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Production of interleukin-6 by anterior pituitary cells in vitro
B L Spangelo1, R M MacLeod, P C Isakson
1Department of Medicine, University of Virginia Health Sciences Center, Charlottesville 22908.
Insights
The anterior pituitary gland produces the cytokine interleukin-6 (IL-6) in situ, suggesting it acts locally to regulate hormone release. This finding reveals a novel intrapituitary mechanism for hormone secretion.
Area of Science:
- Endocrinology
- Cell Biology
- Neuroscience
Background:
- Interleukin-6 (IL-6) is known to stimulate anterior pituitary hormone release in vitro.
- IL-6 is typically not detectable in systemic circulation, prompting investigation into local production.
Purpose of the Study:
- To investigate the hypothesis that the anterior pituitary produces IL-6 in situ.
- To determine if locally produced IL-6 influences pituitary hormone secretion via paracrine or autocrine signaling.
Main Methods:
- Culturing anterior pituitary cells and measuring IL-6 secretion in the incubation medium.
- Stimulating IL-6 production using phorbol myristate acetate and lipopolysaccharide.
- Assessing IL-6 secretion from freshly dissected hemipituitary tissue.
Main Results:
- Cultured anterior pituitary cells spontaneously secreted significant amounts of IL-6 (2000-4000 U/ml within 8 hours).
- IL-6 production was dose-dependently stimulated by phorbol myristate acetate and lipopolysaccharide.
- Fresh hemipituitary tissue also secreted substantial IL-6, further enhanced by lipopolysaccharide.
Conclusions:
- The anterior pituitary gland produces IL-6 in situ.
- Locally produced IL-6 may function as an intrapituitary releasing factor, regulating hormone secretion within the gland.
Abstract:
We recently reported that the cytokine interleukin-6 (IL-6) is a potent stimulator of anterior pituitary hormone release in vitro. Since IL-6 is not normally detectable in the blood, we hypothesized that IL-6 may be produced by the anterior pituitary in situ and thereby affect hormone secretion through paracrine or autocrine mechanisms. The present study demonstrates that cultured anterior pituitary cells spontaneously secrete large quantities of IL-6 in vitro. IL-6 was detectable in the incubation medium within 2 h, and by 8 h of culture had attained concentrations of 2000-4000 U/ml.4 x 10(5) cells. IL-6 production was stimulated by phorbol myristate acetate (10-100 nM) approximately 2-fold and by lipopolysaccharide (0.001-10.0 micrograms/ml) 4-fold during 4-h incubations. In contrast, the cytokine recombinant human IL-1 alpha had no effect on IL-6 release by cultured pituitary cells. Freshly dissected hemipituitary tissue also secreted more than 3000 U/ml IL-6 during a 4-h incubation. This secretion was enhanced 3-fold by 10 micrograms/ml lipopolysaccharide. Our results suggest that the anterior pituitary may produce IL-6 in situ, where it may function as an intrapituitary releasing factor.
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