ABSTRACT
This investigation examined the influence of hormone replacement therapy on plasma leptin concentrations in postmenopausal women and sought to determine if a relationship existed between plasma leptin, the thermoregulatory cytokine interleukin-1 (IL-1), and basal body temperature. Twenty-two women (54-71 years of age) were studied: eight were not taking hormone replacement, seven took oral estrogen only, and seven took oral estrogen plus progestin. Morning oral temperature, plasma leptin concentration, and mononuclear cell secretion of IL-1beta, IL-1 receptor antagonist (IL-1Ra), and soluble IL-1 receptor type II (sIL-1RII) were measured. Plasma leptin concentrations were not affected by hormone replacement therapy, but were inversely related to years since menopause (R = -0.48, P = 0.02) and were proportional to IL-1 activity (the balance of IL-1beta/IL-1Ra secretion, R = 0.69, P = 0.001). Moreover, morning oral temperature was positively related to plasma leptin (P = 0.03), after stratifying by progestin intake. These results support the concept that basal body temperature is regulated by a network of endocrine and immune mediators that are significantly influenced by age.
Subject(s)
Aging/metabolism , Estrogen Replacement Therapy , Leptin/blood , Postmenopause/metabolism , Aged , Aging/immunology , Body Temperature/physiology , Estrogens/administration & dosage , Female , Humans , Interleukin 1 Receptor Antagonist Protein , Interleukin-1/metabolism , Middle Aged , Postmenopause/immunology , Progesterone Congeners/administration & dosage , Receptors, Interleukin-1/metabolism , Receptors, Interleukin-1 Type II , Receptors, Leptin , Sialoglycoproteins/metabolismABSTRACT
Hormone replacement therapy (HRT) reduces the risk for osteoporosis but transiently increases cardiovascular risk for some postmenopausal women. This study investigated the hypothesis that these risks are associated with HRT-induced changes in mononuclear cell secretion of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and associated soluble receptors. Compared to the untreated condition (n=8), estrogen therapy (n=7) and estrogen+progestin therapy (n=7) both caused 2-fold elevations in TNF-alpha secretion. IL-6 secretion was increased (48%, P=0.04) only by estrogen+progestin therapy. Although soluble receptor secretion was not different among groups, soluble TNF receptor type I and IL-6 receptor secretion were inversely related to plasma follicle stimulating hormone (P<0.05). Both therapies reduced plasma osteocalcin (a marker for osteoporosis) by approximately 50% (P<0.002). Plasma C-reactive protein (CRP, a marker for cardiovascular risk) was 3-fold higher in women receiving only estrogen, compared to untreated women (P=0.01), and twice as high as those receiving estrogen+ progestin (P=0.045). Simple linear relationships were not observed between cytokine secretion and these markers, but a significant HRT/TNF-alpha interaction with osteocalcin (P=0.022) and an HRT/IL-6 interaction with CRP (P =0.016) indicated more complex relationships between hormone replacement, cytokine activity, and health risks associated with menopause.
Subject(s)
Interleukin-6/metabolism , Tumor Necrosis Factor-alpha/metabolism , C-Reactive Protein/metabolism , Cytokines/metabolism , Drug Combinations , Estrogens/pharmacology , Estrogens, Conjugated (USP)/pharmacology , Female , Follicle Stimulating Hormone/blood , Hormone Replacement Therapy , Humans , Leukocytes, Mononuclear/metabolism , Medroxyprogesterone Acetate/pharmacology , Osteocalcin/blood , Osteocalcin/metabolism , Postmenopause , Progestins/pharmacology , Receptors, Tumor Necrosis Factor/metabolismABSTRACT
We hypothesized that estradiol treatment would improve vascular dysfunction commonly associated with obesity, hyperlipidemia, and insulin resistance. A sham operation or 17beta-estradiol pellet implantation was performed in male lean and obese Zucker rats. Maximal vasoconstriction (VC) to phenylephrine (PE) and potassium chloride was exaggerated in control obese rats compared with lean rats, but estradiol significantly attenuated VC in the obese rats. Estradiol reduced the PE EC50 in all groups. This effect was cyclooxygenase independent, because preincubation with indomethacin reduced VC response to PE similarly in a subset of control and estrogen-treated lean rats. Endothelium-independent vasodilation (VD) to sodium nitroprusside was similar among groups, but endothelium-dependent VD to ACh was significantly impaired in obese compared with lean rats. Estradiol improved VD in lean and obese rats by decreasing EC50 but impaired function by decreasing maximal VD. The shift in EC50 corresponded to an upregulation in nitric oxide synthase III protein expression in the aorta of the estrogen-treated obese rats. In summary, estrogen treatment improves vascular function in male insulin-resistant, obese rats, partially via an upregulation of nitric oxide synthase III protein expression. These effects are counteracted by adverse factors, such as hyperlipidemia and, potentially, a release of an endothelium-derived contractile agent.
