EXPRESSION OF ACTIVIN RECEPTOR-II AND RECEPTOR-IIB MESSENGER-RNA ISOFORMS IN MOUSE REPRODUCTIVE-ORGANS AND OOCYTES

Activins, the dimeric polypeptides of inhibin beta-subunits, exhibit p aracrine effects on cell proliferation, differentiation, and various o ther cell functions. The complex biological response to activin appear s to involve multiple receptors. In the present study, we examined the isoform mRNA expression of both activin receptor type II (ActR-II) an d type IIB (ActR-IIB) genes in mouse reproductive organs, cumulus-oocy te complexes (COCs), and ovulated oocytes. Northern blot analyses of f emale and male reproductive organs with single-stranded ActR-II cDNA p robes revealed that mouse ovaries expressed high levels of the 6.0 kil obase (kb) mRNA, whereas the 3.0 kb transcript was the major mRNA spec ies found in the testis. Reverse transcriptase-polymerase chain reacti on (RT-PCR) showed that both COCs and oocytes contained ActR-II mRNA. To examine the expression of ActR-IIB gene, primer selection was made outside the two alternative splicing sites in order to amplify the cDN As of all four distinct receptor isoforms. The results of RT-PCR demon strated that isoforms IIB2 and IIB4 were the major mRNA species expres sed in both female and male gonads and extragonadal reproductive tissu es. The ovary expressed all four mRNA isoforms, whereas the testes exp ressed only three isoforms. Furthermore, COCs and oocytes contained on ly the ActR-IIB2 isoform. The differential expression of both activin receptor mRNA isoforms in the reproductive organs suggests that distin ct alternative splicing mechanisms are involved in activin receptor ge ne expression in male and female gonads, and that each of the activin receptors may have its own biological function in reproduction. The ex pression of activin receptor genes in COCs and oocytes indicates that activin, produced by the granulosa cells of maturing follicles, may ac t locally to regulate follicular development and oocyte maturation. (C ) 1994 Wiley-Liss, Inc.