Studies in Patients with Congenital GnRH Deficiency

先天性 GnRH 缺乏症患者的研究

• 批准号: 10696795
• 负责人: Janet Hall
• 金额: $ 4.9万
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10696795
• 关键词: Address; Anosmia; Clinical; Development; Diagnosis; Disease; Estradiol; Failure; Female; Fertility; Functional disorder; General Hospitals; Genetic; Genotype; Gonadotropin Hormone Releasing Hormone; Gonadotropins; Hospitals; Hypothalamic structure; Idiopathic Hypogonadotropic Hypogonadism; Incidence; Inherited; Kallmann Syndrome; Klinefelter' s Syndrome; Massachusetts; Modeling; Molecular; Neurosecretory Systems; Patients; Phenotype; Physiologic pulse; Physiological; Pituitary Gland; Protocols documentation; Puberty; Rare Diseases; Regimen; Regulation; Reproduction; Reproductive Physiology; Research Personnel; Role; Smell Perception; Testosterone; Woman; hormone deficiency; interest; male; men; reproductive function; reproductive system disorder

In this study we are performing phenotype/genotype studies in males and women with congenital deficiency in the secretion or responsiveness to gonadotropin releasing hormone (GnRH). Isolated GnRH deficiency is a rare disorder, with an estimated incidence of 1/50,000. Patients present with failure of normal pubertal development and hypogonadotropic hypogonadism (low LH, FSH and estradiol or testosterone), indicative of a hypothalamic or, less frequently, pituitary abnormality. The disorder is referred to as isolated hypogonadotropic hypogonadism (IHH). Approximately 50% of these patients lack a sense of smell (Kallmann Syndrome, KS) while the other half are normosmic (nIHH). Studies in KS/nIHH patients have been particularly informative in helping us understand the GnRH requirements for normal reproductive function and have led to development of a physiologic regimen of GnRH replacement in men and women. While pulsatile GnRH serves as treatment for patients interested in conceiving or in their potential to conceive, these patients have provided a clinical model that allows us to address key questions in reproductive physiology. Our currently active protocols focus on further understanding the genetic underpinnings of GnRH deficiency, understanding the full phenotype of the spectrum of patients who present with GnRH deficiency and understanding the genotype/phenotype correlations in this disorder. This study is being conducted in patients identified by the PI with the support of investigators at Massachusetts General Hospital and St Jude's Hospital as is part of the PIs long-term collaborative efforts.

在这项研究中，我们对先天性促性腺激素释放激素 (GnRH) 分泌或反应缺陷的男性和女性进行表型/基因型研究。 孤立性 GnRH 缺乏症是一种罕见疾病，估计发病率为 1/50,000。患这种疾病被称为孤立性低促性腺激素性性腺功能减退症（IHH）。这些患者中大约 50% 缺乏嗅觉（卡尔曼综合症，KS），而另一半则嗅觉正常（nIHH）。对 KS/nIHH 患者的研究在帮助我们了解正常生殖功能的 GnRH 需求方面提供了特别丰富的信息，并导致了男性和女性 GnRH 替代生理方案的开发。虽然脉冲式 GnRH 可作为对怀孕或有怀孕潜力的患者的治疗方法，但这些患者提供了一个临床模型，使我们能够解决生殖生理学中的关键问题。我们目前正在进行的方案重点是进一步了解 GnRH 缺乏症的遗传基础，了解 GnRH 缺乏症患者的完整表型，并了解这种疾病的基因型/表型相关性。 这项研究是在马萨诸塞州总医院和圣裘德医院研究人员的支持下，在 PI 确定的患者中进行的，这是 PI 长期合作努力的一部分。