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We examined effects of 17[beta]-estradiol ([E.sub.2]) on human vascular smooth muscle cell (VSMC) proliferation under normal (5 mmol/l) and high (25 mmol/l) glucose concentrations. Platelet-derived growth factor (PDGF) BB (20 ng/ml)-induced increases in DNA synthesis and proliferation were greater in high than normal glucose concentrations; the difference in DNA synthesis was abolished by a protein kinase C (PKC)-[beta] inhibitor, LY-379196 (30 nmol/l). Western blotting showed that PKC-[[beta].sub.1] protein increased in cells exposed to high glucose, whereas PKC-[alpha] protein and total PKC activity remained unchanged, compared with normal glucose cultures. In normal glucose, [E.sub.2] (1-100 nmol/l) inhibited PDGF-induced DNA synthesis by 18-37% and cell proliferation by 16-22% in a concentration-dependent manner. The effects of [E.sub.2] were blocked by the estrogen receptor (ER) antagonist ICI-182780, indicating ER dependence. In high glucose, the inhibitory effect of [E.sub.2] on VSMC proliferation was abolished but was restored in the presence of the PKC-[beta] inhibitor LY-379196. Thus high glucose enhances human VSMC proliferation and attenuates the antiproliferative effect of [E.sub.2] in VSMC via activation of PKC-[beta]. high glucose; estrogen; proliferation; smooth muscle cells; protein kinase C-[beta]

Experiments were performed to investigate the effects of estrogen on the responses to stress of the adrenocorticotropic hormone (ACTH), cortisol, epinephrine (Epi) and norepinephrine (NE) in ovariectomized ewes. In particular, the responses to the audiovisual and hypoglycemic stress in the follicular and luteal phases of the estrous cycle were described. The findings suggest that the administration of estrogen attenuated the glucocorticoid reaction to audiovisual and hypoglycemic stress, while the responses of ACTH, Epi and NE were heightened during the luteal phase.

Examines the effects of 17 β-estradiol on human vascular smooth muscle cell (VSMC) proliferation under normal and high glucose concentrations. Assays of cell proliferation; Analysis of protein kinase C (PKC) activity; Involvement of PKC-β in the stimulatory effect of high glucose on VSMC proliferation.