ESPE Abstracts

Objective: In order to investigate the effect of precocity and gonadotropin-releasing hormone analogists (GnRHa) GnRHa treatment on glucose metabolism in female rats, the possible mechanism was studied through the changes of leptin, estrogen, growth hormone, insulin-like growth factor 1 and insulin receptor signal crosslinking pathway.

Methods: Forty-eight 2-day-old female Sprague-Dawley (SD) suckers were randomly divided into precocity model group and normal control group. At the age of 5 days, the model was established by subcutaneous injection of danazol. At the age of 3 weeks, 8 suckers from each group were randomly sacrificed for blood collection. The levels of leptin, estrogen, fasting blood glucose, insulin, follicle-stimulating hormone, luteinizing hormone, leptin and insulin-like growth factor 1 were measured by enzyme-linked immunosorbent assay (ELISA), and the insulin resistance index (HOMA-IR) was calculated. The remaining rats were divided into normal group, normal +GnRHa group, precocious puberty group and precocious puberty +GnRHa group. The normal +GnRHa group and precocity +GnRHa group were treated with GnRHa at 3 weeks and 5 weeks of age. At 7 weeks of age, all rats were sacrificed under anesthesia to detect the length of naso-anal and body weight, and the serological indicators were tested again. The contents of non-receptor tyrosine kinase (JAK2), insulin receptor substrate 1 (IRS1) and protein kinase B (AKT) in liver were detected by real-time PCR. The protein contents of AKT, pAKT, JAK2 and p-JAK2 were detected by Western blotting.

Results: There was no significant difference in physical development between the precocity group and the normal group at 3 weeks of age. The serum levels of luteinizing hormone (LH), follicle stimulating hormone (FSH) and insulin in the precocious puberty group were significantly higher than those in the normal group at 3 and 7 weeks of age (P <0.001). The HOMA-IR in the precocious puberty group was significantly higher than that in the normal group at 3 weeks of age (P <0.05). Sex hormones were positively correlated with HOMA-IR, p-JAK2 was an independent influencing factor of HOMA-IR, estrogen and luteinizing hormone were independent influencing factors of insulin. At 7 weeks of age, there was no significant difference in the protein contents of AKT and JAK2 among the 4 groups, but the protein contents of p-Akt and p-JAK2 were higher than those in the normal group (P <0.05). The serum indexes of GnRHa-treated precocious rats were higher than those of precocious precocious rats, and there were no significant differences in other serum indexes (including insulin) between the precocious precocious rats and the precocious precocious rats. The serum indexes of normal +GnRHa group were the lowest at 7 weeks of age.

Conclusion: Precocious puberty increased insulin level and decreased insulin sensitivity in female rats, GnRHa delayed development, but GnRHa treatment did not affect insulin sensitivity in female rats. Precocity leads to chronic activation of JAK2 and AKT in the post-receptor signaling pathway.