Reproductive function is dependent upon the coordinate regulation of a group of adenohypophysial and neurohypophysial hormones. In this proposal, our focus will be primarily limited to central catecholaminergic, neuropeptide tyrosine (NPY) and inhibin-family related modulation of gene expression and secretion of gonadotropin releasing hormone (GNRH) and oxytocin (OT). The catecholamines, norepinephrine (NE) and epinephrine (EPI), as well as NPY, which may arise from non-catecholaminergic fibers or may be co-secreted from catecholamine-containing terminals, exert gonadal steroid dependent actions on GNRH secretion and content. This effect is stimulatory in the presence of estrogen and inhibitory in its absence. In the first portion of this proposal, we will examine the relationships existing between catecholamine and NPY secretion in relation to GNRH and LH secretion, as well as GNRH expression in neuroendocrine neurons. In the second part of this proposal, we will clarify the actions of centrally produced inhibin-beta-like peptides on the GNRH and magnocellular OT systems. Inhibin-beta-like peptides are produced in cells of the caudal nucleus tractus solitarius which project to GnRH-, OT-, and CRF-rich containing cells in the hypothalamus. Recent studies from our laboratory imply participation of this pathway in facilitation of OT secretion in response to suckling and certain stressors. Preliminary evidence suggests that activation of this pathway during lactation may coordinate increased OT expression and secretion, reduction of GNRH expression and secretion, as well as elevated adrenal steroid secretion leading to a pro-lactational environment. Thus we will focus upon delineating the actions of activin, an I-beta-homodimer, on expression and secretion of GNRH and OT. Pharmacological actions of exogenous activin will be contrasted with effects correlated with stimulation of endogenous activin release. In addition, the ontogeny of the I-beta-system will be examined in relation to ontogeny and maturation of the GNRH and OT systems.
| 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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