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* To whom correspondence should be addressed. E-mail: r.bayne{at}hrsu.mrc.ac.uk.
Gonadotropin withdrawal induces changes in gene expression in all three major cell types of the testis. Knowledge of the genes affected, in both the presence and absence of additional progestogen, will give insight into the regulation of human testicular function and aid development of novel contraceptive methods. We have undertaken a whole genome analysis of RNA expression in testicular biopsies from normal men and following 4 weeks gonadotropin suppression induced by Gonadotropin Releasing Hormone (GnRH) antagonist plus testosterone administration sufficient to cause marked suppression of spermatogenesis. Microarray analysis shows that inter-individual variability is markedly low and the response to treatment is focused on a small subset of genes particularly related to pathways in steroidogenesis and cholesterol biosynthesis or metabolism, the Leydig cell gene INSL3, and genes involved in early meiosis or Sertoli-germ cell junctions. These changes in expression were confirmed by quantitative Reverse Transcriptase- Polymerase Chain Reaction (RT-PCR). No major changes in gene expression were identified in men additionally treated with a progestogen although FLJ35767, an Expressed Sequence Tag (EST) which is expressed in the germ cell compartment, did show a small but significant additional effect of progestogen. Overall, the results of this investigation disclose a remarkably stringent regulation of testicular gene expression, revealing the genes most sensitive to gonadotropin withdrawal and may reflect the most labile pathways in the regulation of testicular function.
Key words: Contraception •
Reproductive Genetics •
Spermatogenesis •
Steroidogenesis •
Testis •
Microarray Analysis
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