Functional role of estrogen in pituitary tumor pathogenesis

treatment blocks estrogen-induced pituitary pttg expression in vitro and in vivo and inhibits lactotroph tumor growth in vivo.Estrogen-regulated PTTG, bFGF, and VEGF expression may therefore play a role in the early molecular events leading to development of pituitary transformation and prolactinoma development. Methods Animals.Ovariectomized Fischer 344 rats (140-150 g; Harlan Sprague Dawley Inc., Indianapolis, Indiana, USA) were housed in a controlled environment (light on, 0500-1900 hours, 24°C) with free access to food and water, and their use was approved by the Institutional Animal Care and Use Committee.Subcutaneously implanted osmotic pumps (OP) (100 µl, ALZET), containing 17-β-estradiol (1,000 ng), 4-hydroxytamoxifen (860 µg), ICI-182780 (500 µg), or raloxifene (480 µg) in 90% polyethylene glycol (PEG)/5% ethanol/5% DMSO solution were employed to infuse estrogen and/or antiestrogen for 48-hour intervals.For study of pttg expression during the rat estrus cycle, daily vaginal smears were collected from twenty, 4-day cycling, virgin female Long-Evans rats (12 weeks of age), housed as above, to determine their estrus cycle patterns.Only animals that exhibited at least three consecutive 4day cycles were considered to be regularly cyclic and used in subsequent experiments.Rats were euthanized in the early afternoon (1400 hours) by CO 2 inhalation, pituitary tissues immersed in liquid N 2 and stored at -80°C