期刊
MOLECULAR AND CELLULAR ENDOCRINOLOGY
卷 185, 期 1-2, 页码 27-32出版社
ELSEVIER SCI IRELAND LTD
DOI: 10.1016/S0303-7207(01)00621-9
关键词
gonadotrope; Cre rccombinase; tissue-specific knockout
资金
- NIDDK NIH HHS [DK 54480] Funding Source: Medline
Knockout mice lacking the orphan nuclear receptor steroidogenic factor 1 (SF-1) revealed its essential roles at multiple levels of endocrine development and function. These SF-1 knockout mice lacked adrenal glands and gonads, thereby manifesting adrenal insufficiency and sex reversal of their internal and external genitalia. Their pituitary gonadotropes failed to express several markers of normal differentiated function, and they lacked a specific hypothalamic nucleus, the ventromedial hypothalamic nucleus (VMH). Using the Cre-loxP system, we generated mice whose gene encoding SF-1 was inactivated specifically in the anterior pituitary. These pituitary-specific SF-1 knockout mice were sterile and never matured sexually. Their gonads weighed only similar to 5% of the weight of wild-type gonads. SF-1 immuno reactivity was absent in the anterior pituitary but was unaffected in the adrenal cortex, validating the selectivity of the gene targeting strategy. Consistent with an important role of SF-1 in gonadotropes, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were markedly decreased in the pituitary-specific SF-1 knockout mice. The pituitary-specific SF-1 knockout mice are a novel genetic model of hypogonadotropic hypogonadism and establish essential roles of SF-1 in gonadotropin expression. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.
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