The PROP1 gene is essential for normal gonadotropin production in both humans and mice. Transgenic mice that over-express 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 gonadotropin releasing hormone 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 EGR1, NR5A1, GATA2, TBX19, and NR0B1, or the transforming growth factor (TGF) pathway members including activin, inhibin, and activin receptors. Thus, over-expression 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.