Effects of FSH on testicular mRNA transcript levels in the hypogonadal mouse

Follicle stimulating hormone (FSH) acts through the Sertoli cell to ensure normal testicular development and function. To identify transcriptional mechanisms through which FSH acts in the testis we have treated gonadotrophin-deficient hypogonadal (hpg) mice with recombinant FSH and measured changes in testicular transcript levels using microarrays and real-time PCR 12, 24 and 72h after the start of treatment. Approximately 400 transcripts were significantly altered at each time point by FSH treatment. At 12h there was a clear increase in the levels of a number of transcripts known to be expressed in the Sertoli cells (eg Fabp5, Lgals1, Tesc, Scara5, Aqp5). Additionally, level of Leydig cell transcipts were also markedly increased (eg Ren1, Cyp17a1, Akr1b7, Star, Nr4a1). This was associated with a small but significant rise in testosterone at 24 and 72h. At 24h, androgen-dependent Sertoli cell transcripts were upregulated (eg Rhox5, Drd4, Spinlw1, Tubb3 and Tsx) and this trend continued up to 72h. Surprisingly, only 4 germ cell trancripts (Dkkl1, Hdc, Oct4 and 1700021K02Rik) were altered by FSH within the time-course of the experiment. Pathway analysis showed changes in cell cycle and cell proliferation pathways at all times and a general decline in transcripts related to formation and regulation of tight junctions. Results show FSH acts directly and indirectly to induce rapid changes in Sertoli cell and Leydig cell transcript levels in the hpg mouse but that effects on germ cell development must occur over a longer time span