Control of Bovine Uterine Prostaglandin F2α Release in Vitro1

236

172

To determine the physiological significance of tumor necrosis factor alpha (TNFalpha) in the regulation of luteolytic prostaglandin (PG) F(2alpha) release by the bovine endometrium, the effect of TNF-alpha on PGF(2alpha) output by the endometrial tissues in vitro was investigated and compared with the effect of oxytocin (OT). Furthermore, the presence of specific receptors for TNFalpha in the bovine endometrium during the estrous cycle was determined. Endometrial slices (20-30 mg) taken from six stages of the estrous cycle (estrus: Day 0; early I: Days 2-3; early II: Days 5-6; mid-: Days 8-12; late: Days 15-17; and follicular: Days 19-21), as determined by macroscopic examination of the ovaries and uterus, were exposed to TNFalpha (0.06-6 nM) and/or OT (100 nM). OT stimulated PGF(2alpha) output at the follicular stage and at estrus (P < 0.001), but not at the late luteal stage. On the other hand, the stimulatory effects of TNFalpha on PGF(2alpha) output were observed not only at the follicular stage but also at the late luteal stage (P < 0.001). When the endometrial tissues at late luteal stage were simultaneously exposed to TNFalpha (0.6 nM) and OT (100 nM), the stimulatory effect on PGF(2alpha) output was higher than the effect of TNFalpha or OT alone (P < 0.05). Specific binding of TNFalpha to the bovine endometrial membranes was observed throughout the estrous cycle. The concentration of TNF-alpha receptor at the early I luteal stage was less than the concentrations at other luteal stages (P < 0.01). The dissociation constant (K(d)) values of the endometrial membranes were constant during the estrous cycle. The overall results lead us to hypothesize that TNFalpha may be a trigger for the output of PGF(2alpha) by the endometrium at the initiation of luteolysis in cattle.

Section: Discussionsupporting

confidence: 92%

Is Tumor Necrosis Factor α a Trigger for the Initiation of Endometrial Prostaglandin F2α Release at Luteolysis in Cattle?1

Miyamoto

Skarzynski

Okuda

2000

236

172

“…A similar mechanism is probably present in bovine endometrium, since oxytocin induced PI hydrolysis in the present experiment and in a previous study [22]. Moreover, PGF 2 , secretion by endometrial explants from cattle was increased by treatment of endometrium with phorbol 12-myristate 13-acetate [36,37] to mimic protein kinase C activation by diacylglycerol, or with calcium ionophore A23187 [37] to mimic the action of inositol 1,4,5-trisphosphate on intracellular Ca 2+ mobilization.…”

Section: Discussionsupporting

confidence: 89%

Relationships among Endometrial Oxytocin Receptors, Oxytocin-Stimulated Phosphoinositide Hydrolysis and Prostaglandin F2α Secretion in Vitro, and Plasma Concentrations of Ovarian Steroids before and during Corpus Luteum Regression in Cyclic Heifers1

Mirando

Becker

Whiteaker

1993

Oxytocin stimulates secretion of endometrial prostaglandin (PG) F2 alpha and induces endometrial phosphoinositide hydrolysis around the time of regression of the corpus luteum (CL) in cows. This study investigated the relationship between endometrial oxytocin receptors, oxytocin-stimulated phosphoinositide hydrolysis and PGF 2 alpha secretion in vitro, and plasma concentrations of ovarian steroids before and during CL regression in cyclic heifers (i.e., Days 13-19 post-estrus). Reproductive tracts were collected from 16 cyclic heifers on Days 13 (n = 5), 16 (n = 5), and 19 (n = 6). Decreases in mean CL weight (4.7, 4.6, and 3.0 +/- 0.6 g for Days 13, 16, and 19, respectively; p< 0.05) and plasma progesterone (12.2, 10.5, and 4.3 +/- 1.5 ng/ml for Days 13, 16, and 19, respectively; p < 0.01) were detected between Days 16 and 19, indicating that CL regression had been initiated in the group of Day 19 heifers. Mean concentration of plasma estradiol (3.4, 3.8, and 5.6 +/- 1.7 pg/ml for Days 13, 16, and 19, respectively) did not differ significantly (p > 0.5) among days of the estrous cycle. Concentration of endometrial oxytocin receptors increased (p < 0.06) during the estrous cycle (36, 49, and 789 +/- 234 fmol/mg protein on Days 13, 16, and 19, respectively), but the greatest increase (p < 0.05) occurred between Days 16 and 19. Similarly, incorporation of [3H]inositol into endometrial inositol phosphates induced in vitro with 100 nM oxytocin also increased (p < 0.01) during the estrous cycle (5121 vs. 5819, 4529 vs. 7239, and 5888 vs 68,096 +/- 18,564 dpm/g tissue for control vs. oxytocin-treated endometrium on Days 13, 16, and 19, respectively) with the greatest increase (p < 0.01) in responsiveness to oxytocin occurring between Days 16 and 19.(ABSTRACT TRUNCATED AT 250 WORDS)

“…Oxytocin (OT) has been shown to stimulate prostaglandin (PG) F 2 Q release in vivo from the uteri of prepubertal, nonpregnant cyclic, and postpartum cows [1][2][3][4][5] and in vitro in explant cultures of bovine endometrium [6][7][8]. Pretreatment with an OT antagonist inhibited OT-induced release of PGF 2 ,, from the uterus [9], indicating that PGF 2 ,, release was mediated by OT receptors (OTR).…”

Section: Introductionmentioning

confidence: 99%

Oxytocin Induces Prostaglandin F2α Release in Pregnant Cows: Influence of Gestational Age and Oxytocin Receptor Concentrations1

Fuchs

Rollyson

Meyer

et al. 1996

Brahman cows with known breeding dates received i.v. injections of either 10 or 100 IU oxytocin (OT) on Days 50, 150, 250, or 280 of gestation (n = 6 for each stage). Concentrations of the prostaglandin (PG) F2 alpha metabolite, 13,14-dihydro-15-keto-prostaglandin (PGFM), and OT were measured in samples of peripheral plasma collected at 15-min intervals for 1 h before and 1 h after treatment and then at 30-min intervals for 3 h. Plasma progesterone was measured daily for 14 days after OT injections on Days 50 and 250 of gestation. The increase in plasma OT after injection was dose-dependent (p = 0.001) but not affected by stage of gestation. Plasma PGFM increased after OT in a dose- and stage-dependent manner (p = 0.0001). At Day 280, the increase in plasma PGFM after 100 IU OT was sevenfold greater than at Day 50. Plasma progesterone declined significantly during the 7th to 12th days postinjection and returned to normal pregnancy values by the 14th day (4.4 +/- 0.3 ng/ml) except in two cows treated on Day 50 of gestation that later aborted. In these, plasma progesterone was significantly lower, 2.6 +/- 0.1 ng/ml. In a second experiment, the concentration of OT receptors was determined in endometrium collected from purebred Angus or Hereford cows slaughtered on Days 50, 150, 250, and 280 of gestation (n = 3 or 4 at each stage). Endometrial concentrations of OT receptor changed as a function of gestational age, increasing sixfold from Day 50 to Day 280, which was parallel to the increase by OT of plasma PGFM. Thus, endometrial OT receptors are functionally coupled to PGF2 alpha release during pregnancy, and their concentration determines the magnitude of OT-induced PGF2 alpha release during gestation. Consequently, endogenous OT is a factor in the regulation of PGF2 alpha release from the bovine uterus during pregnancy and parturition.