Influence of estradiol on insulin-like growth factor-1-induced luteinizing hormone secretion

Abstract

Several studies suggest an interrelationship between estradiol (E 2) and insulin-like growth factor-1 (IGF-1) at the hypothalamic level. The present study was designed to discern if the capability of IGF-1 to release LH and influence the timing of female puberty is influenced by E 2. Twenty-eight-day-old female rats were ovariectomized (OVEX), then implanted with a third ventricular (3V) cannula. Two weeks later, these animals received subcutaneous (s.c.) injection of oil, or either one or two injections of E 2 in the form of estradiol benzoate (1 μg). Forty-eight hours later, four basal blood samples were drawn then the animals received IGF-1 (200 ng) or saline via the 3V and four more blood samples were taken. Results indicated that E 2 replacement lowered basal LH levels and IGF-1 induced a significant LH release in only animals that had E 2 levels above 20 pg/ml. These levels of E 2 were also associated with increases ( p<0.05) in the expression of both IGF-1 receptor (IGF-1R) mRNA and protein. In order to further support the hypothesis that the action of IGF-1 at the time of puberty is influenced by E 2, 24-day-old intact female rats received s.c. injection of sesame oil or 0.1 μg of E 2. The next day, the E 2-treated animals also received twice daily s.c. injections of either IGF-1 (500 ng) or saline until vaginal opening (VO) occurred. The animals that received E 2 plus IGF-1 showed VO at 31.1 days, which was 2.5 days earlier ( p<0.01) than E 2-treated animals and 4 days earlier ( p<0.001) than IGF-1-treated and saline control animals. Taken together, these results indicate that the hypothalamic action of IGF-1 to stimulate LH release and advance female pubertal development is dependent upon the influence of E 2.