SEX DIFFERENCE IN THE ACTION OF ACTIVIN-A ON CELL-PROLIFERATION OF DIFFERENTIATING RAT GONAD

The effect of recombinant bovine activin-h on DNA synthesis in fetal rat gonads and mesonephroi was studied in vitro by using [H-3] thymidine autoradiography to evaluate the role of activin in the regulation of gonadal development. mRNA levels of inhibin-beta(A) and -beta(B), activin receptor II and IIB (ActRII and ActRIIB), and follistatin were studied by Northern hybridization in the fetal rat gonads and mesonephroi. Activin stimulated thymidine incorporation in ovaries and female mesonephroi on days 14 and 15 postcoitum (pc) in a dose-dependent manner, as assessed by autoradiography. In contrast, activin inhibited thymidine incorporation in testes and male mesonephroi on day 14 pc in a dose-dependent way. On day 18 pc, the stimulatory effect of activin in ovary was nearly lost, whereas that in mesonephros was still pronounced. Activin had no effect on thymidine incorporation in testes and male mesonephroi on day 15 or 18 pc. Inhibin-beta(A) mRNA was seen in testes and mesonephroi in the male and in mesonephroi in the female of 15 and 18 day pc embryos. Inhibin-beta(A) mRNA expression was also seen in the testes and epididymes of newborn male rats and in the ovaries of 11-day-old postnatal rats. Inhibin-beta(B) mRNA was present in both testes and ovaries from 15 day pc onward. ActRIIB mRNA was most abundant in the testes, ovaries, and mesonephroi of 15 day pc embryos. The expression of ActRIIB message diminished during aging. ActRII mRNA was ubiquitously expressed during development. Follistatin mRNA was seen in the ovaries from 15 day pc onward and in the oviducts at 11 days postnatally. The present novel findings of activin subunit and receptor mRNA expression and activin action on gonadal and mesonephric cell proliferation suggest an important, sexually dimorphic role for this substance in fetal gonadal differentation.