resistance enhanced the response of the ovary]

To search for the role of impaired insulin signaling in the ovary reproductive failure and abnormal metabolic profiles in the AKT2- mouse.

Adult, female 129/C57BL/6 (AKT2-) mice were used in these studies. Littermate wide types C57BL/6J (AKT2+), as well as mutant genotypes (AKT2-). The ovaries were abstained from 6 AKT2+ type mice as wall as 6 mutant genotypes, which was used for insulin stimulated glucose uptake study. By ovary transplantation on the day of 12 weeks, three genotypic mice were constructed with body AKT2+ and ovary AKT2+ in Group A, body AKT2+ and ovary AKT2- in Group B, body AKT2- and ovary AKT2+ in Group C. The vaginal smear was done to evaluate the recovery and cyclicity of transplanted ovaries with mutant or intact AKT2. Before execution, every group was randomly separated into basal and stimulated groups in which the mice were injected recombination FSH (0.75 IU/g), and then AKT2, GSK3beta, ERK-1, CYP17 and CYP19 were determined by RT-PCR in the ovaries, and the serum were reserved for the assay of HDL-C, CHO, TG, 17-OHP progesterone, E(2), T, and LH. The weight of each mouse, their ovary and their fat pads and the estrus cycle, were also recorded.

(1) The weight of fat pads beside ovaries and fold inguen in C group were significant higher than the other groups. (2) The level of 17-OHP progesterone in B group was higher than A or C group both in basal and FSH-stimulated groups. (3) In the basal group the expression of ERK-1 and CYP17 were enhanced. Moreover in FSH-d stimulated group, the expression of ERK-1, CYP17, CYP19 and GSK3B in B group were higher as compared with the other groups.

(1) IR existed in the ovary of AKT2- type, and the mice with AKT2-type ovary had delayed cycle, PCO and high level of 17-OHP, which were similar with PCOS. (2) Metabolic dysfunction in the AKT2- mice has close relationship with whole body condition, but not defective insulin signal within ovaries. (3) Defects of insulin activity in the metabolic pathway could induce the increased expression of ERK-1 and mitogenic potential indicating the cross-talk between two pathways of insulin signaling within ovarian cells. Consequently, ovarian hyperovarianism was induced in the defective ovaries, which contribute to the enhanced response to gonadotropin and synthesis of steroid hormone.