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 r at gonads and mesonephroi was studied in vitro by using H-3 thymidin e autoradiography to evaluate the role of activin in the regulation of gonadal development. mRNA levels of inhibin-beta(A) and -beta(B), act ivin receptor II and IIB (ActRII and ActRIIB), and follistatin were st udied by Northern hybridization in the fetal rat gonads and mesonephro i. Activin stimulated thymidine incorporation in ovaries and female me sonephroi on days 14 and 15 postcoitum (pc) in a dose-dependent manner , as assessed by autoradiography. In contrast, activin inhibited thymi dine incorporation in testes and male mesonephroi on day 14 pc in a do se-dependent way. On day 18 pc, the stimulatory effect of activin in o vary 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 teste s and mesonephroi in the male and in mesonephroi in the female of 15 a nd 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 te stes and ovaries from 15 day pc onward. ActRIIB mRNA was most abundant in the testes, ovaries, and mesonephroi of 15 day pc embryos. The exp ression of ActRIIB message diminished during aging. ActRII mRNA was ub iquitously expressed during development. Follistatin mRNA was seen in the ovaries from 15 day pc onward and in the oviducts at 11 days postn atally. The present novel findings of activin subunit and receptor mRN A expression and activin action on gonadal and mesonephric cell prolif eration suggest an important, sexually dimorphic role for this substan ce in fetal gonadal differentation.