Inhibins and activins were initially recognized as gonadal protein hormones which modulate follicle stimulating hormone (FSH) production.by the anterior pituitary gland. During the last grant period, these proteins have been characterized as alpha-beta-hetero- and beta-beta homodimers related to the TGF-0 family of growth and differentiation factors. Inhibin and activin subunits and their mRNA's are broadly distributed and have often mutually opposing actions on multiple tissues where they are hypothesized to play a variety of types of roles.as hormonal, paracrine and autocrine regulators of cellular function and proliferation.
The aims of this project are to examine this hypothesis in the pituitary, placenta and brain. With improved immunologic and other tools, the chemical nature of the inhibin/activin-like proteins will be defined in those tissues shown to express inhibin/activin subunit mRNA's and the regulation of local production of inhibin and activin will be examined. The actions of exogenous inhibin and activin as well as neutralizing antibodies will be tested in vitro and in concert with other projects in vivo. Transgenic mice overexpressing the PA subunit and presumably activin will be developed and evaluated. The cellular actions of activin and inhibin along with the nature and regulation of the activin receptor will be explored. The proposed studies will improve our understanding of this new protein family and their roles in the regulation of reproduction.
| Muenster, Uwe; Korupolu, Radhika; Rastogi, Ratindra et al. (2011) Antagonism of activin by activin chimeras. Vitam Horm 85:105-28 |
| Kim, Meejung; Choe, Senyon (2011) BMPs and their clinical potentials. BMB Rep 44:619-34 |
| Looyenga, Brendan D; Wiater, Ezra; Vale, Wylie et al. (2010) Inhibin-A antagonizes TGFbeta2 signaling by down-regulating cell surface expression of the TGFbeta coreceptor betaglycan. Mol Endocrinol 24:608-20 |
| Valera, Elvira; Isaacs, Michael J; Kawakami, Yasuhiko et al. (2010) BMP-2/6 heterodimer is more effective than BMP-2 or BMP-6 homodimers as inductor of differentiation of human embryonic stem cells. PLoS One 5:e11167 |
| Isaacs, Michael J; Kawakami, Yasuhiko; Allendorph, George P et al. (2010) Bone morphogenetic protein-2 and -6 heterodimer illustrates the nature of ligand-receptor assembly. Mol Endocrinol 24:1469-77 |
| Hassold, Terry; Hunt, Patricia (2009) Maternal age and chromosomally abnormal pregnancies: what we know and what we wish we knew. Curr Opin Pediatr 21:703-8 |
| Wiater, Ezra; Lewis, Kathy A; Donaldson, Cynthia et al. (2009) Endogenous betaglycan is essential for high-potency inhibin antagonism in gonadotropes. Mol Endocrinol 23:1033-42 |
| Cheng, Edith Y; Hunt, Patricia A; Naluai-Cecchini, Theresa A et al. (2009) Meiotic recombination in human oocytes. PLoS Genet 5:e1000661 |
| Ciarmela, Pasquapina; Wiater, Ezra; Smith, Sean M et al. (2009) Presence, actions, and regulation of myostatin in rat uterus and myometrial cells. Endocrinology 150:906-14 |
| Blount, Amy L; Vaughan, Joan M; Vale, Wylie W et al. (2008) A Smad-binding element in intron 1 participates in activin-dependent regulation of the follistatin gene. J Biol Chem 283:7016-26 |
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