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.
