Activin A increases the number of follicle-stimulating hormone cells in anterior pituitary cultures

The mode of action of activin A on the anterior pituitary gland (AP) was investigated using primary cultured cells. The AP cells were cultured with activin A (1 ng/ml) at various cell densities for 24-96 h, and further incubated for 3 h with activin A-free medium. When the cells were pretreated with activin A for 48 h, follicle-stimulating hormone (FSH) secretion during the following 3-h incubation was increased only at a density of 1 × 10⁵ cells/200 mm², but not at 2 × 10⁵ or 4 × 10⁵ cells/200 mm². A longer pretreatment (96 h) was required in order to induce this response at a density of 2 × 10⁵ cells/200 mm². Luteinizing hormone (LH) secretion was not affected by activin A. Thus, the FSH secretory activity of the primary culture of AP was stimulated by activin A in a cell density-dependent manner. Furthermore, it was found that treatment with activin A (10 ng/ml) for 72 h increased the number of immunoreactive FSH cells by 25-41%, and that these newly induced FSH cells were low responders to gonadotropin-releasing hormone stimulation. The proportions of immunoreactive LH, thyroid-stimulating hormone, prolactin or growth hormone cells were not affected. From these results, we conclude that activin A increases FSH secretion by changing the cell population of pituitary gonadotropes.