Investigation into the role of HOX factors in gonad and adrenal steroidogenesis

HOX因子在性腺和肾上腺类固醇生成中的作用研究

• 批准号: G0901645/1
• 负责人: Amanda Swain
• 金额: $ 48.78万
• 依托单位: Institute of Cancer Research
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0901645%2F1
• 关键词: Investigation; into; role; HOX; factors

The gonad and adrenal cortex are derived from a common progenitor cell population and actively produce steroids during embryonic development. The regulation of steroid production in these organs and the factors that account for steroid specificity are not well understood. In this proposal we aim to investigate the role of members of the HOX family of transcription factors in the regulation of steroid production in the gonad and adrenal. HOX factors have been shown to regulate patterning in the embryo and our preliminary experiments indicate that they contribute to organ specific steroid production. We have identified HOXB9 as being expressed in the adrenal cortex but not the gonad and, conversely, we have identified HOXD9 as being gonad, but not adrenal, specific. Misexpression of HOXB9 in the gonad of transgenic mice gave rise to an increase in the presence of genes encoding enzymes involved in adrenal specific steroid production. We plan to use a combination of approaches including analysis of transgenic mice and tissue and organ culture experiments to determine the role of these HOX factors in steroidogenesis. As an extension of these studies we will investigate the ability of HOXB9 to cooperate with the nuclear hormone receptor SF-1 to induce the differentiation of adrenal steroid production in embryonic stem (ES) cells. SF-1 is a nuclear hormone receptor that has been shown to be required for the differentiation of steroid producing cells of the gonad and adrenal and can induce some aspects of steroid production in ES cells. Our studies will further these observations and may provide a framework for the production of steroid producing cells that may contribute to the development of novel therapies for patients with adrenal and gonadal failure.

性腺和肾上腺皮质来自常见的祖细胞群，并在胚胎发育过程中积极产生类固醇。这些器官中类固醇产生的调节以及涉及类固醇特异性的因素的调节尚不清楚。在此提案中，我们旨在调查Hox家族转录因子家族成员在性腺和肾上腺中类固醇产生的调节中的作用。 HOX因子已被证明可以调节胚胎中的模式，我们的初步实验表明它们有助于器官特定的类固醇产生。我们已经确定HOXB9在肾上腺皮质中表达，而不是性腺，相反，我们已经确定Hoxd9是性腺，但不是肾上腺，特定于肾上腺。在转基因小鼠性腺中，Hoxb9的mis​​expression在编码参与肾上腺特异性类固醇产生的酶的基因的存在下增加。我们计划使用多种方法组合，包括分析转基因小鼠，组织和器官培养实验，以确定这些HOX因子在类固醇发生中的作用。作为这些研究的扩展，我们将研究HOXB9与核激素受体SF-1合作诱导胚胎茎（ES）细胞中肾上腺类固醇产生的分化的能力。 SF-1是一种核激素受体，已被证明是分化性腺和肾上腺类固醇细胞所必需的，并且可以诱导ES细胞中类固醇产生的某些方面。我们的研究将进一步进一步观察，并可能为产生类固醇细胞的产生提供一个框架，这可能有助于为肾上腺和性腺衰竭患者开发新的疗法。