scholarly journals In Vivo Levels of Prostaglandin F2α, E2 and Prostacyclin in the Corpus Luteum of Pregnant and Pseudopregnant Rats1

1990 ◽  
Vol 42 (5-6) ◽  
pp. 792-800 ◽  
Author(s):  
Jan Olofsson ◽  
Ensio Norjavaara ◽  
Gunnar Selstam
2010 ◽  
Vol 24 (3) ◽  
pp. 632-643 ◽  
Author(s):  
Edward Arvisais ◽  
Xiaoying Hou ◽  
Todd A. Wyatt ◽  
Koumei Shirasuna ◽  
Heinrich Bollwein ◽  
...  

Abstract Little is known about the early intracellular events that contribute to corpus luteum regression. Experiments were designed to determine the effects of prostaglandin F2α (PGF2α) on phosphatidylinositol-3-kinase (PI3K)/Akt signaling in the corpus luteum in vivo and in vitro. Treatment of midluteal-phase cows with a luteolytic dose of PGF2α resulted in a rapid increase in ERK and mammalian target of rapamycin (mTOR)/p70 ribosomal protein S6 kinase (p70S6K1) signaling and a rapid suppression of Akt phosphorylation in luteal tissue. In vitro treatment of primary cultures of luteal cells with PGF2α also resulted in an increase in ERK and mTOR/p70S6K1 signaling and a diminished capacity of IGF-I to stimulate PI3K, Akt, and protein kinase C ζ activation. Accounting for the reductions in PI3K and Akt activation observed in response to PGF2α treatment, we found that PGF2α promoted the phosphorylation of serine residues (307, 612, 636) in the insulin receptor substrate 1 (IRS1) peptide sequence in vivo and in vitro. Serine phosphorylation of IRS1 was associated with reduced formation of IGF-I-stimulated IRS1/PI3Kp85 complexes. Furthermore, treatment with inhibitors of the MAPK kinase 1/ERK or mTOR/p70S6K1 signaling pathways prevented PGF2α-induced serine phosphorylation of IRS1 and abrogated the inhibitory actions of PGF2α on Akt activation. Taken together, these experiments provide compelling evidence that PGF2α treatment stimulates IRS1 serine phosphorylation, which may contribute to a diminished capacity to respond to IGF-I. It seems likely that the rapid changes in phosphorylation events are among the early events that mediate PGF2α-induced corpus luteum regression.


Endocrinology ◽  
2003 ◽  
Vol 144 (8) ◽  
pp. 3301-3305 ◽  
Author(s):  
Carlos Stocco ◽  
Jean Djiane ◽  
Geula Gibori

Abstract It is well established that prolactin (PRL) sustains, whereas prostaglandin F2α (PGF2α) curtails, progesterone production by the rodent corpus luteum (CL). We have previously shown that PGF2α inhibits the expression of several luteal genes stimulated by PRL, whereas it stimulates other genes inhibited by this hormone. We have also found that PGF2α stimulation of 20α-hydroxysteroid dehydrogenase (20αHSD), an enzyme that catabolizes progesterone, at the end of pregnancy is accompanied by a dramatic decrease in PRL receptor (PRL-R) expression. These findings, and the fact that the factors that inhibit PRL-R are not known, led us to examine in vivo whether the decline in PRL-R at the end of pregnancy is due to PGF2α and to also find out whether PGF2α opposes PRL action by inhibiting PRL-R expression. Using the PGF2α receptor (PGF2α-R) knockout, we examined whether the absence of the PGF2α-R prevents the decline in the expression of both the short and long forms of the PRL-R in the CL. We found that, in sharp contrast to the wild-type mice, in which both forms of the PRL-R decline to low levels between d 18–20 of pregnancy, expression of these receptors remained elevated in the PGF2α-R null mice. Furthermore, administration of PGF2α to pregnant rats inhibited PRL-R expression. Time-course analysis revealed that PGF2α treatment decreases both isoforms of PRL-R within 1 h of treatment in vivo, whereas its stimulatory effect on 20αHSD expression was further delayed. Similar results were obtained with luteinized granulosa cells in culture. To examine whether the decline in PRL-R is involved/necessary for PGF2α action, cells were transfected with a constitutively active PRL-R. The expression of this receptor did not prevent PGF2α effect on PRL-R or 20αHSD expression. Taken together, these results demonstrate that PGF2α inhibits the expression of the PRL-R and that the decline in both forms of the PRL-R that occurs at the end of pregnancy in the CL is due to PGF2α. The results further suggest that PGF2α-mediated stimulation of 20αHSD is independent from PGF2α inhibition of PRL signaling in luteal cell.


Reproduction ◽  
2004 ◽  
Vol 128 (2) ◽  
pp. 189-195 ◽  
Author(s):  
Koumei Shirasuna ◽  
Hitomi Asaoka ◽  
Tomas J Acosta ◽  
Missaka P B Wijayagunawardane ◽  
Masayuki Ohtani ◽  
...  

Prostaglandin (PG) F2α released from the uterus in a pulsatile fashion is essential to induce regression of the corpus luteum (CL) in the cow. In addition to the uterus, the CL has also been recognized as a site of PGF2α production. Therefore, this study aimed to determine the detailed dynamics of the releasing profile of CL-derived PGF2α together with uterus-derived PGF2α during spontaneous luteolysis in the cow. Non-lactating Holstein cows (n = 6) were surgically implanted with a microdialysis system (MDS) on day 15 (oestrus = day 0) of the oestrous cycle. Simultaneously, catheters were implanted to collect ovarian venous plasma ipsilateral to the CL as well as jugular venous plasma. The concentrations of PGF2α, 13,14-dihydro-15-keto-PGF2α (PGFM) and progesterone in the MDS and plasma samples were determined by enzyme immunoassays. The intra-luteal PGF2α secretion slightly increased after the onset of luteolysis (0 h) and drastically increased from 24 h, and was maintained at high levels towards the following oestrus. Furthermore, PGF2α was released from the CL into the ovarian vein in a pulsatile manner during spontaneous luteolysis. Also, the fact that intra-luteal secretion of PGF2α and PGFM showed a positive correlation indicates the existence of a local metabolic pathway for PGF2α in the CL. In conclusion, the present study clarified the real-time dynamics of uterus-derived PGF2α and CL-derived PGF2α during spontaneous luteolysis in the cow, and gives the first in vivo evidence that the CL releases PGF2α during spontaneous luteolysis in the cow. Although the physiological relevance of CL-derived PGF2α appears to be restricted to a local role as an autocrine/paracrine factor in the CL, overall results support the concept that the local release of PGF2α within the regressing CL amplifies the luteolytic action of PGF2α from the uterus.


Endocrinology ◽  
2011 ◽  
Vol 152 (7) ◽  
pp. 2797-2805 ◽  
Author(s):  
Wenxiang Luo ◽  
Francisco J. Diaz ◽  
Milo C. Wiltbank

This study tested the hypotheses that prostaglandin (PG) F2α increases expression of genes related to recruitment of leukocytes in mature but not early corpus luteum (CL) and that insensitivity to PGF2α action in early CL is dependent on high intraluteal progesterone (P4) concentrations. Experiment 1 examined early (0.5 h) and late (10 h) in vivo effects of PGF2α on mature (d 17 of pseudopregnancy) and early (d 9) porcine CL. Real-time PCR was used to measure mRNA for chemokines (IL8, CXCL2, CCL2, CCL8, CCL4, CCL11) and chemokine receptors (CCR1, CCR2, CXCR2, CCR5). Western blotting was used to measure protein expression and phosphorylation of nuclear factor-κB proteins. Treatment with PGF2α for 10 h increased mRNA for almost all of these genes (all expect CXCL2 and CCL11) in d 17 CL but not d 9 CL. Treatment with PGF2α also led to greater phosphorylation of nuclear factor-κB-1A protein in d 17 than d 9 CL. Experiment 2 had a 2 × 2 factorial design with d 9 gilts treated or not treated with epostane (3β-hydroxysteroid dehydrogenase inhibitor to suppress intraluteal P4) and treated or not treated with PGF2α. Treatment with PGF2α (10 h) or epostane alone did not induce expression of any of these genes in d 9 CL. However, PGF2α + epostane increased expression of all of these genes except CCL11. In conclusion, PGF2α increases mRNA for chemokines and chemokine receptors in mature CL with similar PGF2α effects induced in early CL if intraluteal P4 is suppressed prior to PGF2α treatment.


2004 ◽  
Vol 82 (6) ◽  
pp. 363-371 ◽  
Author(s):  
R M Narayansingh ◽  
M Senchyna ◽  
M M Vijayan ◽  
J C Carlson

In this study we examined the mechanism of corpus luteum (CL) regression by measuring changes in expression of prostaglandin G/H synthase-1 (PGHS-1) and -2 (PGHS-2) in day 4 CL and inducible heat shock protein 70 (HSP-70) in day 4 and day 9 CL of immature superovulated rats. The rats were superovulated and treated with 500 µg of prostaglandin F2α (PGF2α) on day 4 or day 9 after CL formation. Ovaries and serial blood samples were removed during the 24-hour period following treatment. Plasma progesterone was determined by radioimmunoassay while mRNA abundance and protein expression were assessed by semiquantitative RT-PCR and immunoblot analysis, respectively. One hour after PGF2α, both day 4 and day 9 rats exhibited a significant decrease in progesterone secretion; however, there was a greater decrease in day 9 rats. In ovarian samples removed on day 4, there was a significant increase in mRNA for PGHS-2 at 1 hour after PGF2α. PGHS-1 mRNA content remained unchanged. Immunoblot analyses showed an increase in PGHS-2 protein expression only at 8 h. There were no changes in PGHS-1 protein expression. In day 9 rats, ovarian HSP-70 protein levels increased by 50% after PGF2α injection; however, on day 4 there was no change in expression of this protein over the sampling period. These results suggest that expression of PGHS-2 may be involved in inhibiting progesterone production and that expression of HSP-70 may be required for complete CL regression in the rat.Key words: rat, prostaglandin F2α, corpus luteum, prostaglandin G/H synthase, heat shock protein-70.


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