Effects of estradiol and progesterone on diabetes-associated utero-ovarian atrophy in C57BL/KsJ (db/db) mutant mice.
The modulating effects of estradiol (E: 1 microgram/3.5 days) and progesterone (P: 2 mg/3.5 days) on the obesity and hyperinsulinemic and hyperglycemic components of the diabetes-obesity syndrome in female C57BL/KsJ (db/db) mice, which includes cellular atrophy and adiposity in the reproductive tract, were examined and compared to corresponding control (+/?) parameters. All control and diabetic mice received oil (vehicle control), E, or P treatments starting at 4 weeks of age. Body weight, serum insulin levels, blood glucose concentrations, and utero-ovarian lipoprotein lipase activities were analyzed at 8 and 16 weeks of age and related to the ultrastructural changes in the steroid-sensitive uterine epithelium during the treatment period. Neither E nor P had any effect on body weights in (+/?) or (db/db) mice. The pronounced diabetes-associated elevation in serum insulin levels was enhanced by E, and suppressed by P, in 16-week-old (db/db) mice as compared with controls. By 16 weeks of age, the E therapy normalized blood glucose levels in diabetic mice to control levels, whereas P was ineffective in modulating the hyperglycemia. The reduction in blood glucose levels in E-treated diabetic mice correlated temporally with the return of normal intracellular structure including the disappearance of intracellular lipid vacuoles characteristic of uterine epithelium cells of (db/db) mice. The diabetes-induced rise in utero-ovarian lipoprotein lipase activity was normalized by P-therapy. The reduction in utero-ovarian lipoprotein lipase activity coincided temporally with the demonstrated intracellular reorganization in (db/db) reproductive tract tissues.(ABSTRACT TRUNCATED AT 250 WORDS)
Garris
D R
DR
Department of Anatomy/Division of Basic Sciences, Cleveland Research Laboratory, Kansas City, Missouri 64131.
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D007328:Insulin / Q000097:blood; D008071:Lipoprotein Lipase / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D009765:Obesity / Q000150:complications; D010053:Ovary / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D011374:Progesterone / Q000494:pharmacology*; D013577:Syndrome; D014599:Uterus / Q000187:drug effects / Q000201:enzymology / Q000473:pathology
D001786:Blood Glucose; D007328:Insulin; D011374:Progesterone; D004958:Estradiol; D008071:Lipoprotein Lipase