Effects of Growth Hormone, Activin, and Follistatin on the Development of Preantral Follicle from Immature Female Mice

The aim of this study was to investigate whether GH and insulin-like growth factor I (IGF-I) are involved in preantral folliculogenesis and, if so, to clarify the relationship between GH/IGF-I and activin/follistatin (FS) systems in immature female mice. Ovaries were obtained from 11-day-old mice, and preantral follicles, 100–105 μm in diameter, were mechanically isolated and selected for culture. Ten preantral follicles per well were cultured with different quantities and combinations of additives as follows: no additives (control), recombinant human FSH (rhFSH), IGF-I, recombinant human GH (rhGH), activin A, and recombinant human FS (rhFS). Mean diameters of the follicles were measured daily, and estradiol and immunoreactive inhibin levels in the cultured medium were assayed by RIA on day 4. rhGH showed stimulatory effects on the follicular diameter and the secretion of estradiol and immunoreactive inhibin. These effects were augmented by the presence of IGF-I and activin A. IGF-I alone did not show any stimulatory effect. The addition of rhFSH to activin A or to rhGH and activin A promoted preantral follicular growth and hormone production. On the other hand, GH- or activin-stimulated follicular growth was suppressed by rhFS in a dose-dependent manner. These results indicate that activin A and rhGH may play an important role in controlling earlier phases of follicular development during the infantile period, which is considered to be gonadotropin independent.