Biology of Reproduction, Vol 24, 315-322, Copyright © 1981 by Society for the Study of Reproduction

Effects of Cannabinoids and Female Exposure on the Pituitary-Testicular Axis in Mice: Possible Involvement of Prostaglandins

¹ Departments of Pharmacology, Anatomy, and Obstetrics and Gynecology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas 78284

In immature (30-35-day-old) mice, a single dose of ⁹-tetrahydrocannabinol (THC), the main psychoactive constituent of marihuana, decreased plasma testosterone (T), LH, and FSH levels, but the same dose of a nonpsychoactive component, cannabinol (CBN), had no effect. Chronic exposure to THC, CBN, or cannabidiol (CBD), beginning at 30 days of age through adulthood, influenced the endocrine responses to a sexually receptive female. Thus, weights of testes and seminal vesicles were reduced in males from all cannabinoid-treated groups on the day after exposure to a female, compared with treated males housed in all-male groups. Plasma FSH concentrations were elevated in CBN-exposed mice, regardless of social experience, while plasma T levels were increased after an encounter with a female in all but THC-treated males. Plasma LH levels and testicular responsiveness to gonadotropins in vitro were reduced in THC-and CBN-treated mice exposed to a female. In contrast, in THC- or CBN-treated males maintained in all-male groups, T production in vitro was significantly elevated. Alterations in prostaglandin (PG) concentrations may mediate these effects of cannabinoids and sexual encounter since production of PG in vitro by testis and pituitary was reduced by exposing cannabinoid-treated males to female-related stimuli. In contrast, sexual encounter increased PCF, but had no effect on PGE production by pituitary or testes obtained from oil-treated controls. Both psychoactive and nonpsychoactive constitutents of marihuana are capable of altering the function of the pituitary-gonadal axis and of influencing the endocrine responsivity to female-related exteroceptive cues in male mice.

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ACKNOWLEDGMENTS We would like to thank M. P. Hogan and Dr. H. Klemcke for their assistance, W. Friedrichs for prostaglandin incubations and RIA, and Dr. J. Pike, Upjohn Co., for the gift of unlabeled prostaglandins. We would also like to thank R. Hogg and Ayerst Co. for the generous supply of LRF. We acknowledge the support of the Radioimmunoassay Core Laboratory [grant P 30 HD 10202 and NIDA grant 1 RO1 DA 02342-01 (A.B.)]. We also thank C. Small for her excellent preparation of this manuscript.