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Estradiol Negative Feedback Regulates Nocturnal Luteinizing Hormone and Follicle-Stimulating Hormone Secretion in Prepubertal Female Rhesus Monkeys

Division of Psychobiology, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia 30322

Address all correspondence and requests for reprints to: Mark E. Wilson, Yerkes National Primate Research Center, Emory University, 954 Gatewood Road, Atlanta, Georgia 30329. E-mail: markw{at}rmy.emory.edu.

In recent years, animal models of puberty in children have focused on factors responsible for the developmental increase in gonadotropin secretion independent of gonadal negative feedback. Although the testis may play little if any role in timing the initial increase in gonadotropin secretion in the male, the situation may be different for the female. The present study tested the hypothesis that removal of endogenous estradiol by ovariectomy would produce an immediate increase in nocturnal but not daytime LH and FSH concentrations, an effect reversed by estradiol replacement. Morning (1000 and 1030 h) and evening (2200 and 2230 h) concentrations of bioactive LH and, in selected samples, immunoreactive FSH were evaluated in young juvenile female rhesus monkeys (n = 7) before and after ovariectomy at 13 months of age. Evening but not morning concentrations of gonadotropins were significantly increased within 2 wk of ovariectomy, whereas estradiol replacement returned these to presurgical levels and to those observed in age-matched, gonadally intact females (n = 7). By 145 d after ovariectomy, or approximately 17 months of age, evening as well as morning concentrations of LH were significantly higher than concentrations seen immediately after surgery. Estradiol replacement at approximately 18 months of age suppressed both morning and evening LH but not to the degree seen during a similar treatment after ovariectomy. These data support the hypothesis that, for the female, the developmental rise in diurnal gonadotropin secretion is controlled by a gonad-independent mechanism as well as a gonadal negative feedback inhibition. The importance of gonadal restraint on gonadotropin secretion in young juvenile females is evident only in samples obtained during the evening. These data underscore the notion that, for the female puberty, onset, at least in terms of gonadotropin secretion, is a misnomer and that puberty reflects a progression in multiple control mechanisms that ultimately time the attainment of fertility.

This work was supported by NIH Grant HD37583 and, in part, Grant RR00165.

Abbreviations: CV, Coefficient(s) of variation; INT, gonadally intact; OVX, ovariectomized.