Alteration of follicle-stimulating hormone and testosterone regulation of messenger ribonucleic acid for Sertoli cell proteins in the rat during the acute phase of spinal cord injury

The detrimental effects of spinal cord injury (SCI) on spermatogenesis in t he rat can be attenuated by exogenous testosterone (T) but enhanced by exog enous follicle-stimulating hormone (FSH). These results suggest that T-depe ndent cellular events may be involved in testicular injury after SCI and th at such events may be associated with modification of FSH effects on Sertol i cell function. The current study compared the responses of Sertoli cells to exogenous T and FSH after SCI or sham surgery using steady-state levels of Sertoli cell protein mRNA transcripts as markers of responsiveness. Rats underwent sham surgery or SCI and then were treated for 7 or 14 days with T-filled silastic capsules (2 x 5 cm) and/or daily injections of 0.1 units of porcine FSH. Vehicle-treated control rats received 5-cm empty capsules a nd daily injections of saline vehicle. Two weeks after sham surgery, levels of mRNA for the androgen receptor (AR), FSH receptor (FSHR), androgen-bind ing protein (ABP), or sulfated glycoprotein (SGP)-2 in the testis were unaf fected by T or FSH alone. Testosterone alone, however, significantly decrea sed transferrin (Trf) mRNA levels in the testis (P < 0.01). The combination of T and FSH treatments resulted in significant decreases in levels of the above transcripts (P < 0.05; P < 0.01). Seven days after SCI, the testes o f vehicle-treated SCI rats had higher levels of AR and SGP-2 mRNA than did those of sham control rats (P < 0.01); such effects were transient and disa ppeared by Day 14 post-SCI. Testosterone treatment of SCI rats for 7 days r esulted in decreases in mRNA levels for AR and Trf in the testes (P < 0.01) but increased testicular levels of mRNAs for FSHR and SGP-2 in SCI rats. F ollicle-stimulating hormone treatment for 7 days prevented the increase in AR mRNA that was seen in the testis of untreated SCI rats and increased lev els of ABP and SGP-2 mRNAs in SCI rats (P < 0.01). Follicle-stimulating hor mone treatment of SCI rats did not affect FSHR mRNA levels by itself, but i t blocked the stimulatory effect of T on FSHR and SGP-2 mRNAs. Fourteen day s after SCI, testicular AR mRNA levels were not affected by T alone, but th ey increased in those rats that received FSH with or without concurrent T t reatments (P < 0.05). In contrast to their effects in sham control rats, T or FSH alone or in combination resulted in significant increases in testicu lar levels of ABP, SGP-P, and FSHR mRNAs (P < 0.05). At this time, Trf mRNA in the testis of SCI rats was also suppressed by T (P < 0.05), as it did i n sham control rats, but Trf mRNA was increased by the FSH (P < 0.01) that had inhibited this transcript in the testes of sham control rats. The effec ts of FSH on the Sertoli cell transcripts in SCI rats were either attenuate d or blocked when T was given concurrently. In addition, testicular and ser um T levels in those SCI rats that received FSH (alone or in combination wi th T) for 14 days were significantly increased, an effect that was not seen after sham surgery. These findings demonstrate that hormonal regulation of both Sertoli and Leydig cells was altered during the acute phase of SCI. S uch changes may modify the functions of both cell types, thereby affecting the endocrine and/or paracrine microenvironment within the seminiferous epi thelium. These effects could impair the functional capacity of Sertoli cell s and contribute to impairment of spermatogenesis after SCI.