Interaction between oxytocin and prostaglandin F2 alpha during luteal regression and early pregnancy in sheep

1992 ◽  
Vol 4 (3) ◽  
pp. 321 ◽  
Author(s):  
G Jenkin

The pulsatile release of oxytocin from the corpus luteum in the sheep is responsible for the pulsatile release of prostaglandin F2 alpha (PGF2 alpha) from the uterus at luteolysis. It has been proposed that PGF2 alpha also reinforces this process by stimulating the release of oxytocin from the corpus luteum. It is, however, unlikely that PGF2 alpha is the major stimulus for oxytocin release at this time. Although the stimulus for the pulsatile release of oxytocin from the corpus luteum appears to reach the ovary from the peripheral circulation, the nature of the stimulus is unknown. Pulses of oxytocin originating from the corpus luteum have also been observed during early pregnancy, but the release of PGF2 alpha, in response to this signal, is abrogated in some way by ovine trophoblast protein-1 (oTP-1). This protein has been shown to inhibit endometrial prostaglandin production and to decrease the amount of PGF2 alpha released in response to oxytocin. Reduction of uterine oxytocin receptor concentrations by conceptus secretory proteins or by interferons related to oTP-1 remains equivocal. Inhibition of uterine oxytocin receptors is, however, probably the major mechanism that prevents luteal regression during early pregnancy. In cyclic sheep the specific inhibition of uterine oxytocin receptors by 1-deamino-2-D-Try (oET)-4-Thr-8-Orn-oxytocin (CAP), a synthetic oxytocin receptor antagonist, inhibits luteal regression and suppresses pulsatile, but not basal, secretion of uterine PGF2 alpha. Thus, the effects of CAP directly parallel the endocrinological changes that occur in early pregnancy in the sheep.

Author(s):  
Jéssica N Drum ◽  
Milo C Wiltbank ◽  
Pedro L J Monteiro ◽  
Alexandre B Prata ◽  
Rodrigo S Gennari ◽  
...  

Abstract Circulating prostaglandin F2α metabolite (PGFM) after an oxytocin challenge was evaluated throughout the first 2 months of pregnancy in lactating Holstein cows. On day 11, 18, and 25 after artificial insemination (AI), and on days 32, 39, 46, 53, and 60 of pregnancy, cows were challenged with 50 IU oxytocin, i.m. Blood was collected before (0 min), 30, 60, 90, and 120 min after oxytocin for plasma PGFM concentrations. Ultrasound evaluations were performed for pregnancy diagnosis on day 32–60 post-AI. Nonpregnant (NP) cows on day 18 were designated by a lack of interferon-stimulated genes in peripheral blood leukocytes and Pregnant (P) based on day 32 ultrasound. On day 11, P and NP were similar with low PGFM and no effect of oxytocin on PGFM. On day 18, oxytocin increased PGFM (3-fold) in NP with little change in P cows. Comparing only P cows from day 11 to 60, basal circulating PGFM increased as pregnancy progressed, with day 11 and 18, lower than all days from day 25 to 60 of pregnancy. Oxytocin-induced PGFM in P cows on day 25 was greater than P cows on day 18 (2.9-fold). However, oxytocin-induced PGFM was lower on day 25 compared to day 53 and 60, with intermediate values on day 32, 39, and 46 of pregnancy. Thus, the corpus luteum (CL) of early pregnancy (day 11, 18) is maintained by suppression of PGF, as reflected by suppressed PGFM in this study. However, during the second month of pregnancy, uterine PGF secretion was not suppressed since basal PGFM and oxytocin-induced PGFM secretion were elevated. Apparently, mechanisms other than suppression of oxytocin receptors maintain CL after day 25 of pregnancy.


1996 ◽  
Vol 150 (3) ◽  
pp. 473-478 ◽  
Author(s):  
G E Mann ◽  
J H Payne ◽  
G E Lamming

Abstract In intact cyclic ewes intrauterine infusion of conceptus secretory proteins results in the suppression of both endometrial oxytocin receptor concentrations and oxytocin-induced prostaglandin F2α release. However, similar infusion in progesterone-treated ovariectomized ewes, while suppressing endometrial oxytocin receptors, does not fully inhibit oxytocin-induced prostaglandin F2α release. To examine whether this anomaly resulted from an inadequate simulation of the luteal phase in the ovariectomized ewe treated with progesterone alone, the effects of additional treatment with two other ovarian hormones, oestradiol-17β and oxytocin, was investigated. Rather than permitting conceptus secretory protein to successfully inhibit oxytocin-induced prostaglandin F2α release, treatment with oestradiol-17β in addition to progesterone actually resulted in an advancement in the timing of release. However, treatment with oxytocin, alone or in combination with oestradiol, permitted the full inhibition of oxytocin-induced prostaglandin F2α release. To confirm that this effect did not result from the action of oxytocin alone, independently of the action of conceptus secretory protein, a second experiment was undertaken using a similar protocol but without the infusion of conceptus secretory protein. In this situation, oxytocin-induced prostaglandin F2α release was only partially inhibited suggesting that both luteal oxytocin and conceptus secretory proteins are necessary to facilitate the full inhibition of luteolysis during early pregnancy in the ewe. Journal of Endocrinology (1996) 150, 473–478


1992 ◽  
Vol 4 (3) ◽  
pp. 313 ◽  
Author(s):  
RJ Fairclough ◽  
TM Lau

Uterine oxytocin receptors have been shown to play a major role in the regulation of uterine prostaglandin F2 alpha release during the oestrous cycle and early pregnancy in sheep. The concentration of endometrial oxytocin receptors increases sharply from around Day 13 of the oestrous cycle to reach a maximum between Days 15 and 16. The high concentration of endometrial oxytocin receptors at this time coincides with the release of endogenous uterine prostaglandin F2 alpha during luteal regression and the maximum uterine prostaglandin F2 alpha response to an oxytocin stimulus. The concentration of uterine oxytocin receptors appears to be regulated by both progesterone and oestradiol. Studies in ovariectomized ewes have shown that initially progesterone lowers the concentration of endometrial oxytocin receptors, but after prolonged treatment with progesterone the concentration of oxytocin receptors increases; this suggests that the uterine-PGF2 alpha response to oxytocin has become refractory to the inhibitory effects of progesterone. The concentration of endometrial oxytocin receptors is also lowered by short-term oestradiol treatment. However, oestrogen treatment of ewes after long-term treatment with progesterone does not result in an increase in the concentration of oxytocin receptors following the cessation of progesterone treatment. On the basis of these and other data it is proposed that in the normal oestrous cycle the concentration of endometrial oxytocin receptors is initially depressed by both oestradiol and progesterone but that the marked increase in the concentration of oxytocin receptors over Days 13-16 of the cycle is due primarily to the withdrawal of the inhibitory influence of progesterone alone. During early pregnancy the release of uterine prostaglandin F is suppressed.(ABSTRACT TRUNCATED AT 250 WORDS)


1992 ◽  
Vol 4 (3) ◽  
pp. 289 ◽  
Author(s):  
CW Weems ◽  
DL Vincent ◽  
YS Weems

Pregnancy does not prevent the local transfer or accumulation of prostaglandin F2 alpha (PGF2 alpha) by the corpus luteum (CL), the number of receptors for PGF2 alpha or the binding of PGF2 alpha to the CL. However, the conceptus does depress the response of the CL to PGF2 alpha during early pregnancy. PGE1 and PGE2 appear to be blood-borne antiluteolysins that are delivered locally to prevent the actions of PGF2 alpha during early pregnancy, since they prevent luteolysis only when given by chronic intrauterine infusion adjacent to the ovary with the CL. The concentrations of PGE1 and PGE2 in the endometrium and PGE2 in uterine venous plasma increase during early pregnancy. A Day 10 embryo transferred to a Day 6 progestagen-primed recipient ewe advances the time at which PGE2 is secreted. The uterine venous PGE/PGF2 alpha ratio is 12:1 at midgestation, and exogenous PGF2 alpha increases the placental secretion of oestradiol-17 beta. This is followed by increases in PGE secretion when endogenous PGF2 alpha increases. Both oestradiol-17 beta and PGE may protect placental secretion of progesterone from PGF2 alpha, since PGF2 alpha causes the CL to regress but does not affect placental progesterone or pregnancy in the presence or absence of the ovary.


2021 ◽  
Vol 54 (1) ◽  
Author(s):  
Meeti Punetha ◽  
Sai Kumar ◽  
Avishek Paul ◽  
Bosco Jose ◽  
Jaya Bharati ◽  
...  

Abstract Background PGF2α is essential for the induction of the corpus luteum regression which in turn reduces progesterone production. Early growth response (EGR) proteins are Cys2-His2-type zinc-finger transcription factor that are strongly linked to cellular proliferation, survival and apoptosis. Rapid elevation of EGR1 was observed after luteolytic dose of PGF2α. EGR1 is involved in the transactivation of many genes, including TGFβ1, which plays an important role during luteal regression. Methods The current study was conducted in buffalo luteal cells with the aim to better understand the role of EGR1 in transactivation of TGFβ1 during PGF2α induced luteal regression. Luteal cells from mid stage corpus luteum of buffalo were cultured and treated with different doses of PGF2α for different time durations. Relative expression of mRNAs encoding for enzymes within the progesterone biosynthetic pathway (3βHSD, CYP11A1 and StAR); Caspase 3; AKT were analyzed to confirm the occurrence of luteolytic event. To determine if EGR1 is involved in the PGF2α induced luteal regression via induction of TGFβ1 expression, we knocked out the EGR1 gene by using CRISPR/Cas9. Result The present experiment determined whether EGR1 protein expression in luteal cells was responsive to PGF2α treatment. Quantification of EGR1 and TGFβ1 mRNA showed significant up regulation in luteal cells of buffalo at 12 h post PGF2α induction. In order to validate the role of PGF2α on stimulating the expression of TGFβ1 by an EGR1 dependent mechanism we knocked out EGR1. The EGR1 ablated luteal cells were stimulated with PGF2α and it was observed that EGR1 KO did not modulate the PGF2α induced expression of TGFβ1. In PGF2α treated EGR1 KO luteal cell, the mRNA expression of Caspase 3 was significantly increased compared to PGF2α treated wild type luteal cells maintained for 12 h. We also studied the influence of EGR1 on steroidogenesis. The EGR1 KO luteal cells with PGF2α treatment showed no substantial difference either in the progesterone concentration or in StAR mRNA expression with PGF2α-treated wild type luteal cells. Conclusion These results suggest that EGR1 signaling is not the only factor which plays a role in the regulation of PGF2α induced TGFβ1 signaling for luteolysis.


2019 ◽  
Vol 101 (1) ◽  
pp. 76-90 ◽  
Author(s):  
Megan A Mezera ◽  
Caleb S Hamm ◽  
Caio A Gamarra ◽  
Rodrigo S Gennari ◽  
Alexandre B Prata ◽  
...  

Abstract Mechanisms of bovine corpus luteum (CL) maintenance during the second month of pregnancy have not been adequately investigated, despite significant reproductive losses. In the first month, interferon-tau is believed to suppress oxytocin-stimulated prostaglandin F2α (PGF) production, yet there are conflicting reports of circulating PGF metabolite (PGFM). In this study, characterization of PGFM and P4 occurred through continuous bihourly blood sampling in cows undergoing CL regression (day 18–21, n = 5), and during the first (day 18–21, n = 5) and second month (day 47–61; n = 16) of pregnancy. Cattle in the second month were assigned to control (n = 8) or oxytocin treatment (n = 8; three pulses to mimic luteolysis) to evaluate if oxytocin receptors were active. All cows but one (which had elevated PGFM prior to oxytocin treatment) maintained the pregnancy. Basal PGFM concentrations were low (11.6 ± 0.7 pg/mL) in the first month but increased 2.54-fold in the second month. Few (0.26 ± 0.12 pulses/day) PGFM pulses with low peak concentrations (28.8 ± 3.1 pg/mL) were observed during the first month of pregnancy, similar to cows not undergoing regression. However, in the second month, frequency (1.10 ± 0.26 pulses/day) and peak concentration (67.2 ± 5.0 pg/mL) of PGFM pulses increased, displaying similar frequency but lower peak PGFM than seen in regression (1.44 ± 0.14 pulses/day; 134.5 ± 18.9 pg/mL). Oxytocin treatment increased likelihood of PGFM pulses post-treatment and increased peak concentration (89.7 ± 10.1 pg/mL) in cows during the second month. Thus, cows have more PGFM pulses during second than first month of pregnancy, possibly induced by endogenous oxytocin, indicating suppression of PGF production is an important mechanism for CL maintenance during first but not second month of pregnancy.


1993 ◽  
Vol 10 (2) ◽  
pp. 185-192 ◽  
Author(s):  
M A Mirando ◽  
J P Harney ◽  
Y Zhou ◽  
T F Ogle ◽  
T L Ott ◽  
...  

ABSTRACT This study determined whether twice-daily intrauterine injections of ovine conceptus secretory proteins (oCSP) containing type-I trophoblast interferon (25 μg/uterine horn) from day 11 to day 15 post-oestrus (oestrus = day 0) could alter the binding capacities of endometrial receptors for oxytocin, progesterone and oestrogen in cyclic ewes when compared with control ewes receiving serum protein (SP) injections. Injections of oCSP on days 11–15 post-oestrus decreased concentrations of oestrogen receptors (P<0·06), oestrogen receptor mRNA (P<0·05) and progesterone receptors (P<0·08) in endometrium on day 16 when compared with SP-infused control ewes, which were undergoing corpus luteum regression on days 14–16. Injection of oCSP also decreased the number (P<0·10) and affinity (P<0·06) of oxytocin receptors. Inositol phosphate formation induced in the endometrium on day 16 by 100 nm oxytocin in vitro was highly correlated with the concentration (r≥0·93, P<0·001) and Kd (r= –0·91, P<0·01) of oxytocin receptors in SP-infused ewes, but was not as highly correlated with concentration (r≤0·83, P<0·06) and Kd (r≤ –0·40, P>0·40) of oxytocin receptors in oCSP-infused ewes. This indicates that oCSP disrupted the relationship between oxytocin receptor binding and oxytocin-induced activation of its second messenger system. These results indicate that antiluteolytic type-I trophoblast interferon may prevent oxytocininduced luteolytic pulsatile secretion of prostaglandin F2α during maternal recognition of pregnancy in sheep, by reducing the synthesis and affinity of endometrial oxytocin receptors. Inhibition of other components of the oxytocin receptor—phospholipase C system by ovine trophoblast interferon may also be involved in reducing endometrial responsiveness to oxytocin. Ovine trophoblast interferon may inhibit the synthesis of endometrial oestrogen receptors to inhibit responsiveness to oxytocin during early pregnancy in ewes.


1992 ◽  
Vol 4 (3) ◽  
pp. 307 ◽  
Author(s):  
WJ Silvia

Changes in the ability of the uterus to secrete prostaglandin F2 alpha (PGF2 alpha) in response to oxytocin may play a critical role in determining when endogenous secretion of PGF2 alpha begins. The cellular mechanisms that regulate uterine secretion of PGF2 alpha in response to oxytocin have not been completely defined. Several intracellular components that may contribute to this regulation have been studied, including phospholipase C (PLC), prostaglandin H endoperoxide synthase (PGS) and receptors for oxytocin. All of these components change during the oestrous cycle and are associated with the development of uterine secretory responsiveness to oxytocin. Progesterone appears to play the principal role in regulating oxytocin receptors, PLC and PGS. The conceptus appears to suppress the increase in receptors for oxytocin and PLC activity that typically occurs around the time of luteal regression.


1988 ◽  
Vol 117 (2) ◽  
pp. R5-R8 ◽  
Author(s):  
J. L. Vallet ◽  
F. W. Bazer ◽  
C.J. Ashworth ◽  
H. M. Johnson ◽  
C. H. Pontzer

ABSTRACT A radioimmunoassay has been developed for quantitation of ovine trophoblast protein-1 (oTP-1), a sheep conceptus secretory protein which allows for maintenance of the corpus luteum during early pregnancy. The assay was validated for dialysed and undialysed culture medium and pregnant uterine flushings ranging from no dilution (neat) to dilutions of 1:2500 for dialysed media, 1:100-1:1000 for undialysed media and 1:50-1:1000 for pregnant uterine flushings. The assay accurately measured oTP-1 added to undiluted and diluted dialysed and undialysed culture media and pregnant uterine flushings. No cross-reaction was detectable for bovine α or γ interferon, bovine calmodulin, feline conceptus secretory proteins, equine conceptus secretory proteins, porcine conceptus secretory proteins, bovine conceptus secretory proteins and proteins in a uterine flushing collected from a non-pregnant ewe. Immunoreactivity in the assay matched that for oTP-1 throughout oTP-1 purification. This assay is the first validated assay which may be used to quantitate production of oTP-1 in culture or content of oTP-1 in uterine flushings.


1976 ◽  
Vol 56 (4) ◽  
pp. 595-651 ◽  
Author(s):  
E. W. Horton ◽  
N. L. Poyser

To summarize luteal function during pregnancy briefly, there are physiological processes initiated by the embryo and/or conceptus in early pregnancy that serve to prolong the life-span of the corpus luteum. Some of these processes are well defined, but others remain more obscure. The corpus luteum is maintained in a functional state throughout pregnancy (at least in those species described in this review), even though in several species progesterone production by the corpus luteum is not required after the first third of the gestational period. The cessation of secretory function by the corpus luteum of pregnancy at the end of gestation is apparently actively induced. There is evidence in some species (especially the goat) that this is due to PGF2alpha released from the uterus or placenta. It is concluded that the occurrence of luteal regression in several species of mammal can be attributed to the physiological release of PGF2alpha from both the pregnant and nonpregnant uterus.


Sign in / Sign up

Export Citation Format

Share Document