Effect of Lipopolysaccharide on Tumor Necrosis Factor and Prolactin Release from Rat Anterior Pituitary Cells

Abstract

TNF-alpha plays a critical role in the cascade of neuroendocrine events during inflammation and septic shock. It also affects the release of pituitary hormones and acts as a growth factor in immune and nonimmune cells. The aim of the present study was to investigate the release of TNF-alpha from rat anterior pituitary cells and the effect of the steroid medium on its release. Cultured anterior pituitary cells from lactating rats spontaneously released TNF-alpha. The presence of lipopolysaccharide (LPS, 0.1 microg/mL) in the culture medium significantly increased TNF-alpha release and inhibited prolactin release. Chronic estrogenization of ovariectomized rats or the presence of 17 beta-estradiol in the culture medium also increased TNF-alpha release. LPS significantly stimulated TNF-alpha release in all groups and abrogated the estrogen-induced prolactin release. We also investigated the effect of TNF-alpha on prolactin release. The presence of TNF-alpha (50 ng/mL) in the culture medium inhibited prolactin release from anterior pituitary cells. These data show that anterior pituitary cells in culture release TNF-alpha and that this release is stimulated by estrogens. Our results also indicate that LPS inhibits prolactin release in an estrogenic environment, suggesting that TNF-alpha could affect pituitary hormone release during endotoxemia.

Estrogens sensitize anterior pituitary gland to apoptosis

“…TNF-␣ plays a central role during endotoxemia, initiating a cascade of synthesis of other factors required for an appropriate neuroendocrine response to infection (14). TNF-␣ is expressed in the pituitary gland after LPS administration (30) and is released from anterior pituitary cells in response to LPS (25). Since the anterior pituitary gland expresses TNF-␣ receptors (31) and this cytokine induces apoptosis of anterior pituitary cells (2), circulating and/or locally produced TNF-␣ could be involved in the apoptotic response of the anterior pituitary to endotoxemia.…”

“…This sexual difference is abolished by gonadectomy and restored by administration of estradiol to ovariectomized (OVX) rats (28). We have observed that estradiol stimulates basal and LPS-induced TNF-␣ secretion from anterior pituitary cells of OVX rats (25). Also, TNF-␣ release from anterior pituitary cells varies along the estrous cycle reaching the highest levels in cells from rats at proestrus (26).…”

“…Systemic cytokines, as well as those locally released in the central nervous system and pituitary, contribute to the neuroendocrine response to endotoxemia, such as hypothalamic-pituitary-adrenal axis (HPA) activation and hypothalamic-pituitary-gonadal axis inhibition (27,28,29). We have reported that systemic LPS and central TNF-␣ administration exert inhibitory effects on prolactin secretion in male rats by stimulating dopaminergic activity in the hypothalamic-pituitary axis (4), and that LPS (25) and TNF-␣ (26) reduce in vitro prolactin release from anterior pituitary cells of female rats.…”

Nitric Oxide Mediates the Inhibitory Effect of Tumor Necrosis Factor-α on Prolactin Release

“…This cytokine is synthesized and released by anterior pituitary cells [2, 3, 4]. TNF-α binding sites have been detected in the rat anterior pituitary with a K d similar to that calculated for human and mouse TNF-α receptor (TNFR) 1 [5].…”

Intrapituitary Regulatory System of Proliferation of Mammotrophs in the Pituitary Gland

“…TNF-α induces apoptosis in somatotrophs and, in an estrogen-dependent manner, mammotrophs (Candolfi et al, 2002). It also decreases PRL release (Theas et al, 1998). TNF-α release from pituitary glands was higher during proestrus (Theas et al, 2000), thus TNF-α inhibits PRL secretion and mammotroph growth.…”