Constitutive Expression of Prostaglandin-Endoperoxide Synthase 2 by Somatic and Spermatogenic Cells Is Responsible for Prostaglandin E2 Production in the Adult Rat Testis1

Abstract

Prostaglandins (PGs), particularly PGE(2), have been implicated in the control of testicular steroidogenesis, spermatogenesis, and local immunity. However, virtually nothing is known about the expression or activity of the prostaglandin-endoperoxide synthases (PTGSs; also referred to as the cyclooxygenases), the specific rate-limiting enzymes responsible for PG production, in the adult testis. This activity was investigated in rats under normal conditions and during lipopolysaccharide-induced inflammation using quantitative real-time PCR, in situ hybridization, Western blotting, and PGE(2) measurements by ELISA. The mRNA for both the "constitutive" Ptgs1 and the "inducible" Ptgs2 forms was detected in multiple testicular cell types. Testicular Ptgs2 expression was substantially higher than that of Ptgs1, and testicular production of PGE(2) in vitro was found to be suppressed by a specific PTGS2 inhibitor (NS-398), but not by an inhibitor of PTGS1. Further investigation indicated that 1) PGE(2) production in the adult testis is attributable to constitutive expression of PTGS2 by somatic (Leydig cells and Sertoli cells) and spermatogenic cells; 2) testicular macrophages constitutively produce relatively low levels of PTGS2 and PGE(2) but are the only cell type to respond significantly to an inflammatory stimulus by increasing production of PGE(2); and 3) testicular PTGS2 expression and intratesticular PGE(2) levels are only marginally affected by acute inflammation. These data point toward a previously unanticipated maintenance role for the "inducible" PTGS2 enzyme in normal testicular function, as well as an anomalous response of testicular PTGS2 to inflammatory stimuli. Both observations are consistent with the reduced capacity of the testis to initiate and support inflammatory reactions.

Characterization of the Micro-Environment of the Testis that Shapes the Phenotype and Function of Testicular Macrophages

“…However, the IF is known to contain nonproteinaceous factors such as the T cell inhibitor, lyso-glycerophosphocholine, and PG (37). In the testis, PG are mainly produced by SC, LC, PTC, and TM (38)(39)(40). PG have also been implicated in polarizing macrophage phenotypes by inhibiting the production of TNF-a and upregulating the production of IL-10 via cAMP-CREB (41,42).…”

Regulation of Smooth Muscle Contraction by the Epithelium: Role of Prostaglandins

“…Interestingly, the PG production in rats was also found to be sensitive to FSH, the gonadotropin controlling spermatogenesis, indicating the involvement of Sertoli cellderived PGs in sperm production in the testis (35,82). The expression of COX2 in the testis has been found in Leydig cells, Sertoli cells, and spermmatogenic cells of the rat (80,198), but only in Leydig cells of the hamster (57). The exact roles of PGs from different cell types, particularly those from Sertoli cells, in spermatogenesis remain largely unknown.…”

Vascular endothelial growth factor regulates germ cell survival during establishment of spermatogenesis in the bovine testis

“…2E). Prostaglandin-endoperoxide synthase 2 (PTGS2) is critical for germ cell maturation and somatic-germ cell interactions in the mammalian gonad both in vivo and in vitro (Neal et al 1975, Takahashi et al 2006, Winnall et al 2007. Recent evidence suggests that this multifunctional enzyme is also responsible for protecting mouse embryonic stem cells and renal interstitial cells from oxidative stress and hypertonicity-induced apoptosis (Moeckel et al 2003, Liou et al 2007); thus, we evaluated the mRNA expression of PTGS2 in response to VEGF treatment.…”