title: The effects of estradiol and progesterone on reproductive tract atrophy and tissue adrenergic indices in diabetic C57BL/KsJ mice.
abstract: The diabetes-associated changes in tissue norepinephrine (NE) concentrations and related adrenergic receptor types were correlated with changes in blood glucose and serum insulin levels in 8- to 16-week-old C57BL/KsJ-db/db mice relative to corresponding age-matched control (+/?) parameters. In addition, the ability of estradiol and progesterone treatments to modify the diabetes-related adrenergic imbalance was investigated. Tissue (i.e., ovarian, uterine, pancreatic, and adrenal) NE levels were determined by high-performance liquid chromatography and compared with the associated changes in tissue alpha 1,2 and beta-adrenergic membrane receptor populations. All db/db mice exhibited overt hyperglycemia, hyperinsulinemia, and obesity relative to controls between 8 and 16 weeks of age. Tissue NE levels in diabetics were either similar to, or elevated, as compared with those of age-matched controls. Although the alpha 1 and beta receptor populations (except liver) were similar in 16-week-old groups, alpha 2 receptor populations in db/db mice were elevated relative to controls. Chronic estradiol therapy effectively counteracted the diabetes-induced elevations in tissue NE and influenced all adrenergic receptor populations, normalizing both parameters to control levels as well as modifying the hyperglycemia, but not the hyperinsulinemic component, of the diabetes-obesity syndrome in this species. Chronic progesterone treatment was found to be less effective in modulating these systemic and adrenergic parameters in diabetics relative to oil- or estradiol-treated mice. These data demonstrate that a marked modification in tissue adrenergic parameters occur in association with the overt expression of the diabetes mutation in this species. The ability of estradiol treatment to normalize both blood glucose levels and tissue adrenergic parameters in C57BL/KsJ-db/db mice indicates that a direct association between systemic and cellular counter-regulating influences, relative to the severity of the Type II diabetic condition, exists in this species. The therapeutic correction of these metabolic problems by ovarian steroid hormones suggests the existence of a causal relationship between cellular glucose homeostasis and steroid action in the diabetic model.
authors: Department of Anatomy, Cleveland Research Laboratory, Kansas City, Missouri 64131.
authors: D R
authors: DR
authors: Garris
mesh_terms: D000818:Animals; D001284:Atrophy; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006321:Heart / Q000187:drug effects; D007328:Insulin / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D010053:Ovary / Q000187:drug effects / Q000378:metabolism; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism; D011374:Progesterone / Q000494:pharmacology*; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D014599:Uterus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*
chemical_list: D001786:Blood Glucose; D007328:Insulin; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D011374:Progesterone; D004958:Estradiol; D009638:Norepinephrine