Eicosanoids and the Uterine Cervix
Murray D. Mitchell in Eicosanoids in Reproduction, 2020
The eicosanoids are only part of a complex web of substances that can modify the cervix structure. A web is highly organized and made of chains of events; thus, it would be inappropriate and quite meaningless to consider the eicosanoids and the cervix alone as they can be controlled by and have a controlling action on other parts of the cervix chain. In vivo investigations on the capacity of the uterine cervix to synthesize eicosanoids are confined inevitably to animals. Prostaglandin binding sites in the human cervix are enhanced by estrogen priming, but administration of progesterone following estrogen priming resulted in a down-regulation of progesterone binding sites to negligible levels. Dispersed tissue studies on the collagenous and muscle components of the cervix are required to elucidate their separate biochemical responsiveness to eicosanoids, steroids, relaxin, and oxytocin as well as their ability to synthesize the ground substances.
Eicosanoids and Blastocyst Implantation
Murray D. Mitchell in Eicosanoids in Reproduction, 2020
The involvement of eicosanoids in the decidual cell reaction is also reviewed because this reaction has been used widely and very profitably as a model for implantation. In virtually all species investigated, the earliest macroscopically observable event in blastocyst implantation is an increase in endometrial vascular permeability, which is restricted to the areas immediately adjacent to the blastocysts. The endometrium as a source of prostaglandins (PGs) regulating endometrial vascular permeability and decidualization is potentially capable of explaining the increase in permeability and subsequent decidualization brought about by both blastocysts and artificial stimuli. The localized nature of the permeability changes at implantation in most species suggests that it occurs in response to a signal from the blastocyst. Production of PGs by the blastocysts, which could then diffuse across into the endometrium, could readily explain the localized nature of the endometrial vascular permeability response.
Eicosanoid Binding Sites in Ovarian and Uterine Tissues
Murray D. Mitchell in Eicosanoids in Reproduction, 2020
The list of eicosanoid actions in ovarian and uterine tissues is incomplete and the mechanisms of action are complex and very poorly understood at best. The interaction between 5-and 15-lipoxygenases gives rise to lipoxins A and B, which have potent biological effects different from those caused by other eicosanoids. The eicosanoid structure binding-activity relationships have been summarized. The eicosanoids that bind to ovarian sites perhaps come from three major tissue sources: luteal cells, nonluteal ovarian cells, which include granulosa, theca, and stromal cells as well as nonluteal cells in corpus luteum, and the uterus. Eicosanoids have contractile and noncontractile actions in the uterus. The role of eicosanoids in the onset and progress of labor, ovum and sperm transport in the female reproductive tract, uterine blood flow, etc. is mediated by the contractile actions. Eicosanoids are also involved in endometrial changes required for blastocyst implantation.
New insights into eicosanoid biosynthetic pathways: implications for arthritis
Published in Expert Review of Clinical Immunology, 2006
Fumiaki Kojima, Mohit Kapoor, Shinichi Kawai, Leslie J Crofford
Eicosanoid is a collective term for the family of lipid mediators derived from arachidonic acid (AA) metabolism. This complex family of lipids is comprised of prostaglandins, thromboxanes, leukotrienes, hydroxyeicosatetraenoic acids (HETEs) and lipoxins (LXs). The most studied enzymatic pathway for AA metabolism proceeds via cyclooxygenase (COX). However, AA can also be metabolized by the lipoxygenases (LOXs) to LTs and HETEs, and recent studies have demonstrated a unique AA metabolic pathway mediated by both COX and LOX. Eicosanoids are also implicated as important mediators of several chronic inflammatory diseases, including rheumatoid arthritis (RA) and osteoarthritis (OA). Current therapies to treat RA and OA symptoms are directed toward the inhibition of enzymes and mediators generated within the eicosanoid pathway. This review will give insights into the current understanding of the eicosanoid biosynthetic pathway and its role in the RA and OA disease states. In addition, current therapies and future therapeutic targets within the eicosanoid pathway for the treatment of RA and OA will be discussed.
Eicosanoid Synthesis and Inactivation in Healthy and Infected Chinchilla Middle Ears
Published in Acta Oto-Laryngologica, 1997
J. Douglas Swarts, Jay Y. Westcott, Kenny H. Chan
Otitis media (OM) is an inflammatory reaction of the middle ear (ME) elicited by a variety of stimuli including tubal obstruction, allergy and bacterial infection. The leukotrienes and prostaglandins are among the earliest mediators produced in response to these insults. Their measured levels in human and animal models span a broad range of concentrations. However, their baseline levels and metabolic fates are unknown for the ME. Their dynamics in the ME were examined using the chinchilla animal model, tritiated eicosanoids and a lavage procedure. Prostaglandin levels in the normal ME were 10 times higher than the 34 pg/ear observed for the leukotrienes and thromboxane B2. These levels were significantly increased by the calcium ionophore A23187 and bacterial infection. Leukotrience C4 was the most and prostaglandin E, the least persistent eicosanoid in the ME. Their residence time in the ME was increased by infection. The rank order of eicosanoid concentrations among comparable studies was surprisingly constant, with prostaglandin E, the most abundant and the leukotrienes the least. Comparisons of eicosanoid levels from A23187 stimulation and the infectious models sampled at 3 days suggest that the higher levels observed in the infectious models may represent basal eicosanoid production for hyperplastic ME mucosa.
Polyunsaturates, endogenous eicosanoids, and cardiovascular disease.
Published in Journal of the American College of Nutrition, 1990
The role of dietary polyunsaturated fats in the prevention of human vascular disease has not been defined, but population and intervention studies have suggested that omega-3 fatty acids (FAs) from marine lipids may have a number of potentially beneficial effects. Eicosanoids are extremely potent autacoids made from polyunsaturated fatty acids and have effects on many vascular parameters, so that the physiological effects of dietary supplementation with polyunsaturated fats are often attributed to alterations in endogenous eicosanoid production. Few studies have attempted to correlate in vivo eicosanoid synthesis and functional effects during such dietary maneuvers, however. This article reviews the relationship between dietary polyunsaturates and endogenous eicosanoid synthesis in man, with particular emphasis on recent studies of the effects of omega-3 FAs. Data on omega-3 FAs and platelet-vascular interactions, blood pressure, and vascular reactivity in human subjects are also summarized, with interpretation of recent work addressing a number of controversial points. A discussion of the significance and future direction of such investigations concludes that further clinical trials in selected patient groups are warranted.