EFFECTS OF 9-ENE-TETRAHYDROCANNABINOL ON EXPRESSION OF BETA-TYPE TRANSFORMING GROWTH-FACTORS, INSULIN-LIKE GROWTH FACTOR-I AND C-MYC GENES IN THE MOUSE UTERUS

Effects of cannabinoid on expression of beta-type transforming growth factors (TGF-beta1,-beta2 and -beta3), insulin-like growth factor-I (I GF-I) and c-myc genes in the uteri of adult ovariectomized mice were e xamined using Northern blot hybridization. Mice were exposed to 9-ene- tetrahydrocannabinol (THC) alone or in combination with an injection o f estradiol-17beta (E2) and/or progesterone (P4), and uteri were analy zed at various times thereafter. TGF-beta isoform messenger RNAs (mRNA s) persisted in ovariectomized uteri and their levels were not altered after THC treatment, whereas an injection of E2 caused a modest incre ase in TGF-beta1 and -beta3 mRNA levels at 24 h. Imposition of THC tre atment advanced the stimulatory effects of E2 by changing the timing f or the peak of TGF-beta3 mRNA levels to 12 h. In comparison, E2 treatm ent substantially elevated the levels of TGF-beta2 mRNA at 6 h, and TH C potentiated this E2 response without affecting the timing for the re sponse. Imposition of P4 treatment did not antagonize any of these res ponses. P4 treatment alone or with THC had insignificant effects on mR NA levels for these TGF-beta isoforms. Uterine levels of IGF-I and c-m yc mRNAs were low in ovariectomized mice and THC did not alter these m RNA levels. In contrast, E2 treatment induced a rapid, but transient, increase in IGF-I and c-myc mRNAs, and THC antagonized the rapid c-myc mRNA response and altered the timing of the IGF-I mRNA response. P4 t reatment alone also caused the transient induction of these mRNAs, but THC failed to antagonize these effects. An injection of P4 plus E2 re sulted in further modest increases in IGF-I and c-myc mRNA levels as c ompared to E2 Or P4 treatment alone. However, THC did not antagonize t hese transient stimulatory effects of the combined ovarian steroids. T he data suggest that THC should not be classified as estrogenic or ant iestrogenic. However, this compound can modulate (potentiate, antagoni ze and/or alter timing) the effects of ovarian steroids on uterine gen e expression.