BIOCHEMICAL ACTION OF STEROID HORMONES IN EUKARYOTES

本研究计划旨在开发一个独特的模型系统， 研究类固醇激素在靶细胞中的相互作用， 激素作用的生化机制。 雄激素是一种类固醇激素 在卵菌真菌Achlya中诱导雄性性别分化 两性人 这种水霉菌是最原始的真核生物 已知有性生殖由类固醇激素控制 系统 它应该为激素的研究提供一些优势 由于其相对简单的细胞组织和生殖作用， 系统 虽然这个有趣的系统的某些方面已经被研究过了 详细地说，直到最近，还不可能研究这些人的命运。 靶细胞中的激素或表征雄激素受体， 放射性标记的类固醇不可用。 我们成功地 合成[3 H]-7-脱氧-蒽二醇。 我们的初步研究表明， 具有生物活性并与细胞组分相互作用的化合物 以一种可饱和的方式。 这项建议的目的是 进一步表征已鉴定的结合组分， 可能存在的任何其他组件。 生物学意义 （受体样）成分将通过分析激素 结合特异性以及体内结合与 生物反应。 这些受体的特性将是 与在脊椎动物系统中发现的相比。 如果存在相似之处， 将表征受体系统的各种参数 使我们对这个系统的了解程度与对其他系统的了解程度相等。 已知的实验系统 如果Achlya系统与其他系统完全不同， 类固醇系统，这些差异将被建立， 表征了 这些调查应明确确立以下价值： Achlya作为一个实验模型，并将提供基础， 类固醇激素作用的生化机制研究。

This research proposal is designed to develop a unique model system to study the interactions of steroid hormones in target cells and the biochemical mechanism of hormone action. Antheridiol is a steroid hormone which induces male sexual differentiation in the oomycete fungus, Achlya ambisexualis. This water mold is the most primitive eukaryotic organism known in which sexual reproduction is controlled by a steroid hormone system. It should offer several advantages for investigations on hormone action due to its relatively simple cellular organization and reproductive system. Although some aspects of this interesting system have been studied in detail, until recently it has not been possible to study the fate of the hormone in target cells or to characterize an antheridiol receptor because the radiolabeled steroid was not available. We have succeeded in synthesizing [3H]-7-deoxy-antheridiol. Our initial studies show this compound to be biologically active and to interact with cellular components of Achlya in a saturable manner. The objective of this proposal is to further characterize the binding component(s) that have been identified and any additional components that may exist. The biologically significant (receptor-like) components will be established through analysis of hormone binding specificity and a positive correlation between in vivo binding and the biological response. The properties of these receptors will then be compared to those found in vertebrate systems. If similarities exist, various parameters of the receptor system will be characterized to rapidly make our degree of knowledge of this system equivalent to that of other known experimental systems. If the Achlya system is quite unlike other steroidal systems, these differences will be established and characterized. These investigations should clearly establish the value of Achlya as an experimental model and will provide the basis for future studies on the biochemical mechanism of steroid hormone action.