Pituitary-specific knockout of steroidogenic factor 1.
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 approximately 5% of the weight of wild-type gonads. SF-1 immunoreactivity 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.
Zhao
L
L
Division of Endocrinology, Department of Internal Medicine and Pharmacology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-8857, USA.
Bakke
M
M
Parker
K L
KL
D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology*; D005260:Female; D051717:Fushi Tarazu Transcription Factors; D018398:Homeodomain Proteins; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010053:Ovary / Q000473:pathology; D010903:Pituitary Gland, Anterior / Q000378:metabolism*; D010908:Pituitary Hormones, Anterior / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear; D054339:Steroidogenic Factor 1; D013737:Testis / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology*
D004268:DNA-Binding Proteins; D051717:Fushi Tarazu Transcription Factors; D018398:Homeodomain Proteins; C515057:NR5A1 protein, human; D010908:Pituitary Hormones, Anterior; D018160:Receptors, Cytoplasmic and Nuclear; D054339:Steroidogenic Factor 1; D014157:Transcription Factors; C515058:steroidogenic factor 1, mouse