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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD016535-09
Application #
3313736
Study Section
Reproductive Biology Study Section (REB)
Project Start
1983-04-01
Project End
1994-11-30
Budget Start
1991-12-01
Budget End
1992-11-30
Support Year
9
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Tufts University
Department
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02111
Cates, J M; Damassa, D A (1997) Characterization and developmental expression patterns of testicular androgen-binding protein in the Djungarian hamster (Phodopus sungorus). J Reprod Fertil 111:291-8
Damassa, D A; Gagin, G A; Gustafson, A W (1996) Purification and characterization of the sex hormone-binding globulin in serum from Djungarian hamsters. Comp Biochem Physiol B Biochem Mol Biol 113:593-9
Cates, J M; Damassa, D A; Gagin, G A et al. (1995) Hepatic expression of sex hormone-binding globulin associated with the postnatal surge of serum androgen-binding activity in the Djungarian hamster. J Steroid Biochem Mol Biol 55:147-58
Soto, A M; Lin, T M; Sakabe, K et al. (1995) Variants of the human prostate LNCaP cell line as tools to study discrete components of the androgen-mediated proliferative response. Oncol Res 7:545-58
Damassa, D A; Gustafson, A W; Kwiecinski, G G et al. (1995) Seasonal influences on the control of plasma sex hormone-binding globulin by T4 in male little brown bats. Am J Physiol 268:R1303-9
Kwiecinski, G G; Damassa, D A; Gustafson, A W (1991) Patterns of plasma sex hormone-binding globulin, thyroxine and thyroxine-binding globulin in relation to reproductive state and hibernation in female little brown bats. J Endocrinol 128:63-70
Damassa, D A; Lin, T M; Sonnenschein, C et al. (1991) Biological effects of sex hormone-binding globulin on androgen-induced proliferation and androgen metabolism in LNCaP prostate cells. Endocrinology 129:75-84
Gustafson, A W; Damassa, D A; Pratt, R D et al. (1989) Post-natal patterns of plasma androgen-binding activity in Djungarian (Phodopus sungorus) and golden (Mesocricetus auratus) hamsters. J Reprod Fertil 86:91-104
Damassa, D A; Gustafson, A W (1988) Effects of chronic infusions of sex steroid-binding protein on the testosterone-mediated inhibition of gonadotropin secretion and maintenance of sex accessory glands in male rats. Endocrinology 123:1885-92
Gustafson, A W (1987) Changes in Leydig cell activity during the annual testicular cycle of the bat Myotis lucifugus lucifugus: histology and lipid histochemistry. Am J Anat 178:312-25

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