Abstracts - Orals, Featured Poster Presentations, and Posters
SAT 381-386-Steroid Hormone Actions, Biosynthesis & Metabolism
Expo Halls ABC (Moscone Center)
Poster Board SAT-382
Nuclear receptors (NRs) and their coregulators are pivotal determinants of reproduction. SRA stem Loop Interacting RNA-binding Protein (SLIRP) is a potent repressor of NR activity including both androgen and oestrogen receptors. SLIRP is expressed in wild type (wt) male testis, where its distribution alters during spermatogenesis from weakly cytoplasmic in spermatogonia to head and neck associated in mature sperm suggesting a functional role within this tissue. In females, SLIRP is present within the reproductive tract and ovaries. To investigate the in vivo
effects of SLIRP, we have generated the SLIRP knock out (KO) mouse. This animal is viable, however both male and female KO mice have reduced fertility. Litters arising from KO males crossed with wt females are approximately 30% smaller than those from wt matings. Sperm analyses reveal that KO mice have 60% fewer progressively motile sperm than wt mice while electron microscopy demonstrates that the midpiece/principle piece junction is disrupted in SLIRP KO sperm. This is consistent with human micro-array data showing reduced SLIRP mRNA levels in sperm from teratozoospermic men compared to those of normal fertility. These data suggest that loss of SLIRP results in impaired male fertility, attributable in part, to compromised sperm motility.
We have also observed that litters born to SLIRP KO mothers are approximately 50% smaller than those from wt females. We have performed gene array studies comparing wt and SLIRP KO tissue and found that the immediate early transcription factor Egr-1 is markedly reduced in KO animals. Significantly, Egr-1 regulates the production of Luteinizing Hormone (LH) within the pituitary through its actions at the LHb promoter. Further, Egr1 KO female mice are infertile with an anoestrus phenotype1. We have now confirmed that SLIRP is expressed within the pituitary and its loss is associated with a significant reduction in Egr1 transcript levels in this organ. Current studies are expected to confirm a reduction in folliculogenesis in SLIRP KO mice as a result of compromised LH production. Taken together, these studies suggest that SLIRP is an important factor in the regulation of both male and female fertility.
1. Lee et al. (1996) Science, 273, 1219-1221.
Nothing to Disclose: SMC, LW, RS, VR, RF, SS, KD, DJM, JB, BGAS, LS, DMD, MKO, PJL
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Sources of Research Support:
National Health and Medical Research Council; Royal Perth Hospital Medical Reseach Foundation.