Endocrine aspects of cannabinoid action in female subprimates: search for sites of action.

The search for a site of cannabinoid action in non-primate experimental animals has raised the possibility of drug action at each level of the female reproductive system. The early suggestion that THC may have a direct "estrogen-like" action on the uterus has not been substantiated by subsequent investigations indicating that THC does not interact with the estrogen cytoplasmic receptor. Since receptor recognition is a fundamental requirement for hormone action, it is unlikely that THC acts as an estrogen. The experiments suggesting such action should be repeated under conditions where the potential confounding effects of steroids secreted from non-gonadal sources are controlled. Direct ovarian effects of THC on the ovulatory process in the rodent as well as on steroid secretion from the cells of both the corpus luteum and the preovulatory follicle have been demonstrated. Whether these effects have significance with respect to physiological function remains a question, however, in view of the rather pronounced effects of cannabinoids on the secretion of those pituitary hormones regulating these ovarian events. Only additional investigation in vivo of the more subtle gonadal effects of THC treatment can clarify this issue. With respect to the pituitary hormones, there is clear evidence for the profound effects of cannabinoid exposure, of which the most pronounced may be those on the secretion of LH and prolactin. Effects on these reproductive hormones carry the threat of potential disturbance of the reproductive process, especially in the female where there is great dependence upon the appropriate cyclic changes in hormone levels. The full biologic impact of the pituitary effects of cannabinoids requires careful and thorough assessment. It can be concluded with reasonable confidence that THC alters the secretion of the pituitary reproductive hormones, and that of ACTH as well, through actions in the brain. While it would be reasonable to suggest that this site of action may reside in the MBH, the region of the hypothalamus most intimately associated with pituitary function, that does not seem to be the case for effects on prolactin and ACTH. Prevention of the expression of THC effects on these hormones by MBH deafferentation points to a more distant site for THC action. Some of the more likely possible sites for THC inhibition of prolactin secretion have been investigated, but direct evidence for their involvement was not forthcoming.(ABSTRACT TRUNCATED AT 400 WORDS)