IGF-I administration advances the decrease in hypersensitivity to oestradiol negative feedback inhibition of serum LH in adolescent female rhesus monkeys.

Developmental increases in serum LH were assessed in female rhesus monkeys to test the hypotheses that (1) the final stages of puberty are characterized by a decrease in hypersensitivity to oestradiol negative feedback of LH and (2) that increases in IGF-I secretion accelerate this decrease in hypersensitivity. In order to test the first hypothesis, serum LH in the absence of oestradiol and in response to three doses of oestradiol were compared between ovariectomized adult (n=6) and adolescent female monkeys (control group; n=6). The control females were not treated with oestradiol until serum LH had risen to within the 95% confidence interval of serum LH observed in ovariectomized adults. Doses of oestradiol achieved serum levels of approximately 80 («low»), 160 («intermediate»), and 250 («high») pmol/l. For control group females, treatment with the next higher dose of oestradiol was not initiated until serum LH was no longer suppressed by the lower dose. Treatment with oestradiol produced a dose-dependent suppression in serum LH in adults. In contrast, low-dose oestradiol maximally suppressed serum LH throughout the initial treatment period in the control group compared with the adult females. The low oestradiol dose effectively suppressed serum LH throughout the study period in 4/6 of the control group and became ineffective at suppressing LH after 8 months of treatment in 2/6 control group females. Initiation of the intermediate dose of oestradiol to these females again maximally suppressed LH compared with adult females. In order to determine whether IGF-I regulates this change in hypersensitivity to oestradiol negative feedback, a second group of ovariectomized, adolescent monkeys (n=6) were treated chronically with IGF-I to elevate serum IGF-I levels above those of control group females. Using the same protocol described for the control females, developmental changes in serum LH in the absence of oestradiol and in response to oestradiol negative feedback were evaluated. Treatment with IGF-I had no effect on the initial increases in serum LH occurring in the absence of oestradiol. In contrast, the decrease in hypersensitivity to the negative feedback effects of the low oestradiol dose was significantly accelerated in IGF-I-treated females, as the interval from the initiation of treatment to the point at which serum LH was no longer suppressed was shorter in IGF-I-treated (4.4±0.7 months; mean±S.E.M.) compared with control group females (8.4±1.9 months). Although none of the control group females escaped from the negative feedback effects of the intermediate dose of oestradiol during the course of the study, 2/7 of the IGF-I-treated females and so within 5.5±1.4 months of the initiation of the treatment. The present data indicate that the later stages of puberty in female monkeys are characterized by a decreasing in sensitivity to oestradiol negative feedback inhibition of serum LH and that the timing of this decrease is regulated by circulating concentrations of IGF-I. These data confirm earlier reports that the developmental increases in the GH axis accelerate the tempo of puberty without affecting its onset