SEX STEROID-BINDING PROTEIN AND ANDROGEN ACTION

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Sex steroid-binding protein (SBP) is a high affinity binder of androgens in both males and females. Present in the circulation during fetal development in humans, SBP activity increases markedly during the postnatal period. Interestingly, in males there is a coincident postnatal surge in testosterone (T) with a large percentage of circulating T being bound by SBP. Although it has long been recognized that T not bound to SBP can enter tissues by passive diffusion, recent studies suggest SBP-bound T may be acting as a separate endocrine signal at the target cell level. Our long-term research objectives are to 1) identify the role of SBP in androgen action and 2) identify the factors responsible for the physiological regulation of the synthesis/secretion of this protein. The aims of this specific project period are to define the effects of SBP on male sexual differentiation and to identify factors which control SBP gene expression during the postnatal period. These investigations are being conducted in the Djungarian hamster and the little brown bat, two species which, like humans, exhibit marked increases in both SBP has been synthesized and it specifically hybridizes with a 2 kb RNA present in postnatal Djungarian hamster liver. Using this probe, as well as antisera which will be generated to purified Djungarian hamster SBP (DhSBP), postnatal changes in SBP gene expression will be defined and cDNA libraries will be screened to obtain clones for DhSBP. These clones will be sequenced and used to produce ribonucleotide probes for analysis of the control of tissue/cell-specific expression of SBP during postnatal development. Experiments will also be conducted to characterize sex difference in tissue specific binding and uptake of labeled SBP and to determine the effects of T on these processes. The effects of SBP on the uptake and metabolism of androgens during the postnatal period and the physiological role of SBP-androgen interactions in male sexual differentiation will be determined. These experiments will provide important information on both the physiological control of SBP and the role of SBP in androgen action.