| First Author | Garris DR | Year | 2004 |
| Journal | Cell Tissue Res | Volume | 318 |
| Issue | 2 | Pages | 365-73 |
| PubMed ID | 15503160 | Mgi Jnum | J:105171 |
| Mgi Id | MGI:3614249 | Doi | 10.1007/s00441-004-0967-6 |
| Citation | Garris DR (2004) Estrogenic stimulation of ovarian follicular maturation in diabetes (db/db) mutant mice: restoration of euglycemia prevents hyperlipidemic cytoatrophy. Cell Tissue Res 318(2):365-73 |
| abstractText | The diabetes (db/db) mutation (leptin-receptor defect) induces a hyperglycemic-hyperinsulinemic endometabolic environment that promotes hypercytolipidemic ovarian involution in C57BL/KsJ mice, resulting in reproductive sterility and eventual organoatrophy. The effectiveness of low-dose (1.0 microg/sc/3.5 day intervals), 17- beta-estradiol therapy (E2-HRx), initiated prior to expression of the overt diabetes-obesity syndrome (DOS), on preventing female ovarian follicular cytolipid atrophy was evaluated by analysis of cytochemical, endocrine, and tissue lipo-metabolic indices relative to oil-vehicle treated control (+/?) and (db/db) groups. Chronic low-dose E2-HRx moderated DOS-induced trends in (db/db) groups, maintaining lowered body weights, and systemic euglycemia while stimulating ovarian weight indices. E2-HRx prevented the dramatic hypercytolipidemic condition associated with ovarian follicular involution in (db/db) mice, as evidenced by progressive viable follicular maturation, cytomorphometric analysis of tertiary follicular development, and pre-luteinization indices with diminished follicular atresia rates. The coincident stimulation of tissue lipoprotein lipase and acetyl CoA carboxylase activities in (db/db) ovarian compartments, under persistent hyperinsulinemic influences, indicated that E2-HRx effectively moderated both the structural and hyperlipometabolic consequences of DOS from promoting (db/db)-associated reproductive organoatrophy. Thus, the patho-reproductive alterations induced by the (db/db) mutation can be moderated through low-dose steroidal therapy, the efficacy of which is suspected to occur by steroid-specific nuclear transcription or post-insulin receptor modulation of gluco-metabolic cascades in reproductive target cells. |
