Alteration Of Cyclic Adenosine 3’,5’-Monophosphate Signaling In Rat Testicular Cells After Spinal Cord Injury

Abstract

Introduction: Earlier studies demonstrated that the effects of spinal cord injury (SCI) on spermatogenesis were associated with altered Sertoli cell responses to treatment with follicle-stimulating hormone (FSH) and/or testosterone (T). Because of the importance of the cyclic adenosine 3’,5’-monophosphate (cAMP) signal pathway in hormonal actions on Sertoli cells and spermatogenesis, the purpose of this study was to determine whether cAMP signaling in testicular cells is altered after SCI.Methods: Rats with SCI were treated with FSH, T, or FSH + T for 7 or 14 days. Northern blot cDNA hybridization was used to measure testicular levels of Sertoli and germ cell-specific transcripts encoded by genes that contain cAMP responsive element (CRE) and/or steroid hormone responsive element (HRE). Cellular distribution of CRE modulator (CREM) was determined by immunohistochemistry.Results: Treatment of sham control rats with FSH or T + FSH for 2 weeks resulted in decreases in mRNAs for CREM and CRE binding protein (CREB). Concomitantly, levels of mRNA for Sertoli cell inhibin a and germ cell-specific protamine 1 (Pm- 1), transition protein 2 (TP-2), and lactate dehydrogenase C (LDHC) were all reduced. In contrast, identical FSH and/or T treatments resulted in increases in levels of CREM and CREB mRNAs in the testes of SCI rats; these effects were associated with similar changes in mRNAs for inhibin α, Pm- 1, TP-2, and LDHC. The effects of SCion CREM expression were corroborated by similar changes in its distribution in testicular cells.Conclusion: SCI is associated with changes in FSH and/or T regulation of cAMP/CRE and HRE signaling in testicular cells. These effects may mediate the effects of SCion spermatogenesis.} Spinal Cord Med. 2003;26:69–78