Effects of Growth Hormone on the Tempo of Sexual Maturation in Female Rhesus Monkeys*

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Abstract
The signal that initiates and maintains the developmental change in LHRH and, consequently, LH secretion in primates, thus regulating the tempo of puberty, is not known. Given the close association between reproductive development and bone maturation, we examined the hypothesis that GH was involved in developmental increases in LH release, specifically by augmenting the decrease in estradiol (E2) negative feedback inhibition of LH that characterizes late puberty in primates. Recombinant human GH (rhGH; 250 μg/kg) was given (sc) three times weekly to immature female rhesus monkeys to determine if developmental increases in basal serum LH would occur at an earlier age, and if menarche and first ovulation also would be advanced. The study groups included intact females receiving rhGH (INT+GH; n = 5), intact control animals (INT; n = 6), ovariectomized females receiving E2 plus rhGH (E2OVX+GH; n = 5), and E2-treated ovariectomized control monkeys (E2OVX; n = 4). The females were studied from 20 months of age until their serum LH levels increased (E2OVX groups) or until the occurrence of first ovulation (intact groups). After 12 months of rhGH treatment, the crown-rump lengths were significantly increased, regardless of ovarian status, an effect maintained in the intact females through 21 months of treatment. The mean age at the time of the initial rise in serum LH was advanced by rhGH treatment in intact females (29.6 ± 0.4 vs. 31.3 ± 0.3months), but not E2OVX females. Subsequent maturational elevations in LH secretion were similar in the E2OVX+GH and E2OVX animals even after an incremental increase in E2. Ages at menarche were similar in the INT+GH and INT groups, whereas first ovulation was significantly advanced in three of five INT+GH females (31.5 ± 0.7 months) compared to that in INT females (43.5 ± 0.3 months). The remaining INT+GH females ovulated at an age (42.4 ± 0.4 months) similar to that of INT females. Those females that ovulated by 32 months had higher skeletal maturity scores than the later ovulating INT females, with the other INT+GH females being intermediate. Furthermore, rhGH resulted in a significant increase in serum E2 levels within 12 h of injection, which remained elevated through 24 h. This effect of rhGH on ovarian E2 secretion did not occur until females had shown elevations in basal serum LH. Although rhGH did advance certain parameters of sexual maturation, the lack of higher postpubertal serum LH levels in E2OVX+GH females and the occurrence of an early first ovulation in only 60% of INT+GH females do not support the hypothesis that GH is involved in the maturation of LH release, rather GH may act synergistically with a still developing pattern of gonadotropin secretion to facilitate ovarian maturation in postmenarchial monkeys.