Pituitary hypoplasia and decreased GnRH neurogenesis in Sox2-deficient Mice

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• Dr. Juan Pedro Martinez-Barbera. UCL Institute of Child Health
• Thursday 24 January 2013, 16:00-17:00
• Hodgkin Huxley Seminar Room, Physiology Building, Downing Site.

If you have a question about this talk, please contact Annabel Griffiths.

SOX2 haploinsufficiency causes hypopituitarism in humans and specifically isolated gonadotrophin deficiency (hypogonadotrophic hypogonadism, HH). Here, we have used a conditional approach in mice to investigate the pathogenesis of these defects. First, we demonstrate that absence of SOX2 in the developing Rathke’s pouch (RP) of Hesx1Cre/+;Sox2fl/fl embryos leads to severe anterior lobe hypoplasia with a drastic reduction of POU1F1 expression and severe disruption of somatotroph and thyrotroph differentiation. In contrast, corticotrophs, rostral-tip POU1F1 -independent thyrotrophs and, interestingly, lactotrophs and gonadotrophs are less affected. Secondly, we show that SOX2 is required for normal proliferation of RP periluminal progenitors and its absence results in failure to yield a sufficiently large pool of precursors for all cell lineages of the anterior pituitary. Accordingly, differentiated cells derived from precursors exiting cell cycle at early stages (i.e. corticotrophs, rostral-tip thyrotrophs and gonadotrophs) are generated, whilst hormone-producing cells originating from late-born precursors (i.e. somatotrophs and POU1F1 -dependent thyrotrophs) are severely impaired. Finally, we demonstrate that two previously characterised patients with SOX2 haploinsufficiency and associated HH have a measurable response to GnRH stimulation, suggesting that it is not the absence of gonadotroph differentiation, but rather their deficient hypothalamic stimulation that underlies the typical HH.

This talk is part of the Foster Talks series.

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