Abstract. To determine whether glucocorticoids affect the function of the bovine corpus luteum (CL) during the estrous cycle and early pregnancy, we examined the effects of exogenous cortisol or reduced endogenous cortisol on the secretion of progesterone (P4) and on pregnancy rate. In preliminary experiments, doses of cortisol and metyrapone (an inhibitor of cortisol synthesis) were established (n=33). Cortisol in effective doses of 10 mg blocked tumor necrosis factor-induced prostaglandin F 2α secretion as measured by its metabolite (PGFM) concentrations in the blood. Metyrapone in effective doses of 500 mg increased the P4 concentration. Thus, both reagents were then intravaginally applied in the chosen doses daily from Day 15 to 18 after estrus (Day 0) in noninseminated heifers (n=18) or after artificial insemination (n=36). Pregnancy was confirmed by transrectal ultrasonography between Days 28-30 after insemination. Plasma concentrations of P4 were lower in cortisol-treated heifers than in control heifers on Days 17 and 18 of the estrous cycle (P<0.05). However, the interestrus intervals were not different between control and cortisol-treated animals (P>0.05). Moreover, metyrapone increased P4 and prolonged the CL lifespan in comparison to control animals (P<0.05). Interestingly, in inseminated heifers, cortisol increased the pregnancy rate (75%) compared with control animals (58%), whereas metyrapone reduced the pregnancy rate to 16.7% (P<0.05). The overall results suggest that cortisol, depending on the physiological status of heifers (pregnant vs. nonpregnant), modulates CL function by influencing P4 secretion. Cortisol may have a positive influence on CL function during early pregnancy, leading to support of embryo implantation and resulting in higher rates of pregnancy in heifers. Key words: Cattle, Cortisol, Early pregnancy, Estrous cycle, Progesterone (J. Reprod. Dev. 58: [223][224][225][226][227][228][229][230] 2012) G lucocorticoids (GCs) are involved in many physiological processes [1,2], including female reproductive functions [3] in rabbits [4], ewes [5] and humans [6]. 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). Two isoforms of GC-R, GC-Rα and GC-Rβ, have been identified [9,10]. 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 ea...