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Estrogenic stimulation of ovarian follicular maturation in diabetes (db/db) mutant mice: restoration of euglycemia prevents hyperlipidemic cytoatrophy.

Abstract：

: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.

journal_name

Cell Tissue Res

journal_title

Cell and tissue research

authors

Garris DR

doi

10.1007/s00441-004-0967-6

keywords:

subject

Has Abstract

pub_date

2004-11-01 00:00:00

pages

365-73

issue

eissn

0302-766X

issn

1432-0878

journal_volume

318

pub_type

杂志文章

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Estrogenic stimulation of ovarian follicular maturation in diabetes (db/db) mutant mice: restoration of euglycemia prevents hyperlipidemic cytoatrophy.