CONSTANT LOW-DOSE ESTRADIOL REPLACEMENT ACCELERATES SKELETAL MATURATION AND GROWTH IN OVARIECTOMIZED ADOLESCENT RHESUS-MONKEYS

The effects of oestradiol (OE2) on adolescent growth in female rhesus monkeys were evaluated by testing the hypothesis that, upon removal of the ovary, the increase in growth normally seen at the time of pubert y would be abolished and that treatment with OE2 would restore it. Juv enile monkeys (n = 12) were ovariectomized and were given either an OE 2-bearing silicone elastomer capsule implanted subcutaneously to simul ate mid-pubertal concentrations ('treated =', n=8) or no steroid treat ment ('control =', n = 4). Females were studied from 18 to 42 months o f age which, in intact females, typically encompasses the prepubertal period to the occurrence of first ovulation. Over the whole period, gr owth in body weight, crown-rump (CR) length and tibia length for contr ol females were less than the 95% confidence limits of females treated with OE2. However, significant spurts of growth in both CR and tibia length occurred in the control as well as treated animals, although th e peak velocities were somewhat lower for non-OE2-treated animals. Pea k growth velocities occurred at an earlier chronological age in treate d females, although at the same degree of skeletal maturity as found i n control females. Skeletal maturity was significantly advanced in tre ated females from 27 months onward. Serum concentrations of nocturnal GH increased significantly with advancing age in both groups, with gre ater increases observed in treated females. Serum concentrations of IG F-I were higher in treated females until some 30 months of age, at whi ch point concentrations increased in a similar fashion in both groups. IGF-I concentrations were elevated in the months preceding and follow ing the peak CR growth velocity in treated females whereas concentrati ons of IGF-I rose coincidently with peak CR growth in control females. These data indicate that, in the absence of OE2, growth in female mon keys has periods of acceleration and that OE2 may enhance this pre-set pattern. Furthermore, the growth-promoting effects of OE2 are determi ned by the degree of skeletal maturity. Once a certain degree of skele tal maturity is attained, bones may be primed for maximal growth, but, as skeletal maturity continues to advance, the effect of OE2 on growt h diminishes.