ONTOGENY OF FSH RECEPTOR MESSENGER-RIBONUCLEIC-ACID TRANSCRIPTS IN RELATION TO FSH-SECRETION AND TESTICULAR FUNCTION IN SHEEP

The role of alternative splicing of the FSH receptor gene in the gener ation of FSH receptor proteins and testicular function remains an enig ma. To address this issue, this investigation was conducted to determi ne variations in the expression of alternate FSH receptor mRNA transcr ipts in relation to changes in FSH release, hormone binding activity a nd testicular function during pubertal development of ram lambs from t wo genotypes of sheep (Romanov and a cross between Booroola x DLS) wit h different sexual precocity. Serum 17 beta-estradiol and testosterone concentrations were used as indices of Sertoli cell and testicular fu nction. The results indicated that increases in Sertoli cell and testi cular function normally seen during pubertal development are accompani ed by age-dependent reductions in concentration of functional FSH rece ptors, as determined by binding of iodinated FSH to testicular membran e preparations. During the course of these changes, FSH release was ei ther maintained at a steady level in Romanov lambs or it was gradually reduced in the Booroola x DLS cross, thus indicating that the testis had become more responsive to hormonal signal. This acquisition of hei ghtened sensitivity was also associated with contrasting changes in th e level of expression of FSH receptor mRNA transcripts. For both genot ypes of sheep, 5 distinct species of mRNA transcripts of approximately 1.1, 1.5, 2.0, 2.5 and 6.5 kb were highly expressed from 11 to 22 wee ks of age. Amongst these transcripts, the 1.1 kb molecular species was the most abundant. Specific probing for a previously cloned transcrip t called 151A1 representing the first 4 exons of the FSH receptor gene revealed a paradoxical increase in the level of expression from 11 we eks up to a maximum at 18-22 weeks of age for both genotypes. Collecti vely, the results indicated that contrasting changes in the production of specific alternatively spliced mRNA transcripts may mediate change s in FSH receptor expression which apparently accounts for the augment ation in sensitivity and function of the testis during pubertal develo pment. Furthermore, the data provide the first important indication th at the novel truncated transcript (151A1), which predictably encodes a soluble protein of either intra- or extracellular fate, could be phys iologically relevant.