The Regulatory Effect of Insulin-Like Growth Factor-2 on Hypothalamic Gonadotropin-Releasing Hormone Neurons during the Pubertal Period.

Abstract

Background: The insulin-like growth factor (IGF) system plays a vital role in regulating gonadotropin-releasing hormone (GnRH), whether the IGF2 can act on the GnRH neurons during the pubertal period is unclear.

Methods: Central precocious puberty (CPP) rats were induced by danazol, and when the rats met the first diestrus, they were euthanized and tissues were collected. GT1-7 cells were cultured and treated with 0, 1, 10 ng/mL IGF2 for 4 hours and the changes in GnRH were measured. Mice were injected intracerebroventricularly with IGF2 (15 ng/g, 5 μL) or with the same dose of phosphate buffered saline (PBS), after eight hours, they were euthanized and tissues collected.

Results: CPP rats had increased expression of IGF2 and GnRH mRNA and their respective proteins in the preoptic area (POA) of the hypothalamus. Treatment of GT1-7 cells with 10 ng/mL of IGF2 increased GnRH mRNA and protein expression, and GnRH concentration in the culture medium. Injection of IGF2 protein into the lateral ventricle of mice increased the expression of GnRH mRNA and protein in the POA.

Conclusions: IGF2 may upregulate the synthesis of GnRH during the pubertal period, and may also take part in the pathology of CPP.