Membrane transporters for sulfated steroid hormones in the testisand their role for spermatogenesis and fertility

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Circulating sulfated steroid hormones are delivered to target tissues via uptake carriers and then can be reactivated by the catalytic activity of the steroid sulfatase (StS) (“sulfatase pathway”). Although it is well known that in the human testis there is a high StS enzyme activity and DHEAS and PREGS can be metabolized to active testosterone by testis homogenates, little is known about the function, expression, and physiological significance of steroid sulfate carriers in the testis. The project is focused on the investigation of expression and regulation of membrane transporters for sulfated steroid hormones such as SOAT, OATP6A1, OATP1C1, and OSCP1 which show predominant expression in the testis as well as StS. We will investigate (1) the subcellular localization of steroid sulfate carriers and StS in the human testis comparing normal spermatogenesis and testicular biopsies with various pathological pictures to discriminate for pathological changes in the expression pattern, (2) generate stable HEK293 cell lines for each of the steroid sulfate carriers for comparative functional transport experiments, and will (3) analyze the androgen-dependent mRNA expression from SOAT, OATP6A1, and OATP1C1 genes, that all show highly conserved androgen-receptor response elements in their promoter sequences. The proposed work plan will provide new insights into the physiological relevance of the “sulfatase pathway” for the endocrine/intracrine regulation of testicular physiology and pathophysiology.