Activin and inhibin are gonadal proteins that alter both pituitary and ovarian function. The work presented in the present proposal represents an extension of our previous studies of the effects of, and the role played by these proteins. We have observed that the peripheral administration of activin increased GnRH mRNA levels in the hypothalamus.
Under Specific Aim 1, we will determine whether inhibin also alters GnRH gene expression; whether the effect of activin (and possibly inhibin) on GnRH transcripts are mediated by sex steroids; whether changes in brain GnRH levels are accompanied by altered release of the peptide from the median eminence; and whether endogenous opiates play a role in these effects. We will also investigate the role of activin during the estrous cycle and during the early increase in gonadotropin levels caused by gonadectomy, by blocking activin with specific neutralizing antibodies of the ligand binding domain. These experiments will address as yet unexplored aspects of the role and effects of inhibin/activin.

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Salk Institute for Biological Studies
La Jolla
United States
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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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