The broad objective is to clarify the regulation of mammalian spermatogenesis, and the role played by Sertoli cells (Sc) in the endocrine and paracrine aspects of this prccess. The Sc are primary targets for follicle stimulating hormone (FSH) and testosterone (T) the main regulators of spermatogenesis -- and are believed to mediate the hormonal effects to germ cells through secretory products. Our hypothesis is that vectorial secretory patterns of Sc products and their regulation change during sexual maturation and that these changes may be important for the initiation of spermatogenesis. The proposed studies have four specific aims: 1) To characterize the vectorial patterns of Sc secretions including transferring ABP'inhibin and their regulation by FSH and T at several critical periods of sexual maturation; 2) To define the reciprocal relationship between FSH and T in Sc regulation by determining if increasing amounts of FSH can reduce the requirement for T and, conversely, if increasing amounts of T reduce the need for FSH during the progression of sexual maturation; 3) Using co- cultures, to clarify the paracrine influence of germ cells enriched populations of spermatogonia. spermatocytes and spermatids), peritubular myoid cells and Leydig cells on Sc secretions and their hormonal response. The relative importance of direct contact between Sc and germ cells on Sc secretion, as well as on germ cell survival and differentiation. will be assessed; 4) To investigate the vectorial secretion of FSA FSH- stimulating activity) which we recently found to be secreted by Sc in culture, and to characterize its physico-chemical nature. The Sc will be isolated from rats of different ages (18-60 d) and cultured in two-compartment culture systems (stationary and/or superfused developed in our laboratory. The products secreted into the apical and basal compartment will be assayed at several culture periods. The proposed studies should provide valuable information concerning Sc secretory patterns and their endocrine and paracrine regulation during progressive stages of sexual maturation. This information is important not only for the basic understanding of Sc functions and their role in spermatogenesis, but also for more rational approaches in clinical treatment of male infertiiity and in the development of male contraceptives.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
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Reproductive Biology Study Section (REB)
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University of Texas Health Science Center Houston
Schools of Medicine
United States
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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
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
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 (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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