Thymosin fraction 5 stimulates prolactin and growth hormone release from anterior pituitary cells in vitro.
Thymosin fraction 5 (TF5) is a partially purified extract of bovine thymus containing 40-60 peptides. In addition to its well documented immunopotentiating effects, TF5 reportedly modulates the secretion of some hypothalamic peptides and pituitary hormones. In this study, TF5 (10-100 micrograms/ml) stimulated PRL release from normal, MtTW15, and 7315a cells and GH release from normal and MtTW15 cells, but had no apparent effect on LH release. No changes in intracellular cAMP or cGMP levels could be correlated with these responses. Stimulation of PRL release from perifused normal anterior pituitary cells was rapid, sustained, and concentration related. Although it had no apparent effect on normal prelabeled anterior pituitary cells with respect to 45Ca2+ efflux, the calcium channel blocker D-600 inhibited TF5-mediated hormone release from these cells. Additive increases in TRH-stimulated PRL release and GRF-stimulated GH release by TF5 suggested independent mechanisms of action. Dopamine (500 nM) blocked TF5-stimulated PRL release, but somatostatin (10-100 nM) had no effect on TF5-stimulated PRL or GH release. TF5 failed to affect either basal or TRH-induced polyphosphoinositide hydrolysis. Perifused normal anterior pituitary cells prelabeled with [3H]arachidonate responded to TF5 treatment with a liberation of radioactive arachidonate and/or its metabolites. BW755c, an inhibitor of all known catabolic pathways of arachidonic acid, blocked the ability of TF5 to stimulate PRL and GH release. Reversed phase HPLC separation of TF5 into five fractions resulted in two fractions that exhibited hormone-releasing activity. These data suggest that TF5 stimulates pituitary hormone release through a mechanism different from that ascribed to TRH or GRF. The stimulus-secretion coupling mechanism involves neither polyphosphoinositide hydrolysis nor cAMP generation, but appears to be dependent on the generation of arachidonate metabolites.
Spangelo
B L
BL
Department of Internal Medicine, University of Virginia School of Medicine, Charlottesville 22908.
Judd
A M
AM
Ross
P C
PC
Login
I S
IS
Jarvis
W D
WD
Badamchian
M
M
Goldstein
A L
AL
MacLeod
R M
RM
D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D013006:Growth Hormone / Q000378:metabolism*; D007295:Inositol Phosphates / Q000378:metabolism; D007700:Kinetics; D008297:Male; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013947:Thymosin / Q000031:analogs & derivatives* / Q000494:pharmacology
D007295:Inositol Phosphates; C033782:thymosin fraction 5; D013947:Thymosin; D011388:Prolactin; D013006:Growth Hormone; D000242:Cyclic AMP