Mammalian spermatogenesis is a hormone-dependent process regulated mainly by follicle-stimulating hormone (FSH) and testosterone (T). The effects of these hormones on germ cell (Gc) differentiation are believed to be indirect, mediated through the somatic Sertoli cells (Sc). Although T and/or FSH were shown to affect various Sc functions, including the secretion of many proteins (i.e., androgen binding protein, inhibin, transferrin, plasminogen activator), the mechanism by which the Sc mediates the hormonal effects on the Gc is not known. The overall objective of this proposal is to clarify the Sc-Gc interaction by further exploring a hypothesis that certain products which may be required by the Gc, are produced by the Sc and are transferred to the Gc during certain stages of their differentiation.
The specific aims are: 1) to investigate the uptake of some prelabeled Sc products (peptides, proteins, glycoproteins and RNA) by the Gc at specific stages of differentiation, by using radioautography and isotope counting methods. During the initial grant period, we obtained evidence for high affinity, specific binding of androgen binding protein to the pachytene spermatocytes, and binding of transferrin to both pachytene spermatocytes and round spermatids, suggesting that some Sc products may be transferred to the Gc by a receptor-mediated mechanism; 2) to explore the effects of FSH and T on the secretion and transfer of the Sc products; 3) to identify the chemical nature of the transferred Sc products, not yet characterized, by using various immunologic (RIA, immunoprecipitation, immunofluorescence) and biochemical (two-dimensional gel electrophoresis, Western blots, HPLC, etc.) methods; 4) to examine if there is a correlation between the transfer of specific Sc products and Gc differentiation. These studies should provide additional information on the mechanism by which hormones regulate spermatogenesis and on the role of Sertoli cells in this process.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD017802-05
Application #
3314833
Study Section
Reproductive Biology Study Section (REB)
Project Start
1983-09-30
Project End
1989-03-31
Budget Start
1987-09-01
Budget End
1989-03-31
Support Year
5
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Texas Health Science Center Houston
Department
Type
Schools of Medicine
DUNS #
City
Houston
State
TX
Country
United States
Zip Code
77225
Kaiser, U B; Jakubowiak, A; Steinberger, A et al. (1997) Differential effects of gonadotropin-releasing hormone (GnRH) pulse frequency on gonadotropin subunit and GnRH receptor messenger ribonucleic acid levels in vitro. Endocrinology 138:1224-31
Kaiser, U B; Jakubowiak, A; Steinberger, A et al. (1993) Regulation of rat pituitary gonadotropin-releasing hormone receptor mRNA levels in vivo and in vitro. Endocrinology 133:931-4
Steinberger, A; Klinefelter, G (1993) Sensitivity of Sertoli and Leydig cells to xenobiotics in in vitro models. Reprod Toxicol 7 Suppl 1:23-37
Jakubowiak, A; Janecki, A; Tong, D et al. (1991) Effects of recombinant human inhibin and testosterone on gonadotropin secretion and subunit mRNA in superfused male rat pituitary cell cultures stimulated with pulsatile gonadotropin-releasing hormone. Mol Cell Endocrinol 82:265-73
Janecki, A; Jakubowiak, A; Steinberger, A (1991) Effects of cyclic AMP and phorbol ester on transepithelial electrical resistance of Sertoli cell monolayers in two-compartment culture. Mol Cell Endocrinol 82:61-9
Janecki, A; Jakubowiak, A; Steinberger, A (1991) Regulation of transepithelial electrical resistance in two-compartment Sertoli cell cultures: in vitro model of the blood-testis barrier. Endocrinology 129:1489-96
Janecki, A; Jakubowiak, A; Steinberger, A (1990) Vectorial secretion of inhibin by immature rat Sertoli cells in vitro: reexamination of previous results. Endocrinology 127:1896-903
Jakubowiak, A; Janecki, A; Steinberger, A (1990) Kinetics of inhibin secretion in static and superfused Sertoli cell cultures in response to follicle-stimulating hormone. Biol Reprod 43:939-45
Jakubowiak, A; Janecki, A; Steinberger, A (1990) Action kinetics of inhibin in superfused pituitary cells depend on gonadotropin-releasing hormone treatment. Endocrinology 127:211-7
Castellon, E; Janecki, A; Steinberger, A (1989) Age-dependent Sertoli cell responsiveness to germ cells in vitro. Int J Androl 12:439-50

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