Bacterial lipopolysaccharide (LPS) induces apoptosis in the anterior pituitary gland from female rats in an estrogen-dependent manner

J. FERRARIS; S. NAVARRA; M. CANDOLFI; V. ZALDIVAR; A. SEILICOVICH; D. PISERA

Philadelphia, USA

Congreso; 85o Annual Meeting of the Endocrine Society; 2003

Bacterial lipopolysaccharide (LPS) induces apoptosis in the anterior pituitary gland from female rats in an estrogen-dependent manner   Death by apoptosis is known to have a major role in the maintenance of tissue homeostasis. Apoptosis occurs both in normal and tumoral anterior pituitary cells. We have previously shown that TNF-á induces apoptosis in somatotropes and lactotropes from female rats (1). The apoptotic effect of TNF-á on lactotropes is dependent on estrogens. Since LPS stimulates cytokine release, we studied whether LPS induces apoptosis (by TUNEL method) in the anterior pituitary of ovariectomized (OVX) rats, chronically estrogenized (by implanting sylastic capsules containing 1 mg 17-b estradiol, E2), or cycling rats.   The chronic treatment with E2 increased the number of TUNEL positive cells/field in anterior pituitary slices. The  i.p. administration of LPS (250 ug/rat, 8h) increased the apoptotic index only in chronically estrogenized rats (OVX:. 0.31 ± 0.07; OVX+E2: 2.19 ± 0.22, p< 0.05; OVX+LPS: 0.34 ± 0.11; OVX+E2 +LPS: 18.58 ± 1.10; p<0.001, two-way ANOVA). Approximately 75% of apoptotic cells were identified as lactotropes by immunocytochemistry using prolactin antiserum. No apoptotic somatotropes were observed.   The number of TUNEL positive cells was significantly increased 6 h after the administration of LPS to rats at proestrus (P: 0.86 ± 0.25; P+LPS: 16.45 ± 1.38, p< 0.001) and diestrus (D: 0.60 ± 0.19; D+LPS: 4.50 ± 0.61, p< 0.001) but the effect of LPS was significantly higher in proestrus than in diestrus (p<0.001, two-way ANOVA) These results indicate that estrogens have an apoptotic effect in the anterior pituitary and allow the induction of apoptosis by LPS. Gonadal steroids may modulate the apoptotic response to endotoxemia in the pituitary during the estrous cycle.   (1) Candolfi M, Endocrinology  143:3611-3617, 2002