Table 2.

Pituitary Transcription Factors

Family, Gene	Human disease	Pituitary Function	Ref. (^*)
Paired homeo
PITX1	Congenital club foot, polydactyly, Liebenberg syndrome (homeotic arm to leg transformation)	Modest, overlaps with PITX2	^{88, 221-223}
PITX2	Rieger Syndrome, Eyes, teeth, umbilicus	Rathke’s pouch expansion	^{48, 224}
HESX1	Septo-optic dysplasia, mild to severe hypopituitarism	Affects midline and pituitary growth	⁴⁷
PROP1	Evolving hypopituitarism	Silencing HESX1, OTX2 and Activating NOTCH2 and POU1F1	^{47, 55, 78}
PAX6	Various eye and optic nerve anomalies	Increased growth, expansion of TSH cells at expense of GH and LH	^225-227
PAX7	Rhabdomyosarcoma 2, alveolar	Chromatin remodeling for selecting melanotrope fate	^{77, 228}
Pou homeo
POU1F1 (Pit1)	Hypopituitarism	Signature factor for somatotropes, lactotropes and thyrotropes	^{62, 229}
POU5F1 (Oct4)	Sarcoma if fused with EWS (KO mice die at gastrulation)	Pituitary stem cell marker	^{155, 230}
OTX1	Not known (Critical role in head development)	Expressed in pituitary postnatally. Delayed growth and puberty. Functional overlap with OTX1 and EMX1, 2 in early head development.	⁹²
OTX2	Variable, anopthalmia, micro-ophthalmia, hypopituitarism	Expressed in pituitary organizer, neural ectoderm and transiently in Rathke’s pouch	^{79, 231, 232}
LIM homeo
ISL1	Not known (critical role in heart development)	Rathke’s pouch induction	^{5, 233}
LHX2	Not known (regulates hematopoietic stem cells and head development)	Failure to form pituitary stalk and infundibulum. Small dysmorphic anterior lobe	²³⁴
LHX3	Hypopituitarism, variable effects on cervical spine	Pouch induction, functional overlap with LHX4	^{235, 236}
LHX4	Hypopituitarism, variable cerebellar and skull defects	Pouch induction, functional overlap with LHX3	^{49, 237}
T-box
TBX2	Dose dependent heart defects	Dispensable, but marks posterior lobe cells	^{36, 238}
TBX3	Ulnar-mammary syndrome	Required to establish Tbx2 expression, repress Shh, pituitary stalk formation, growth Rathke’s pouch	^{36, 239}
T-PIT (Tbx19)	Adrenocorticotropic hormone deficiency	Signature factor for corticotropes and melanotropes	^{67, 69, 70}
Helix-loop-helix
NEUROD1	Allelic variants cause maturity onset diabetes of the young (MODY)	Signature factor for corticotropes Delayed corticotrope development	^{66, 240-242}
NEUROD4 (Math3)	Unknown	Stimulate somatotropes expression of POU1F1, GH and GHRHR	⁵³
HES1	Chronic myelomonocytic leukemia	Notch target, regulates melanotrope cell fate	^{52, 243}
Zn finger
GATA2	Various hematopoietic defects tbx2	Suppresses gonadotrope and promotes thyrotrope fate, Pituitary KO has modest effects, Gata3 compensation	^244-246
GATA3	Hypoparathyroidism, sensorineural deafness, and renal dysplasia	Not known, overlaps with Gata2	^{245, 247}
Orphan nuclear receptor
NR5A1	Hypogonadotropic hypogonadism, Sex reversal, premature ovarian insufficiency, adrenal failure	Signature factor for gonadotropes. Activates Gnrhr, Lhb, and Fshb	^248-250
High Mobility Group
SOX2	Microophthalmia, anterior pituitary hypoplasia, hypogonadotropic hypogonadism	Anterior pituitary growth, stimulation of Pou1f1, Gh and Tshb expression, progenitor proliferation	^{251, 252}
SOX3	Hypopituitarism, mental retardation	Neural ectoderm expression (Pituitary organizer), Rathke’s pouch growth and shape	^{220, 253}
Kruppel
GLI2	Holoprosencephaly, central incisor, hypopituitarism	Regulates expression of BMP and FGF necessary for Rathke’s pouch induction	^{38, 254}
EGR1 (Krox24, Ngf1a)	Likely tumor suppressor in acute myeloid leukemia, myelodysplastic syndrome	Gh and Lhb expression	^{255, 256}
EGR2 (Krox20)	Charcot Marie Tooth disease, neuropathy	GH production	^{257, 258}

due to space constraints only selected references are listed. Additional references can be found in OMIM (http://omim.org) and MGI (http://www.informatics.jax.org)