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Highlights

On page 1151, Tan et al. report their finding that androgen regulates stage-dependent expression of cyclin D2 in Sertoli cells. Although it is virtually certain that androgens regulate spermatogenesis in mammals, the pathways involved are not known. Because germ cells lack an androgen receptor, androgen action on germ cells has long been thought to be mediated by Sertoli cells. This was demonstrated last year when two groups independently produced Sertoli cell-selective knockouts of the androgen receptor, with a phenotype of spermatogenic arrest in meiosis. Now Tan et al. use experimental down-regulation of androgen action on Sertoli cells to visualize stage-specific expression of cyclin D2 protein. Cyclin D2 expression was highest at stages when androgen receptor expression is normally low, and non-detectable at stages when androgen receptor expression is normally high. Cyclin D2 may affect spermatogenesis through a downstream effector, the retinoblastoma 1 protein, and expression of this parallels androgen receptor expression. These results are significant because they help clarify how androgens regulate spermatogenesis via Sertoli cells and implicate a non-cell-cycle role for cyclin D2 in mature Sertoli cells.

Male Reproductive Timing in Rhesus Macaques Is Influenced by the 5HTTLPR Promoter Polymorphism of the Serotonin Transporter Gene. Michael Krawczak, Andrea Trefilov, John Berard, Fred Bercovitch, Matthew Kessler, Ulrike Sauermann, Peter Croucher, Peter Nurnberg, Anja Widdig, and Jorg Schmidtke. Biol Reprod 2005; 72:1109–1113. Published online 5 January 2005; 10.1095/biolreprod.104.038059

On page 1109, Krawczak et al. report an investigation of a genetic factor influencing male timing in offspring production. Reproductive timing during the life span of an individual is highly variable at the level of the individual and the population. It may be influenced by proximal factors, such as nutrient availability, social hierarchy, and predation. Krawczak et al. used a well-characterized free-ranging population of rhesus macaques to ask if specific gene allele combinations could affect reproductive life history. The serotonin transporter has two alleles, known as "long" and "short." The short form, which reduces translational efficiency, has been associated with stress responses, anxiety, and depression in humans. Analogous alleles exist in rhesus macaques. In this study, the allele combinations (homozygous versus heterozygous) were shown to influence when males reproduce, with notable differences in timing of offspring production between males with different serotonin transporter genotypes. This phenomenon appears to be due, at least in part, to the effects of these alleles on the timing of male migration from the natal group, and demonstrates that a specific genetic allele can influence reproductive life span in a primate.

The Helix-Loop-Helix Inhibitor of Differentiation Proteins Induce Post-Mitotic Terminally Differentiated Sertoli Cells to Re-Enter the Cell Cycle and Proliferate. Jaideep Chaudhary, Ingrid Sadler-Riggleman, Jacquelyn M. Ague, and Michael K. Skinner. Biol Reprod 2005; 72: 1205–1217. Published online 12 January 2005; 10.1095/biolreprod.104.035717

Differentiated Sertoli cells, which function to support male germ cell development, do not replicate after onset of puberty. What causes Sertoli cells to enter and maintain the terminally differentiated state is a major question of male reproductive biology. In the study by Chaudhary et al, on page 1205, differentiated rat Sertoli cells were transfected with constructs to drive the overexpression of human inhibitor of DNA-binding (ID1 and ID2) genes, which encode proteins thought to suppress differentiation and promote cell proliferation. The transfected Sertoli cells re- entered the cell cycle and resumed proliferation, with numerous cell replications. It is exciting to speculate that similar control mechanisms sustain other terminally differentiated cell types and that the IDB proteins could be harnessed to entice them to proliferate for therapeutic purposes.

John Eppig, Mary Ann Handel, and Sue Moenter

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Eppig, J. Articles by Moenter, S. Search for Related Content PubMed Articles by Eppig, J. Articles by Moenter, S. Agricola Articles by Eppig, J. Articles by Moenter, S.