Progesterone receptor gene expression in craniopharyngiomas and evidence for biological activity

OBJECTIVE: Previous studies have demonstrated the presence of estrogen receptors in human craniopharyngiomas, raising the possibility that these lesions can be influenced by steroids. To complement these earlier findings, we examined for the presence of progesterone receptor (PR) messenger RNA in surgically removed craniopharyngiomas and performed some studies to determine whether progestogens can exert biological effects on these tumors in vitro. METHODS: Total RNA was extracted fi:om fresh surgically removed craniopharyngiomas and reverse-transcribed into cDNA. The polymerase chain reaction was applied to this craniopharyngioma-derived cDNA using amplimers complementary to exons 4 and 7 of the PR gene. Additionally, craniopharyngioma cell cultures were established, and the in vitro effects of progesterone and 6 alpha-methyl-17 alpha-hydroxyprogesterone acetate on [H-3]thymidine uptake and 17 beta-estradiol oxidoreductase activity were determined. RESULTS: Reversed-transcribed polymerase chain reaction of craniophayrngioma-derived RNA yielded bands of predicted size (389 base pairs) in six of seven tumors studied. Hinfl digestion and direct sequencing of the bands confirmed that the polymerase chain reaction DNA was representative of PR messenger RNA. Treatment of craniopharyngioma cell cultures with progesterone resulted in reduced [H-3]thymidine uptake. Both progesterone and 6 alpha-methyl-17 alpha-hydroxyprogesterone acetate powerfully increased oxidative 17 beta-estradiol oxidoreductase activity. CONCLUSION: These results provide evidence that PR messenger RNA can be produced by at least some human craniopharyngiomas and indirectly show that this is translated into biologically active receptor protein.