In previous studies
GnRH-III, a variant of the hypothalamic
neurohormone GnRH, was isolated from the brain of the sea lamprey and structurally characterized.
GnRH-III is a hypothalamic
neurohormone in both female and male sea lampreys. In the present work
biological activities of
GnRH-III in mammalian systems were examined. In superfused rat pituitary cells,
GnRH-III at 1 nM to 100 nM neither induced LH-secretion nor inhibited the LH-secretion elicited by native
GnRH and elicited LH release only at 1 microM. At high dose (500 microg/day) in vivo,
GnRH-III behaved as a
GnRH agonist, though, it was 1000-fold less active than
ovurelin. The in vitro and in vivo results were in good agreement in showing that
GnRH-III is only a weak agonist of the endocrine activity of
GnRH.
GnRH-III specifically bound to receptors on
cancer cells and recognized not only the high-, but also the low-affinity binding sites.
GnRH-III significantly suppressed growth of human
cancer cells which have
GnRH receptors. The inhibitory effect of
GnRH-III on growth of
cancer cells was specific and direct since the
peptide did not have endocrine activity in the concentration range found to be effective in anticancer assays.
GnRH-III inhibited equally the growth of ER-positive and -negative breast and TeR-positive and negative prostate cells.