Effects of 9-ene-tetrahydrocannabinol on expression of β-type transforming growth factors, insulin-like growth factor-I and c- myc genes in the mouse uterus

Abstract

Effects of cannabinoid on expression of β-type transforming growth factors (TGF-β1, -β2 and -β3), insulin-like growth factor-I (IGF-I) and c- myc genes in the uteri of adult ovariectomized mice were examined using Northern blot hybridization. Mice were exposed to 9-ene-tetrahydrocannabinol (THC) alone or in combination with an injection of estradiol-17β (E 2) and/or progesterone (P 4), and uteri were analyzed at various times thereafter. TGF-β isoform messenger RNAs (mRNAs) persisted in ovariectomized uteri and their levels were not altered after THC treatment, whereas an injection of E 2 caused a modest increase in TGF-β1 and -β3 mRNA levels at 24 h. Imposition of THC treatment advanced the stimulatory effects of E 2 by changing the timing for the peak of TGF-β3 mRNA levels to 12 h. In comparison, E 2 treatment substantially elevated the levels of TGF-β2 mRNA at 6 h, and THC potentiated this E 2 response without affecting the timing for the response. Imposition of P 4 treatment did not antagonize any of these responses. P 4 treatment alone or with THC had insignificant effects on mRNA levels for these TGF-β isoforms. Uterine levels of IGF-I and c- myc mRNAs were low in ovariectomized mice and THC did not alter these mRNA levels. In contrast, E 2 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. P 4 treatment alone also caused the transient induction of these mRNAs, but THC failed to antagonize these effects. An injection of P 4 plus E 2 resulted in further modest increases in IGF-I and c- myc mRNA levels as compared to E 2 or P 4 treatment alone. However, THC did not antagonize these transient stimulatory effects of the combined ovarian steroids. The data suggest that THC should not be classified as estrogenic or antiestrogenic. However, this compound can modulate (potentiate, antagonize and/or alter timing) the effects of ovarian steroids on uterine gene expression.