delta9-Tetrahydrocannabinol and 17beta-estradiol bind to different macromolecules in estrogen target tissues.

delta9-Tetrahydrocannabinol (delta9-THC), added to the limit of its solubility, did not compete with tritiated 17beta-estradiol for binding to estrogen receptor sites in mouse mammary or uterine cytosols. On sucrose density gradients of low-ionic strength, mammary cytosol labeled with [3H]estradiol exhibited a binding peak near the "8S" region typical of estrogen receptor whereas in cytosol labeled with delta9-[3H]THC binding was limited to the nonspecific 4- to 5S region. Differences in sedimentation properties and reciprocal competition studies strongly refute previous claims that delta-9-THC binds to estrogen receptor and that by so doing it directly acts as an estrogen.