A HOT-SPOT IN THE PIT-1 GENE RESPONSIBLE FOR COMBINED PITUITARY-HORMONE DEFICIENCY - CLINICAL AND MOLECULAR CORRELATES

Pit-1 is a member of the POU family of transcription factors regulatin g mammalian development. Pit-1 is thought to be the major cell-specifi c activator of both the somatotrophs and lactotrophs in the anterior p ituitary. When bound to DNA, Pit-1 activates GH and PRL gene expressio n. Pit-1 is also important for hormonal regulation of the PRL and TSH- beta genes by TRH and cAMP. We studied two unrelated patients with GH, PRL, and TSH deficiencies. Both patients have the same point mutation in the POU homeodomain of the Pit-1 gene (R271W). Patient 1 was studi ed as an adult and had combined deficiencies of GH, PRL, and TSH. Pati ent 2, who was studied in infancy, also had GH and PRL deficiencies, b ut had low thyroid hormone levels with a measurable basal level of TSH and a delayed response of TSH to TRH. Consequently, the current descr iption of Pit-1 gene mutations leading to complete GH, PRL, and TSH de ficiencies needs to be expanded to GH and PRL deficiencies associated with a compromise of the thyrotroph's ability to synthesize TSH.