Activin-related proteins in bovine mammary gland: Localization and differential expression during gestational development and differentiation

摘要

Bovine mammary gland morphogenesis and differentiation are regulated by actions of growth factors including members of the transforming growth factor β superfamily. Activins A and B, which are members of the transforming growth factor β superfamily, bind selectively to ActRIB and ActRIIA receptors and their biological effects are antagonized by inhibins and fol-listatins. In the present paper we evaluated gene and protein expression of the activin and inhibin subunits βA, βB, and α-inhibin and follistatin and ActRIB and ActRIIA receptors in the mammary gland of nonpreg-nant and pregnant heifers. Mammary glands were obtained from nonpregnant Nelore (Bos indicus) heifers (n = 9) and from primigravid Nelore heifers during early (n = 9), mid (n - 6), and late (n = 5) pregnancy. Specimens of mammary tissue were analyzed by realtime PCR and immunohistochemistry. The (3A and a-inhibin subunits and ActRIB and ActRIIA mRNA expression was higher in the early-pregnancy group compared with the nonpregnant group. In the mid-pregnancy group, the subunits βA, βB, and a-inhibin as much as follistatin mRNA expression was higher compared with the nonpregnant group, whereas ActRIB transcripts were absent in the late-pregnancy group. Immunostaining of these proteins, with the exception of ActRIB, was observed in the mammary tissue sections at all time points analyzed; these findings are in agreement with the observed pattern of mRNA expression. Staining and mRNA expression for ActRIB were undetected in the late-pregnancy group. In summary, the present study demonstrated that the activin-related proteins, βA, βB, and α-inhibin subunits, as much as follistatin and ActRIB and ActRIIA receptors display different patterns of expression regarding time of gesta-rntion in the bovine mammary gland. The modulation of the expression pattern during gestation suggests that activin-related proteins may play a key role in regulating bovine mammary branching morphogenesis and epithelial differentiation.