Previous research indicates the presence of a feedback inhibitor of lactation (FIL) in milk (Peaker and Wilde, 1996). Recently, tryptophan hydroxylase I (TPH1), the rate-limiting enzyme in serotonin (5-HT) biosynthesis, was identified in the mouse mammary gland and to be regulated by prolactin (PRL). Furthermore, 5-HT was present in rodent milk and addition of 5-HT to in vitro mammary cultures and in vivo administration of 5-HT to lactating mice reduced milk protein synthesis. Studies were conducted to determine the presence of the enzymatic machinery necessary to produce 5-HT in the bovine mammary gland, the presence of specific 5-HT receptors within the bovine mammary gland, the effects of 5-HT and non-selective and selective receptor antagonists on milk protein gene expression in cultures of primary bovine mammary epithelial cells (BMEC), and to determine the effects of intra-mammary infusions of 5-HT and a non-selective 5-HT receptor antagonist on milk production and composition in lactating dairy cows. Tryptophan hydroxylase I, aromatic amino acid decarboxylase (AADC) and the 5-HT reuptake transporter (SERT) were detected in lactating bovine mammary tissue by qRT-PCR and immunohistochemical staining. Additionally, mRNA for the 5-HT 1B, 2A, 2B, 4 and 7 receptors were detected in bovine mammary tissue as well as BMEC by qRT-PCR and in situ hybridization. Tryptophan hydroxylase I mRNA is in BMEC and up-regulated by PRL. Serotonin down-regulates milk protein gene expression but has not apparent effects on apoptosis and methysergide, ritanserin, SB-224289, and pimozide (receptor antagonists) increased milk protein gene expression in BMEC. Intra-mammary 5-HT infusions decreased overall milk yield in late-lactating dairy cows by 11.1%. Intra-mammary infusions of METH increased overall milk yield by 10.9%. In conclusion, the enzymatic machinery for 5-HT biosynthesis and uptake, as well as receptors involved 5-HT signaling are present in the bovine mammary gland. Furthermore, 5-HT appears to be a FIL in the bovine, but further research regarding its cellular mechanism of action and the location of its receptor populations should be conducted.

Establishing adequate muscle mass is essential for metabolic health. Fetuses with intrauterine growth restriction (IUGR) are born with less muscle mass than appropriate for gestational age infants and never fully recover, as those born IUGR demonstrate persistent reductions in lean body mass in adulthood. Consequently, children and adults with IUGR have an increased risk of developing type 2 diabetes, obesity, and other complications associated with the metabolic syndrome. In order to better understand the in utero programming paradigm of IUGR on skeletal muscle growth and metabolism, we isolated satellite cells from one-month-old lambs and examined their function because of their role in muscle growth. In this series of experiments, we establish a differentiation protocol and show that satellite cells grown on Matrigel (P ≤ 0.05) and in the presence of a TGFβ inhibitor (P ≤ 0.05) have increased fusion events after 3 - 4 days of differentiation. Importantly we found that differentiation of IUGR satellite cells, measured by percent fusion, was greater than controls (P ≤ 0.05). However this difference was lost when cultures were exposed to a TGFβ inhibitor for 24 hours (P > 0.05). Using our optimized differentiation protocol to produce myotubes, we measured insulin-stimulated glucose uptake. IUGR myotubes were less responsive to insulin compared to controls (P < 0.01). These findings demonstrate for the first time that satellite cells from IUGR lambs exhibit disturbed glucose metabolism and differentiation capacity, which indicates that satellite cells become programmed by conditions associated with IUGR.

Thesis (M. S.)--Oklahoma State University, 2006. / Vita. Includes bibliographical references.

Thesis (M. S.)--Oklahoma State University, 2006. / Vita. Includes bibliographical references.

Thesis (M. S.)--Oklahoma State University, 2006. / Vita. Includes bibliographical references.

Thesis (M. S.)--Oklahoma State University, 2006. / Vita. Includes bibliographical references.

Thesis (M.S.)--Oklahoma State University, 2009. / Vita. Includes bibliographical references.

Thesis (M.S.)--Rutgers University, 2009. / "Graduate Program in Nutritional Sciences." Includes bibliographical references (p. 47-51).

Thesis (M.S.)--Oklahoma State University, 2009. / Vita. Includes bibliographical references.

Thesis (M.S.)--Oklahoma State University, 2009. / Vita. Includes bibliographical references.