Expression of the pituitary transcription factor Ptx-1, but not that of the trans-activating factor prop-1, is reduced in human corticotroph adenomas and is associated with decreased alpha-subunit secretion.
We have studied the expression of the pituitary transcription factors Ptx-1 and Prop-1 in a series of 34 pituitary adenomas fully characterized for in vitro hormone secretion and histological staining. In studies involving mammalian cell lines, the pituitary transcription factor Ptx-1 has been shown to be a pituitary hormone panactivator, whereas more recent studies have shown that it plays an important role in alpha-subunit gene expression. Its expression has not been examined previously in human pituitary adenomas characterized by in vitro hormone secretory profiles. Of the 34 pituitary adenomas studied, Ptx-1 expression was reduced by more than 50% compared to that of the housekeeping gene human glyceraldehyde-3-phosphate dehydrogenase in the 6 corticotroph adenomas, which also had significantly reduced alpha-subunit production (all 6 tumors secreting < or =0.5 ng/24 h). Mutations of the pituitary transcription factor Prop-1, which is responsible for the syndrome of Ames dwarfism in mice, are being increasingly recognized as a cause of combined pituitary hormone deficiency in humans, although ACTH deficiency has been described only once. Prop-1 expression was detected in all 34 pituitary adenomas, including 6 corticotroph adenomas and 5 gonadotroph adenomas. The expression of Prop-1 has not been described previously in these cell phenotypes.
Skelly
R H
RH
Department of Endocrinology, St. Bartholomew's and the Royal London School of Medicine and Dentistry, London, United Kingdom. r.h.skelly@mds.qmw.ac.uk
Korbonits
M
M
Grossman
A
A
Besser
G M
GM
Monson
J P
JP
Geddes
J F
JF
Burrin
J M
JM
D000172:Acromegaly; D000236:Adenoma / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D000818:Animals; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D015292:Glycoprotein Hormones, alpha Subunit / Q000096:biosynthesis*; D018398:Homeodomain Proteins / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D051761:Paired Box Transcription Factors; D010907:Pituitary Hormones / Q000097:blood; D010911:Pituitary Neoplasms / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured
D015292:Glycoprotein Hormones, alpha Subunit; D018398:Homeodomain Proteins; D051761:Paired Box Transcription Factors; D010907:Pituitary Hormones; C102134:Prophet of Pit-1 protein; D012333:RNA, Messenger; D014157:Transcription Factors; C101485:homeobox protein PITX1; D000324:Adrenocorticotropic Hormone; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases