| Activins are polypeptide hormones which belong to the transforming growth factor-ß (TGF-ß) superfamily. The TGF-ß superfamily is a large group of extra-cellular growth factors which control many aspects of development, reproductive function and tumor formation (1). Other members incude TGF-ßs, bone morphogenetic proteins, growth differentiation factors, AMH/MIS (Anti-Mullerian Hormone/Mullerian Inhibiting Substance) and Inhibins.
Activins and Inhibins are structurally related gonadal dimeric glycoproteins defined by their ability to modulate the synthesis and release of follicle-stimulating hormone (FSH) from the anterior pituitary gland. Activins are homo- or heterodimers consisting of ßA or ßB subunits producing Activin A, B, and AB, and have been shown to stimulate FSH release. Inhibins are heterodimers consisting of a common a-subunit linked to either a ßA subunit (Inhibin A) or ßB subunit (Inhibin B) by disulfide bridges, and in contrast to the Activins, inhibit FSH release. Messenger RNA studies demonstrate that both Inhibin and Activin are most abundant in the ovary and testis, but can be found in a variety of other tissues (2). In addition to their endocrine role, these proteins have been shown to affect the growth and differentiation of a number of cell types, including cultured rat anterior pituitary cells, gonadal and neuronal cell lines, and hematopoietic progenitor and erythroleukemia cells (2).
Two binding proteins have been described for the Activins and Inhibins: Follistatin and a-2 macroglobulin. Activins are bound with high affinity to follistatin with a possible regulatory role, while both inhibins and activins are found to bind reversibly with a2-macroglobulin (3).
Despite numerous studies investigating the circulating levels of the various activin molecules in numerous disease states, no clear physiological roles have been established other than the stimulatory action on pituitary FSH secretion. However, a number of recent studies have indicated that the measurement of Activin may be useful as a predictor of pre-eclampsia (4,5), preterm labor (6) and various oncological conditions (7).
- Chang H et al. Endocrine Rev 23: 787-823, 2002.
- Meunier H et al. Proc Natl Acad Sci USA 85: 247-251, 1988.
- Krummen LA et al. Endocrinology 132: 431-443, 1993.
- Muttukrishna S et al. Lancet 349:1285-1288, 1997.
- Muttukrishna S et al. Hum Reprod 15(7):1640-1645, 2000.
- Lockwood GM et al. Biol Reprod 57(6):1490-1494, 1997.
- Lambert-Messerlian GM et al. Gynecol Oncol 74(1):93-97, 1999.
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