Role of prophet of Pit1 (PROP1) in gonadotrope differentiation and puberty.
The prophet of Pit1 (PROP1) gene is essential for normal gonadotropin production in both humans and mice. Transgenic mice that overexpress PROP1 in gonadotropes and thyrotropes have transient hypogonadotropic hypogonadism and increased risk of pituitary adenomas. Here we report a temporal study of pituitary gonadotrope terminal differentiation and hypogonadism, delayed onset of puberty, and transient growth insufficiency in the transgenic males. The Prop1 transgenic mice recover from their abnormalities and exhibit normal size and fertility at 3 months. The relatively normal expression pattern of GnRH receptor (Gnrhr) suggests that the pituitary gonadotrope cell lineage is appropriately specified, but the ability to synthesize LH and FSH is impaired by excess PROP1. We report no obvious abnormalities in expression of the transcription factors early growth response 1, NR5A1, GATA2, TBX19, and NR0B1, or the TGFbeta pathway members including activin, inhibin, and activin receptors. Thus, overexpression of PROP1 may influence gonadotrope development by a novel mechanism. Microarray analysis identified the inhibitory transmembrane receptor gene Klrg1 and the protease gene Prss28 as candidates for involvement in this process. We hypothesize that variation in PROP1 expression could affect the growth spurt and the onset of puberty in humans.
Vesper
Amanda H
AH
Department of Human Genetics, University of Michigan, Ann Arbor, 48109-0618, USA.
Raetzman
Lori T
LT
Camper
Sally A
SA
D000818:Animals; D002454:Cell Differentiation; D005260:Female; D005640:Follicle Stimulating Hormone / Q000096:biosynthesis; D020869:Gene Expression Profiling; D006130:Growth Disorders / Q000209:etiology; D018398:Homeodomain Proteins / Q000502:physiology*; D037181:Lectins, C-Type; D007986:Luteinizing Hormone / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010903:Pituitary Gland, Anterior / Q000196:embryology* / Q000378:metabolism; D011971:Receptors, Immunologic / Q000502:physiology; D012697:Serine Endopeptidases / Q000502:physiology; D012741:Sexual Maturation
D018398:Homeodomain Proteins; C451496:Klrg1 protein, mouse; D037181:Lectins, C-Type; C102134:Prophet of Pit-1 protein; D011971:Receptors, Immunologic; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; C436412:Prss28 protein, mouse; D012697:Serine Endopeptidases