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

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 beta-endorphin (i beta-E) by mouse corticotropic tumor cells. The release of i beta-E by AtT-20 pituitary tumor cells was increased in a dose-dependent manner by concentrations of 30-600 micrograms/ml of TSN-5, whereas concentrations greater than 1,000 micrograms/ml were increasingly less effective in stimulating secretion. TSN-5 (600 micrograms/ml) significantly stimulated i beta-E release within 7 min; maximal secretory responses (up to 275% of control release) occurred by 4 hr. The secretory response of AtT-20 cells to 600 micrograms/ml TSN-5 (37.9 +/- 2.0 vs. 16.1 +/- 1.0 ng i beta-E/ml/4 hr, mean +/- SE) was similar in magnitude to release evoked by 0.1 microM corticotropin-releasing factor (CRF). Combining TSN-5 and CRF treatments increased secretion of i beta-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 i beta-E in AtT-20 cell extracts after 24-hr treatment by 45% (231.8 +/- 24.7 vs. 417.2 +/- 17.8 ng i beta-E/mg protein, CRF vs. vehicle treatments, respectively), TSN-5 did not significantly alter cellular hormone content. Neither TSN-alpha 1 nor TSN-beta 4, two of the component peptides of TSN-5, affected basal or CRF-stimulated release of i beta-E, indicating that an unidentified constituent(s) is corticotropic.(ABSTRACT TRUNCATED AT 250 WORDS)