Prolonged effects of tumor necrosis factor-alpha on anterior pituitary hormone release

We examined the chronic (72 h) effects of 30 ng/ml recombinant murine tumor necrosis factor (TNF)-alpha on release of immunoreactive growth hormone (GH), prolactin (PRL), thyrotropin (TSH), and TSH glycosylation, as assessed by lectin binding, in cultured rat anterior pituitary cells. In cultured cells from adult female rats, TNF-alpha significantly suppressed basal and GH-releasing hormone (GRH)-stimulated GH release. TNF-alpha also suppressed basal PRL release and completely abolished the PRL response to TRH (0.1-10 nM). Whereas TNF-alpha reduced basal TSH release, it significantly enhanced the maximal TSH response to TRH. TNF-alpha did not affect the concanavalin A and lentil lectin binding of TSH accumulated in the medium during the 4-day culture, but significantly decreased the lentil lectin binding of TSH released in response to acute TRH stimulation. TNF-alpha significantly enhanced the inhibitory effect of somatostatin on stimulated PRL release, but not on GH or TSH release. Compared to cell cultures from adult female rats, in anterior pituitary cell cultures from 12-day-old rats the effects of prolonged exposure to TNF-alpha on hormone release were diminished or absent. Pituitary hormone release was unaffected by acute (3 h) exposure to TNF-alpha. These results demonstrate a direct effect of TNF-alpha on anterior pituitary hormone release, which is cell-type specific and age dependent.