Thymosin fraction 5 stimulates secretion of immunoreactive ?-endorphin in mouse corticotropic tumor cells

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Abstract
In addition to reconstituting immune competence, the thymus gland preparation, thymosin fraction 5 (TSN-5), has recently been shown to stimulate secretion of hormones from the hypothalamic-pituitary adrenal axis in vivo and from pituitary corticotropes in vitro. The purpose of the present study was to investigate the effects of TSN-5 on secretion of immunoreactive β-endorphin (iβ-E) by mouse corticotropic tumor cells. The release of iβ-E by AtP-20 pituitary tumor cells was increased in a dose-dependent manner by concentrations trations of 30–600 pg/ml of TSN-5, whereas concenconcentrations greater than 1,000 μg/ml were increasingly less effective in stimulating secretion. TSN-5 (600 μg/ml) significantly stimulated iβ-E release within 7 min; maximal secretory responses (up to 275% of control release) occurred by 4 hr. The secretory response of AtP-20 cells to 600 μg/ml TSN-5 (37.9 ± 2.0 vs. 16.1 ± 1.0 ng iβ-E/ml/4 hr, mean ± SE) was similar in magnitude to release evoked by 0.1 μM corticotropin-releasing factor (CRF). Combining TSN-5 and CRF treatment increased secretion of iβ-E to nearly 600% of control levels, an effect greater than an additive influence of the two independent treatments. Whereas CRF treatment reduced the levels of iβ-E in AtP-20 cell extracts after 24-hr treatment by 45% (231.8 ± 24.7 vs. 417.2 ± 17.8 ng iβ-E/mg protein, CRF vs. vehicle treatments, respectively), TSN-5 did not significantly alter cellular hormone content. Neither TSN-α1 nor TSN-β4, two of the component peptides of TSN-5, affected basal or CRF-stimulated releast of iβ-E, indicating that an unidentified constituent(s) is corticotropic. This study demonstrates that TSN-5 directly stimulates hormone release from AtT-20 cells and potentiates the secretory actions of CRF. These findings support the concept of interactions between neuroendocrine and immune regulators of the hypothalamic-pituitary adrenal axis. Additionally, corticotropic tumor cells appear to be a useful model in which to differentiate a hormonally active constitutent(s) of TSN-5 and evaluate the cellular mechanisms of action of TSN-5 on corticotropic cells.