Tumor Necrosis Factor-alpha induces apoptosis of lactotropes from female rats

Abstract

TNF-α is involved in the regulation of normal tissue homeostasis affecting cell proliferation, differentiation, and death. We previously reported that TNF-α reduces anterior pituitary cell proliferation and PRL release in an estrogen-dependent manner. In the present project we studied the induction of apoptosis by TNF-α in anterior pituitary cells from female rats. TNF-α (50 ng/ml) decreased the viability of anterior pituitary cells. Incubation with TNF-α for 24 h increased the percentage of terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate nick end labeling-positive cells. TNF-α increased the percentage of somatotropes and lactotropes with apoptotic nuclear morphology without affecting the proportion of apoptotic corticotropes or gonadotropes. TNF-α increased the percentage of apoptotic lactotropes in cultured cells from rats killed in proestrus and estrus, but not in diestrus. This effect was significantly higher in cells from rats in proestrus than in estrus. In anterior pituitary cells from ovariectomized rats, TNF-α significantly increased the percentage of apoptotic lactotropes only when the cells were incubated in the presence of 17β-estradiol. These results indicate that TNF-α induces apoptosis in somatotropes and lactotropes from female rats. The apoptotic effect of TNF-α on lactotropes is dependent on estrogens and could be involved in the regulation of anterior pituitary cell renewal during the estrous cycle.