Bakke M, Zhao L, Parker K L
Department of Internal Medicine, Division of Endocrinology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75235-8857, USA.
Mol Cell Endocrinol. 2001 Jun 20;179(1-2):33-7. doi: 10.1016/s0303-7207(01)00468-3.
Targeted gene disruption has produced knockout mice lacking the orphan nuclear receptor steroidogenic factor 1 (SF-1). These SF-1 knockout mice lacked adrenal glands and gonads, resulting in adrenocortical insufficiency and sex reversal of their internal and external genitalia. They also had impaired expression of pituitary gonadotropins and agenesis of the ventromedial hypothalamic nucleus (VMH), confirming roles of SF-1 at multiple levels of the hypothalamic-pituitary-steroidogenic tissue axis. Using the Cre-loxP system, we now have generated mice in which SF-1 is inactivated selectively in the anterior pituitary. These pituitary-specific SF-1 knockout mice were sterile and failed to exhibit sexual maturation. Histologically, their gonads were markedly hypoplastic, weighing only approximately 5% of the gonads of wild-type mice. Consistent with an important role of SF-1 in gonadotropes, there were no cells in the pituitary gland that expressed either follicle-stimulating hormone (FSH) or luteinizing hormone (LH). These pituitary-specific SF-1 knockout mice are a novel genetic model of hypogonadotropic hypogonadism and establish essential roles of SF-1 in gonadotropin expression.
靶向基因破坏已产生缺乏孤儿核受体类固醇生成因子1（SF-1）的基因敲除小鼠。这些SF-1基因敲除小鼠缺乏肾上腺和性腺，导致肾上腺皮质功能不全以及内外生殖器的性反转。它们还存在垂体促性腺激素表达受损和腹内侧下丘脑核（VMH）发育不全的情况，这证实了SF-1在下丘脑-垂体-类固醇生成组织轴多个水平上的作用。利用Cre-loxP系统，我们现已培育出SF-1在前脑垂体中被选择性灭活的小鼠。这些垂体特异性SF-1基因敲除小鼠不育且未能表现出性成熟。组织学检查显示，它们的性腺明显发育不全，重量仅约为野生型小鼠性腺的5%左右。与SF-1在促性腺激素细胞中的重要作用一致，垂体中没有表达促卵泡激素（FSH）或促黄体生成素（LH）的细胞。这些垂体特异性SF-1基因敲除小鼠是低促性腺激素性性腺功能减退的新型遗传模型，并确立了SF-1在促性腺激素表达中的重要作用。
