delta 9-Tetrahydrocannabinol antagonism of the anterior pituitary response to estradiol in immature female rats.
The potential estrogenicity or antiestrogenicity of delta 9-tetrahydrocannabinol (THC), the chief psychoactive constituent of marijuana, was evaluated in immature female rats treated for 3 days with estradiol (E2; 1 microgram/kg), THC (10 mg/kg body weight), or E2 + THC. Estradiol treatment significantly increased anterior pituitary, uterine, and oviduct weights. When THC was administered with E2, it prevented the E2-induced increase in pituitary weight, but had no effect on either the uterine or oviduct weight response to E2. In the E2 treatment group, basal prolactin levels were increased and a prolactin surge occurred on the afternoon of the 26th day of age. However, E2-stimulated basal and surge levels of prolactin were significantly attenuated by concomitant THC treatment. Moreover, pituitary prolactin concentrations, which were elevated in E2-treated rats, did not differ from control values in E2 + THC-treated animals. The E2-induced decrease in dopamine turnover rates in the medial basal hypothalamus and increase in the number of anterior pituitary dopamine D2-binding sites (Bmax) were not affected by concomitant THC treatment. Thus, THC antagonizes E2 action on the anterior pituitary via yet to be elucidated mechanism(s).
Murphy
L L
LL
Department of Physiology, Southern Illinois University School of Medicine, Carbondale 62901-6512.
Rodriguez de Fonseca
F
F
Steger
R W
RW
D000818:Animals; D004298:Dopamine / Q000378:metabolism; D013759:Dronabinol / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005187:Fallopian Tubes / Q000033:anatomy & histology; D005260:Female; D007033:Hypothalamus, Middle / Q000187:drug effects / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010903:Pituitary Gland, Anterior / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*; D011388:Prolactin / Q000097:blood / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000378:metabolism; D017448:Receptors, Dopamine D2; D014599:Uterus / Q000033:anatomy & histology
D004965:Estrogen Antagonists; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D004958:Estradiol; D013759:Dronabinol; D011388:Prolactin; D004298:Dopamine