Functional role of estrogen in pituitary tumor pathogenesis

Pituitary hyperplasia and lactotroph replication are induced by estrogen. The product of the pituitary tumor transforming gene (PTTG) exhibits in vitro and in vivo transforming activity and induces basic bFGF secretion, thereby modulating pituitary angiogenesis and tumor formation. We demonstrated p...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of clinical investigation 2002, Vol.109 (2), p.277-283
Main Authors: Heaney, Anthony P, Fernando, Manory, Melmed, Shlomo
Format: Article
Language:English
Subjects:
Adenoma - etiology
Adenoma - metabolism
Animals
Estradiol - analogs & derivatives
Estradiol - pharmacology
Estrogen Antagonists - pharmacology
Estrogens - immunology
Estrogens - physiology
Female
Gene Expression Regulation
Humans
Neoplasm Proteins - genetics
Pituitary Neoplasms - etiology
Pituitary Neoplasms - metabolism
pituitary tumor-transforming gene
Rats
Rats, Inbred F344
Rats, Inbred WF
Rats, Long-Evans
Securin
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Pituitary hyperplasia and lactotroph replication are induced by estrogen. The product of the pituitary tumor transforming gene (PTTG) exhibits in vitro and in vivo transforming activity and induces basic bFGF secretion, thereby modulating pituitary angiogenesis and tumor formation. We demonstrated previously that pituitary pttg is induced by estrogen and bFGF, the latter being expressed in a concordant fashion with pttg in experimental and human pituitary adenomas. We now elucidate the role of estrogen in paracrine regulation of pituitary tumorigenesis by PTTG. Coincident with the circulating rat estradiol surge and maximal pituitary proliferation, pituitary pttg mRNA, bFGF, and VEGF expression increased approximately threefold during proestrus and estrus. Osmotic mini-pump coinfusion of estrogen and antiestrogen abrogated estrogen-induced pituitary pttg expression in vivo, suppressed serum PRL concentrations by 88%, and attenuated prolactin-secreting pituitary tumor growth by 41% in rats. Antiestrogen treatment of primary human pituitary tumor cultures reduced PTTG expression approximately 65%. Pituitary pttg, bFGF, and VEGF are cyclically expressed during the rat estrus cycle, concordantly with estrogen levels. Because anti-estrogens reduced PTTG expression in human pituitary tumors in vitro and suppressed experimental tumor growth in vivo, concomitantly with reduced PRL secretion, these results indicate a role for selective antiestrogens in treating pituitary tumors.
ISSN:0021-9738
DOI:10.1172/jci0214264