Cytokine Modulation by Follicle-Stimulating Hormone

卵泡刺激激素调节细胞因子

• 批准号: 7230050
• 负责人: JOSEPH G CANNON
• 金额: $ 15.1万
• 依托单位: AUGUSTA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7230050
• 关键词: Affect; Aging; Applications Grants; Area; Attention; Biological; Blood Vessels; Bone Density; Bone Resorption; Cardiovascular Diseases; Cell membrane; Cells; Condition; Cultured Cells; Cytokine Receptors; Data; Development; Dose; End Point; Enzyme-Linked Immunosorbent Assay; Estradiol; Estrogens; Event; Flow Cytometry; Follicle Stimulating Hormone; Follicle Stimulating Hormone Receptor; Gonadotropins; Health; Hormone replacement therapy; Human; Hypothalamic structure; Inflammatory; Interleukin 6 Receptor; Interleukin-1; Interleukin-6; Interleukins; Investigation; Lead; Lesion; Leukocytes; Life; Longitudinal Studies; Luteinizing Hormone; Lymphocyte; Measures; Medial; Mediating; Mediator of activation protein; Menopause; N-telopeptide; Osteocalcin; Osteoporosis; Ovarian; Parathyroid Hormones; Perimenopause; Peripheral Blood Mononuclear Cell; Physiologic pulse; Plasma; Population; Postmenopause; Production; Progesterone; Pulse taking; Reagent; Regulation; Research Project Grants; Risk; Risk Factors; Roentgen Rays; Serum; Skeletal system; Staging; Steroids; TNF gene; Testing; Thick; Tumor Necrosis Factor-alpha; Tumor Necrosis Factors; Ultrasonography; Woman; base; bone turnover; cytokine; human PTH protein; human TNF protein; indexing; monocyte; neutrophil; peripheral blood; proliferative phase Menstrual cycle; receptor; response; steroid hormone

DESCRIPTION (provided by applicant): The menopausal transition involves dramatic decreases in circulating ovarian steroids and dramatic increases in circulating hypothalamic gonadotropins. The biological consequences of estrogen loss on health problems associated with aging and menopause, such as osteoporosis and cardiovascular disease, have been studied extensively. 1 consequence is that tonic inhibition of inflammatory cytokine synthesis by estradiol is lost. These cytokines, including interleukin-1B (IL-1B), interleukin-6 (IL-6) and tumor necrosis factor-a (TNFa), contribute to bone resorption and development of atherogenic lesions. Although the fundamental influence of estradiol on post-menopausal health is unquestioned, the potential influence of increased gonadotropin concentrations, particularly follicle-stimulating hormone (FSH), has received less attention. This project will investigate potential mechanisms by which FSH may affect skeletal and vascular health, namely by stimulating IL-1B, IL-6 and TNFa secretion and inhibiting the shedding of receptors for these cytokines. These mechanisms will be studied using leukocytes isolated from the peripheral blood of pre-and peri-menopausal women. In addition, the biological significance of these mechanisms will be assessed by comparing plasma FSH, cytokine and cytokine receptor concentrations with circulating markers of bone turnover (N-telopeptide and osteocalcin), bone densities measured by dual energy X-ray absorptionmetry, and indices of vascular health (carotid intimal-medial thickness and pulse wave velocity measured by ultrasound). A better understanding of FSH-mediated mechanisms in peri-and postmenopausal health may lead to new therapies directed at modulation of FSH that can alleviate menopausal health problems without the attendant risks associated with steroid hormone replacement therapy.

描述（由申请人提供）：绝经过渡涉及循环卵巢类固醇的急剧减少和循环下丘脑促性腺激素的急剧增加。雌激素流失对与衰老和更年期相关的健康问题（例如骨质疏松症和心血管疾病）的生物学影响已得到广泛研究。第一个结果是雌二醇对炎症细胞因子合成的强效抑制作用消失。这些细胞因子，包括白细胞介素-1B (IL-1B)、白细胞介素-6 (IL-6) 和肿瘤坏死因子-a (TNFa)，有助于骨吸收和动脉粥样硬化病变的发展。尽管雌二醇对绝经后健康的根本影响是毋庸置疑的，但促性腺激素浓度增加，特别是促卵泡激素（FSH）的潜在影响却很少受到关注。该项目将研究 FSH 影响骨骼和血管健康的潜在机制，即通过刺激 IL-1B、IL-6 和 TNFa 分泌并抑制这些细胞因子受体的脱落。将使用从绝经前和围绝经期妇女的外周血中分离的白细胞来研究这些机制。此外，这些机制的生物学意义将通过比较血浆 FSH、细胞因子和细胞因子受体浓度与骨转换循环标志物（N-端肽和骨钙素）、双能 X 射线吸收法测量的骨密度以及血管健康指数（颈动脉内膜中层厚度和脉搏波速度）进行评估。 超声波）。更好地了解围绝经期和绝经后健康中 FSH 介导的机制可能会导致针对 FSH 调节的新疗法，从而缓解更年期健康问题，而不会产生与类固醇激素替代疗法相关的风险。

项目成果

Follicle-stimulating hormone promotes RANK expression on human monocytes.

• DOI: 10.1016/j.cyto.2010.11.011
• 发表时间: 2011-02
• 期刊: Cytokine
• 影响因子: 3.8
• 作者: Cannon JG;Kraj B;Sloan G
• 通讯作者: Sloan G

Soluble TNF and IL-6 receptors: indicators of vascular health in women without cardiovascular disease.

• DOI: 10.1177/1358863x13508336
• 发表时间: 2013-10
• 期刊: Vascular medicine (London, England)
• 作者: Cortez-Cooper M;Meaders E;Stallings J;Haddow S;Kraj B;Sloan G;McCully KK;Cannon JG
• 通讯作者: Cannon JG