**Section 2**

**Pathogenesis** 

112 Endometriosis - Basic Concepts and Current Research Trends

Knapp VJ (1999). How old is endometriosis? Late 17th- and 18th-century European

Lauchlan SC (1972). The secondary Mullerian system. *Obstet Gynecol Surv* 27(3):133-46 Lauchlan SC (1994). The secondary Mullerian system revisited. *Int J Gynecol Pathol* 13(1):73-9 Sasson IE,Taylor HS (2008). Stem cells and the pathogenesis of endometriosis. Ann. NY

descriptions of the disease. *Fertil Steril* Jul;72(1):10-4.

Acad. Sci. 1127:106-115

**7** 

*Argentina* 

**Involvement of Prostaglandins in the** 

*Instituto de Biología y Medicina Experimental (IBYME-CONICET) Buenos Aires,* 

Prostaglandins (PGs), thromboxanes (TXs) and leukotrienes (LTs) collectively called eicosanoids, are cyclooxygenase (COX) and lipoxygenase (LOX) products. Prostanoids, PGs and TXs, are known effectors of a wide range of actions in most cells and tissues. They have been described to be involved in muscle contraction and relaxation, neurotransmitter release/unrelease, fever, sleep induction, apoptosis, cell proliferation and oncogenesis; but respecting endometriosis, what matters us mostly, is that they are central molecules

Arachidonic acid (AA) is the precursor of all eicosanoids. Phospholipase A2 splits AA from plasma membrane phospholipids; once free in the cytosol it is cyclized, oxygenated and reduced to the intermediary PGH2 by the COX enzymes; or to hydroperoxyeicosatetraenoic

Two *COX* genes are known to be highly conserved throughout the species. *COX-1* gene has several splice variants: the most widely known COX-1 enzyme, the less known counterparts COX-3 and other smaller variants of the COX-1 (Chandrasekharan et al., 2002; Chandrasekharan & Simmons, 2004). *COX-2* gene has, up to now, only one known protein. COX-1 is ubiquitously and constitutively expressed. It was long thought of COX-1 as the enzyme that was involved only in physiological conditions, but was proven to be upregulated in various carcinomas and to be involved in tumorigenesis (Hwang et al., 1998; Kitamura et al., 2002; Sales et al., 2002). COX-2 enzyme is physiologically induced by growth factors and cytokines; it functions when the concentrations of AA are very low (Fortier et al., 2008). Furthermore COX-2 was seen to be overexpressed in several pathological circumstances as different types of cancers, where its high expression correlates with a negative prognosis, and other inflammation related diseases, as endometriosis (Matsuzaki et

PGH2 synthesized by the COXs, is used as a substrate to produce the terminal prostanoids by the PG synthases; each of them is named by their product: PGD2, PGE2, PGF2α, prostacyclin (PGI2) and thromboxane (TX) A2 are produced by PGD synthase (PGDS), PGE

involved in the reproductive system (Jabbour & Sales, 2004; Narumiya et al., 1999).

acid (HPETE) by LOX enzymes, when the LT pathway is followed.

**1. Introduction** 

al., 2004; Ota et al., 2001).

**1.1 Prostaglandin synthesis and function** 

**Pathophysiology of Endometriosis** 

Gabriela F. Meresman and Carla N. Olivares
