Structural, metabolic and endocrine analysis of the diabetes (db/db) hypogonadal syndrome:: relationship to hypophyseal hypercytolipidemia

被引:9
作者
Garris, DR
Garris, BL
Novikova, L
Lau, YS
机构
[1] Univ Missouri, Sch Biol Sci, Div Cell Biol & Biophys, Kansas City, MO 64110 USA
[2] Univ Missouri, Sch Med, Kansas City, MO 64110 USA
[3] Univ Missouri, Sch Pharm, Div Pharmacol, Kansas City, MO 64110 USA
关键词
female reproductive tract; pituitary-ovarian axis; hypogonadal syndrome; diabetes (db/db) mutation; hypercytolipidemia; diabetes-obesity syndrome; gonadal steroids; mouse; (C57BL/KsJ; female);
D O I
10.1007/s00441-004-1021-4
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Expression of the diabetes (db/db) mutation in C57BL/KsJ mice results in functional suppression of the female pituitary-gonadal axis accompanied by premature utero-ovarian cytolipoatrophy. Cellular gluco- and lipo-metabolic disturbances promoted by the db/db systemic hyperglycemic-hyperinsulinemic state suppress pituitary gonadotropin release in response to gonadotropin-releasing hormone and gonadal steroid stimulation and results in a hypogonadal-infertility syndrome. Adult female C57BL/KsJ control (+/+ and +/? genotypes) and db/db littermates were monitored for associations in systemic and cellular alterations in luteinizing hormone (LH), follicle-stimulating hormone (FSH), gonadal steroid (binding) levels, and pituitary glucometabolic indices associated with db/db-enhanced lipid imbibition and cytostructural disruption. Obesity, hyperglycemia, and hyperinsulinemia characterized all db/db mutants relative to controls. Serum and pituitary progesterone and estradiol concentrations were suppressed in db/db mutants, in association with serum LH and FSH levels, but not with pituitary LH and FSH concentrations, which were comparable between groups. Pituitary insulin receptor binding and glucose utilization rates were suppressed in db/db groups relative to +/? indices. Structural and cytochemical analysis of anterior (AP), intermediate (IL), and neuro-(NP) hypophyseal lobes demonstrated prominent hypercytolipidemia in db/db mutants relative to controls. Prominent cytolipidemia was localized within well-granulated basophilic gonadotrophs and within IL and NP pituicytes. Vasolipidemia and interstitial cytoadiposity were prominent throughout all db/db pituitary lobes. Thus, disturbances associated with pituitary hypercytolipidemia are functional components of the expressed diabetes-associated hypogonadal syndrome in db/db mutants. Progressive alterations in hypophyseal cytoarchitecture are correlated with suppression of pituitary metabolic and endocrine indices, alterations that contribute to functional disruption of the pituitary-hypogonadal axis in C57BL/KsJ-db/db mice.
引用
收藏
页码:501 / 512
页数:12
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