MATURATIONAL ROLES OF GONADOTROPIN RELEASING HORMONE (GNRH) PULSE FREQUENCY

青春期是激素分泌发生复杂变化的时期。这项研究的目的是为了更好地了解青春期激素的变化是如何发生的。更好地了解这些变化可能会导致早期诊断和治疗青春期障碍。最近的数据表明，男孩和女孩在青春期促性腺激素分泌方面存在差异。与男孩相比，女孩的黄体生成素分泌对性类固醇反馈的反应似乎有所不同，儿童时期女孩的卵泡刺激素浓度受到的抑制相对较少。促性腺激素可能受最近发现的性腺肽、激活素、抑制素和卵泡抑素变化的调节。在这项研究中，将采用新的检测方法和实验治疗方法来研究女孩与男孩相比青春期的机制，验证女孩的促性腺激素分泌随着卵巢性类固醇和卵巢肽环境的变化而改变的假设。随着青春期的发展，我们认为脑神经递质对促性腺激素分泌的调节越来越少，而性腺肽和性类固醇对垂体促性腺激素分泌的调节作用越来越突出。在这项研究中，我们将：1)通过性类固醇替代研究确定雌二醇和/或孕酮在阿片类药物抑制GnRH分泌的发展中的作用；2)儿童期和青春期血清抑制素A和B、激活素A和卵泡抑素浓度变化与血清促性腺激素和性类固醇浓度的关系；3)将青春期早期和晚期的血清性类固醇和性腺肽浓度与血清FSH浓度联系起来。青春期导致生殖激素的神经内分泌控制发生显著变化，研究这些变化有助于更好地理解生殖异常和不孕症的病理生理学。

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.