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Activin Modulates Differential Effects of Estradiol on Synthesis and Secretion: DISCUSSION(1)


Current concepts of regulation of gonadotrope function include the autocrine-paracrine regulation of FSH synthesis and secretion by activin and follistatin. Some reports have documented small but significant increases in mRNAs for activin pB and inhibin a after gonadectomy in rats. Alternatively, effects of activin action on expression of FSHp may be mediated via changes in production of follistatin. The amount of pituitary mRNA for follistatin increases during proestrus in the rat. This seems incongruous with the idea that follistatin sequesters activin and thereby reduces synthesis and secretion of FSH. Furthermore, pituitary content of follistatin and free activin are inversely related during the estrous cycle, and free activin peaks during the cycle and appears to be responsible for a large portion of the secondary surge of FSH in the rat.

We have demonstrated that activin has a specific effect on FSH secretion in sheep. In fact, treatment of cultured anterior pituitary cells with a monoclonal antibody to activin pB decreased secretion of FSH, but did not alter release of LH. The antibody should neutralize activin B, the primary form of activin present in the anterior pituitary gland, and activin AB. This indicates that activin acts through a paracrine or autocrine mechanism to stimulate secretion of FSH even in absence of hypothalamic input. Furthermore, our data show that the genes for pB and follistatin are expressed in ovine pituitary cells during anestrus.