The role of glucocorticoid in the regulation of prostaglandin biosynthesis in non-pregnant bovine endometrium

Abstract

To determine whether glucocorticoids (GCs) play a role in regulating uterine function in cow, the present study examined the expression of mRNA encoding GC receptor (GC-R) a, 11b-hydroxysteroid dehydrogenase (11-HSD) type 1 and type 2, and the activity of 11-HSD1 in bovine endometrial tissue throughout the estrous cycle. We also studied the effects of cortisol on basal, oxytocin (OT)-and tumor necrosis factor-a (TNFa)-stimulated prostaglandin (PG) production. A quantitative real-time PCR analysis revealed that GC-Ra mRNA was expressed more strongly in the mid-luteal stage (days 8-12) than in the other stages. In contrast to GC-Ra mRNA expression, 11-HSD1 mRNA expression was greater in the follicular stage than in the other stages, whereas 11-HSD2 mRNA expression was lowest in the follicular stage. The activity of 11-HSD1 was greater in the follicular stage and estrus than in the other stages and was lowest in the mid-luteal stage. Cortisone was dosedependently converted to cortisol in the cultured endometrial tissue. Although cortisol did not affect either the basal or OT-stimulated production of PGs in the cultured epithelial cells, the production of PGs stimulated by TNFa in the stromal cells was suppressed by cortisol (P!0 . 05). Cortisol suppressed basal prostaglandin (PG)F2a without affecting basal PGE2 production in the stromal cells. The overall results suggest that the level of cortisol is locally regulated in bovine endometrium throughout the estrous cycle by 11-HSD1, and that cortisol could act as a luteoprotective factor by selectively suppressing luteolytic PGF2a production in bovine endometrium.

Effects of Cortisol on Pregnancy Rate and Corpus Luteum Function in Heifers: An <i>In Vivo</i> Study

“…We have previously shown that cortisol inhibits basal PGF 2α production in nonpregnant bovine endometrial stromal cells, whereas it does not affect PGF 2α production in epithelial cells in vitro [8]. This in vitro study suggests that cortisol could mainly act as an antiluteolytic factor suppressing PGF 2α production in the bovine endometrium.…”

“…On the other hand, treatment with metyrapone prolonged the life span of the CL, and luteolysis did not occur until Day 30 post ovulation. The above findings suggest that cortisol differently modulates the life span of the CL depending on physiological status of heifers (pregnant vs. nonpregnant).We have previously shown that cortisol inhibits basal PGF 2α production in nonpregnant bovine endometrial stromal cells, whereas it does not affect PGF 2α production in epithelial cells in vitro [8]. This in vitro study suggests that cortisol could mainly act as an antiluteolytic factor suppressing PGF 2α production in the bovine endometrium.…”

“…Cortisol, an active GC, is an anti-inflammatory agent that acts to modulate the production and action of cytokines and prostaglandins required for ovulation, luteolysis, embryo implantation, fetal growth and placental development [3,7]. It is synthesized from cholesterol in the adrenal cortex and is locally regulated by 11β-hydroxysteroid dehydrogenases (11β-HSDs) [8]. The biological action of GCs is mediated through the activation of intracellular GR receptors (GC-R).…”

“…Access of GCs to GC receptors in target tissues is regulated by two 11β-HSDs, bidirectional 11β-HSD type 1 (11β-HSD1) that mainly converts cortisone to active cortisol [11] and 11β-HSD type 2 (11β-HSD2) that inactivates cortisol to cortisone [12]. Although both 11β-HSDs and GC receptors are expressed in the bovine corpus luteum (CL) [13,14] and endometrium [8] throughout the estrous cycle and early pregnancy [15], the role of GC in regulating CL function is still controversial.Our previous in vitro studies have suggested that cortisol suppresses tumor necrosis factor α (TNFα)-stimulated prostaglandin (PG) F 2α production in endometrial stromal cells [8] and inhibits apoptosis of cultured luteal cells induced by TNFα and interferon-γ (IFNG) [13]. Based on the results of in vitro studies, it seems that cortisol plays a role in preventing excessive uterine PGF 2α production and protecting the CL against apoptosis in nonpregnant cattle [13,16].…”

“…Access of GCs to GC receptors in target tissues is regulated by two 11β-HSDs, bidirectional 11β-HSD type 1 (11β-HSD1) that mainly converts cortisone to active cortisol [11] and 11β-HSD type 2 (11β-HSD2) that inactivates cortisol to cortisone [12]. Although both 11β-HSDs and GC receptors are expressed in the bovine corpus luteum (CL) [13,14] and endometrium [8] throughout the estrous cycle and early pregnancy [15], the role of GC in regulating CL function is still controversial.…”