Androgen-binding (ABP) is produced by the Sertoli cells of the testis. Although the function(s) of ABP is unknown, the possibility that it may be involved in spermatogenesis, in sperm maturation, or in the regulation of epididymal function has prompted extensive research on the molecule. ABP may also serve as a marker for Sertoli cell function. Since these cells are intimately associated with the developing germ cells, information regarding their function could be of value in diagnosing cases of infertility and for developing agents that interfere with Sertoli cell or ABP function thus leading to methods of male contraception. We propose to perform the following studies in immature (25 day-old) and adult male rats: 1) To use photoaffinity labeled ABP and immunochemical methods to study the distribution, fate, and metabolism of ABP. 2) To determine whether membrane receptors for ABP can be detected in potential target tissues under in vitro conditions. 3) To examine the physicochemical nature of ABP in plasma and compare it with ABP in the testis-epididymis compartment. and 4) To develop polyclonal antibodies against ABP to identify and quantitate it in tissues and fluids, and to obtain information on its possible function. A comparison of the distribution of bioreactive (measured using photolabeled ABP) and immunoreactive ABP will provide information on its sites of utilization or degradation. Autoradiography at the EM level could elucidate the cell biology of ABP uptake. We will study the specificity and kinetics of the interaction of [125I] ABP with homogenates and/or membrane fractions from potential target tissues to determine if classical receptors exist for ABP. The comparison of ABP from plasma and the testis-epididymis will be done using denaturing and non-denaturing PAGE, isoelectricfocusing, ion exchange chromotography, and immunological techniques. These studies will reveal the physicochemical nature and microheterogeneity of bioreactive ABP's. If neutralization of endogenous ABP leads to discrete alterations in reproductive function (e.g., changes in spermatogenesis, in epididymal morphology, or in sperm maturation), information on the function of ABP will be obtained. The proposed studies will provide unique information concerning similarities and differences that might exist between bioreactive and immunoreactive forms of the molecule and on the role of ABP in male reproductive function.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD013813-06
Application #
3312343
Study Section
Reproductive Biology Study Section (REB)
Project Start
1981-07-01
Project End
1988-06-30
Budget Start
1986-12-01
Budget End
1988-06-30
Support Year
6
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37203
Danzo, B J (1995) The effects of a gonadotropin-releasing hormone antagonist on androgen-binding protein distribution and other parameters in the adult male rat. Endocrinology 136:4004-11
Diaz Cruz, P J; Danzo, B J; Smith, H E (1995) Active-site-directed photoaffinity radioiodination of androgen-binding proteins. Steroids 60:256-60
Danzo, B J; Joseph, D R (1994) Structure-function relationships of rat androgen--binding protein/human sex-hormone binding globulin: the effect of mutagenesis on steroid-binding parameters. Endocrinology 135:157-67
Cruz, P J; Mason, N S; Danzo, B J et al. (1992) Preparation of 17 alpha-iodoethynylandrosta- and 17 alpha-(2-iodoethenyl)androsta-4,6-dien-17 beta-ol-3-ones as active site-directed photoaffinity ligands for androgen-binding proteins. Steroids 57:569-76
Joseph, D R; Lawrence, W; Danzo, B J (1992) The role of asparagine-linked oligosaccharides in the subunit structure, steroid binding, and secretion of androgen-binding protein. Mol Endocrinol 6:1127-34
Danzo, B J; Parrott, J A; Skinner, M K (1991) Analysis of the steroid binding domain of rat androgen-binding protein. Endocrinology 129:690-6
Danzo, B J; Black, J H; Bell, B W (1991) Analysis of the oligosaccharides on androgen-binding proteins: implications concerning their role in structure/function relationships. J Steroid Biochem Mol Biol 40:821-31
Turner, T T; Roddy, M S (1990) Intraluminal androgen binding protein alters 3H-androgen uptake by rat epididymal tubules in vitro. Biol Reprod 43:414-9
Danzo, B J; Black, J H (1990) Analysis of the oligosaccharides on rat androgen-binding protein using serial lectin chromatography. Biol Reprod 43:219-28
Danzo, B J; Pavlou, S N; Anthony, H L (1990) Hormonal regulation of androgen-binding protein in the rat. Endocrinology 127:2829-38

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