Context: It is unclear whether the pattern of GH delivery to peripheral tissues has important effects. Objective: The aim of the study was to compare the effects of pulsatile vs. continuous administration of GH upon metabolic and IGF-I parameters in obese subjects. Setting: The study was conducted at the General Clinical Research Center at the University of Michigan Medical Center. Participants: Four men and five women with abdominal obesity (body mass index, 33 3 kg/m; body fat, 40 3%) participated in the study. Intervention: GH (0.5 mg/m d) was given iv for 3 d as: 1) continuous infusion (C); and 2) pulsatile boluses (P) (15% of the dose at 0700, 1300, and 1800 h and 55% at 2400 h). These trials were preceded by a basal period (B) when subjects received normal saline. Main Outcome Measures: Rate of lipolysis and hepatic glucose production were evaluated using stable isotope tracer techniques. The composite index of insulin sensitivity (Matsuda index) was assessed using oral glucose tolerance test. Results: The increase in plasma IGF-I concentrations was greater (P 0.05) with continuous GH infusion (211 31, 423 38, and 309 34 g/liter for B, C, and P, respectively). Muscle IGF-I mRNA was significantly increased (P 0.05) only after the continuous GH infusion (1.2 0.4, 4.4 1.3, and 2.3 0.6 arbitrary units, for B, C, and P, respectively). Only pulsatile GH augmented the rate of lipolysis (4.1 0.3, 4.8 0.7, and 7.1 1.1 mol/kg min for B, C, and P, respectively). GH had no effect on hepatic glucose production, but both modes of GH administration were equally effective in impairing insulin sensitivity. Conclusion: These findings indicate that, in obese subjects, discrete components of GH secretory pattern may differentially affect IGF-I generation and lipolytic responses. Vascular Endothelial Estrogen Receptor Is Modulated by Estrogen Status and Related to Endothelial Function and Endothelial Nitric Oxide Synthase in Healthy Women Kathleen M. Gavin, Douglas R. Seals, Annemarie E. Silver, and Kerrie L. Moreau (J Clin Endocrinol Metab, published June 9, 2009, 10.1210/jc.2009-0278) ABSTRACT Context and Objective: Estrogen receptor (ER ), a potent transcription factor expressed in vascular endothelial cells, plays a key role in regulating vascular function and health. We determined whether vascular endothelial cell expression of ER is influenced by estrogen status and is related to vascular endothelial function in healthy women. Methods: ER protein expression was measured (quantitative immunofluorescence) in endothelial cells from peripheral veins of 16 healthy, premenopausal women during the early follicular (EF) and late follicular (LF) phases of the menstrual cycle and 17 estrogen-deficient postmenopausal women. Endothelial-dependent dilation (EDD; brachial artery flow-mediated dilation) and endothelial nitric oxide synthase (eNOS) expression and activation were also measured in a subgroup of women. Results: In premenopausal women (n 10), ER expression was 30% lower (P 0.001) during the EF (low estrogen) compared with the LF (high estrogen) phase of the menstrual cycle. In postmenopausal women, ER expression was 33% lower (P 0.001) compared with the LF phase of the menstrual cycle in premenopausal women. ER expression was strongly related (r 0.67; P 0.001) to EDD, which was reduced in postmenopausal women. ER abundance was positively related to expression of eNOS (r 0.54; P 0.009; n 21) and ser1177 phosphorylated eNOS (r 0.59; P 0.006; n 20). Conclusions: These results provide the first evidence that expression of ER in vascular endothelial cells is modulated by estrogen status and may be a key determinant of vascular endothelial function in healthy preand postmenopausal women. ER expression may influence vascular endothelial function in women by affecting protein levels and activation of eNOS. 542 Abstracts Translational Highlights from JCEM Endocrine Reviews, August 2009, 30(5):536–543Context and Objective: Estrogen receptor (ER ), a potent transcription factor expressed in vascular endothelial cells, plays a key role in regulating vascular function and health. We determined whether vascular endothelial cell expression of ER is influenced by estrogen status and is related to vascular endothelial function in healthy women. Methods: ER protein expression was measured (quantitative immunofluorescence) in endothelial cells from peripheral veins of 16 healthy, premenopausal women during the early follicular (EF) and late follicular (LF) phases of the menstrual cycle and 17 estrogen-deficient postmenopausal women. Endothelial-dependent dilation (EDD; brachial artery flow-mediated dilation) and endothelial nitric oxide synthase (eNOS) expression and activation were also measured in a subgroup of women. Results: In premenopausal women (n 10), ER expression was 30% lower (P 0.001) during the EF (low estrogen) compared with the LF (high estrogen) phase of the menstrual cycle. In postmenopausal women, ER expression was 33% lower (P 0.001) compared with the LF phase of the menstrual cycle in premenopausal women. ER expression was strongly related (r 0.67; P 0.001) to EDD, which was reduced in postmenopausal women. ER abundance was positively related to expression of eNOS (r 0.54; P 0.009; n 21) and ser1177 phosphorylated eNOS (r 0.59; P 0.006; n 20). Conclusions: These results provide the first evidence that expression of ER in vascular endothelial cells is modulated by estrogen status and may be a key determinant of vascular endothelial function in healthy preand postmenopausal women. ER expression may influence vascular endothelial function in women by affecting protein levels and activation of eNOS. 542 Abstracts Translational Highlights from JCEM Endocrine Reviews, August 2009, 30(5):536–543