Estrogens modulate the inhibitory effect of tumor necrosis factor-alpha onanterior pituitary cell proliferation and prolactin release

Considering that tumor necrosis factor-alpha (TNF-alpha) is involved in nor mal tissue homeostasis and that its receptors are expressed in the anterior pituitary, we examined the effect of this cytokine on pituitary cell growt h. Because anterior pituitary function depends on hormonal environment, we also investigated the influence of gonadal steroids in the effects of TNF-a lpha on cell proliferation and the release of PRL from anterior pituitary c ells. In addition, the release of TNF-alpha and its action on the release o f PRL from anterior pituitary cells of rats at different stages of the estr ous cycle was evaluated. In minimum essential medium io-valine, a medium th at restricts fibroblastic proliferation, TNF-alpha (10 and 50 ng/mL) reduce d H-3-Thymidine incorporation, DNA content, and active cell number. TNF-alp ha failed to affect proliferation of cells from ovariectomized (OVX) rats. However, it significantly inhibited growth of cells from OVX rats cultured with 17 beta-estradiol (E-2) (10(-9) M) and from chronically estrogenized r ats, TNF-alpha decreased the release of PRL from cells of intact rats, espe cially in proestrous, OVX rats cultured with E-2 and chronically estrogeniz ed rats. The release of anterior pituitary TNF-alpha was higher in proestro us rats. These results indicate that TNF-alpha plays an inhibitory role in anterior pituitary cell growth and the release of PRL in an estrogen-depend ent manner.