MATURATIONAL ROLES OF GONADOTROPIN RELEASING HORMONE (GNRH) PULSE FREQUENCY

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Puberty represents a time of complex changes in hormone secretion. The purpose of this research is to better understand how the hormone changes of puberty happen. A better understanding of these changes may result in earlier diagnosis and treatment of pubertal disorders. Recent data indicate that boys and 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 may be regulated by changes in the recently discovered gonadal peptides, activin, inhibin and follistatin. In this research, novel assays and experimental treatments will be employed to investigate the mechanisms of puberty in girls as compared to boys, testing the hypothesis that gonadotropin secretion in girls is altered in response to the changing ovarian sex steroid and ovarian peptide milieu. As puberty progresses, we believe that gonadotropin secretion is less regulated by brain neurotransmitters while gonadal peptides and sex steroids develop a more prominent role in regulating gonadotropin secretion in the pituitary gland. In this research we will: 1) determine the role of estradiol and/or progesterone in the development of opioid inhibition of GnRH secretion using sex steroid replacement studies; 2) relate changes in serum inhibin A and B, activin A, and follistatin concentrations to serum gonadotropin and sex steroid concentrations throughout childhood and puberty; and 3) relate serum sex steroid and gonadal peptide concentrations to serum FSH concentrations during early and late puberty conditions. 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.