Significance of prostaglandins in the regulation of cyclic events in the ovary and uterus.

We examined the role of prostaglandins in three pivotal events of the female reproductive cycle: ovulation, luteolysis, and menstruation. Four general approaches were adopted, using in vivo and in vitro models: use of inhibitors of cyclooxygenase and of PG action; immunoneutralization of individual prostaglandins; administration of exogenous prostaglandins; and attempts to correlate PG levels in tissues and body fluids to physiologic events. It can be concluded that prostaglandins or related metabolites of arachidonic acid are essential in laboratory rodents for follicular rupture and the release of a fertilizable oocyte, but not for other LH actions on the follicle that are mimicked by PG or for the neuroendocrine triggering of ovulation. PGs control the cyclic regression of the corpus luteum and appear also to be implicated in the decidual reaction and in the menstrual shedding of the endometrium in primates. Some aspects of the control of follicular PG formation and of PG action were analyzed. Gonadotropins stimulate follicular PG synthesis by a steroid-independent cyclic nucleotide-mediated induction of cyclooxygenase. Both the thecal and granulosa cell compartments show this response. An effect of the phytolectin conconalavin A on ovarian PG synthesis is described. The response of follicular cells to prostaglandin E2 exhibits the phenomenon of desensitization and is influenced by agents modifying the structure and function of cytoskeletal elements. Evidence is put forward for the view that abrogation by PGF2 alpha of the stimulatory action of LH on luteal adenylate cyclase is the biochemical basis of the luteolytic action of this prostaglandin. While the precise mechanism of PG action on the endometrium remains to be defined, PG-synthetase inhibitors have already found useful applications in the management of menstrual disorders, such as functional dysmenorrhea and menorrhagia. The role in ovarian and uterine physiology of the more recently discovered labile arachidonate metabolites, such as the endoperoxides, prostacyclin, and thromboxanes, has not yet been adequately explored.