Despite extensive investigation of the hormonal changes underlying the pubertal transition, may questions remain regarding how the restrained pattern of childhood gonadotropin secretion increased in the face of rising sex steroid concentrations to exhibit the variable patterns of adulthood that support menstrual cyclicity and ovulation. Recent data indicate that boys have girls have differences in pubertal gonadotropin secretion. LH secretion appears to respond differently to sex steroid feedback in girls compared to boys, and FSH concentrations are relatively less suppressed in childhood in girls than in boys. The gonadotropins, and particularly FSH, may be regulated in changes in the gonadal peptides, activin, inhibin and follistatin. Exploration of the roles of these peptides in regulation of gonadotropin secretion has been hampered until now by lack of specific assays. In this research, novel assays and experimental treatments will be employed to investigate the mechanisms of puberty in girls, testing the hypothesis that gonadotropin secretion in girls is altered in response to the changing ovarian sex steroid and ovarian peptide milieu. Specifically, it is hypothesized that, during puberty there is a switch in the neuroendocrine responses to sex steroid feedback involving changes in opioid tone and a more predominant role of the pituitary. It is also hypothesized that FSH secretion is progressively inhibited by the developing gonad's increasing secretion of inhibition and follistatin. The hypothesis will be evaluated by examining the interactions of LH, FSH and the ovarian secretions, estradiol inhibin A and B, and follistatin, during puberty in girls: 1) determining the role of estradiol and/or progesterone in the development of opioid inhibition of GnRH secretion using sex steroid replacement studies; 2) examining the changes in hypothalamic and pituitary sensitivity to estradiol between adult women and pubertal girls; 3) relating changes in serum inhibin A and B, activin A, and follistatin concentrations to serum gonadotropin and sex steroid concentrations to serum FSH concentrations during gonadotropin- dependent and independent precocious puberty in girls. Puberty results in remarkable changes in the neuroendocrine control of the reproductive hormones, and study of these changes should lead to a better understanding of the pathophysiology of reproductive abnormalities and infertility.
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