Approaches to define the role of SF-1 at different levels of the hypothalamic-pituitary-steroidogenic organ axis.
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.
Bakke
M
M
Department of Internal Medicine, Division of Endocrinology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75235-8857, USA.
Zhao
L
L
Parker
K L
KL
D000311:Adrenal Glands / Q000002:abnormalities; D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000172:deficiency; D051717:Fushi Tarazu Transcription Factors; D006065:Gonadotropins, Pituitary / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D006066:Gonads / Q000002:abnormalities; D018398:Homeodomain Proteins; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology*; D007986:Luteinizing Hormone / Q000172:deficiency; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010913:Pituitary-Adrenal System / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear; D054339:Steroidogenic Factor 1; D014157:Transcription Factors / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*
D004268:DNA-Binding Proteins; D051717:Fushi Tarazu Transcription Factors; D006065:Gonadotropins, Pituitary; D018398:Homeodomain Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D054339:Steroidogenic Factor 1; D014157:Transcription Factors; C515058:steroidogenic factor 1, mouse; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone