EXPRESSION OF MESSENGER RIBONUCLEIC-ACIDS ENCODING THE INHIBIN/ACTIVIN SYSTEM DURING MID-GESTATION AND LATE-GESTATION RAT EMBRYOGENESIS

We recently demonstrated that inhibin/activin alpha-, beta A-, and beta B-subunit messenger RNAs (mRNAs) are localized in a variety of embryonic rat tissues from 12-20 days post coitum (pc) and reported localizations consistent with possible growth effects of activin during rat embryogenesis. In the present study, we examined the tissue-specific distribution of mRNAs encoding all known players of the inhibin/ activin system. In situ hybridization with radiolabeled RNA probes specific for mouse activin receptors (ActRII and ActRIIB), rat follistatin, and rat inhibin/activin subunits was used to examine the spatiotemporal expression of these molecules in adjacent sections of postimplantation rat embryos (8-20 days pc) as well as in midgestation placenta and uterine tissues (8-12 days pc). With the exception of the dorsal root ganglion and salivary gland, alpha- and beta B-subunit mRNAs were found exclusively in reproductive tissues (brain, pituitary, and/or gonads). beta A-Subunit mRNA signal was observed in the brain and gonads as well as in a variety of other tissues during embryogenesis. ActRII mRNA was found exclusively in neuronal tissue from 14 days pc until birth. ActRIIB mRNA was also found in brain, spinal cord, and ganglion, but usually appeared earlier in development than the ActRII message. ActRIIB message was also expressed in a number of other tissues, in some cases along with beta A-subunit mRNA. In these tissues, ActRIIB expression was confined to epithelial and endothelial cell types. Follistatin message was observed in all tissues (except the heart and vessels) localizing beta A-subunit and/or ActRIIB but not in the same cell type. Outside the embryo, beta A-subunit mRNA was localized in the decidua capsularis during midgestation, whereas ActRIIB message was found in placenta as early as 9 days pc. Expression of follistatin message was apparent in decidua from 8-11 days pc, then disappeared from this tissue and was abundant in myometrium at 12 days pc. These data suggest that: 1) inhibin and activin regulate aspects of the fetal reproductive system, whereas activin A may regulate the growth and differentiation of many embryonic tissues; 2) ActRII and ActRIIB serve different roles during development of the rat embryo; and 3) follistatin is in a position to modulate the effects of activin during postimplantation rat embryogenesis.