Ovine conceptus secretory proteins and bovine recombinant interferon α1-1 decrease endometrial oxytocin receptor concentrations in cyclic and progesterone-treated ovariectomized ewes

1991 ◽  
Vol 131 (3) ◽  
pp. 475-482 ◽  
Author(s):  
J. L. Vallet ◽  
G. E. Lamming
Keyword(s):  
Serum Proteins ◽  
Oxytocin Receptor ◽  
Placebo Control ◽  
Interferon Α ◽  
Secretory Proteins ◽  
Recombinant Interferon ◽  
Blood Samples ◽  
Progesterone Treatment ◽  
Oxytocin Receptors ◽  
Prostaglandin F

ABSTRACT A series of experiments was performed to determine whether proteins produced by the sheep conceptus (oCSP) during the time of maternal recognition of pregnancy or bovine recombinant interferon α1-1 (brIFN) decrease oxytocin receptor concentrations in the endometrium of cyclic or ovariectomized progesterone-treated ewes. In experiment 1, cyclic ewes received intrauterine infusions of serum proteins (oSP), oCSP or brIFN on days 12, 13 and 14 of the oestrous cycle. Ewes then received an oxytocin challenge (1 μg in 0·9% NaCl), and blood samples were taken just before and every 10 min for 1 h after the challenge; these were measured for 13,14-dihydro-15-ketoprostaglandin F2α (PGFM), the stable metabolite of prostaglandin F2α. Endometrial oxytocin receptor concentrations were then measured. The oCSP and brIFN treatments suppressed both endometrial oxytocin receptor concentrations and oxytocin-induced increases in PGFM concentrations. In experiment 2, ewes were ovariectomized and then pretreated with a fluorogestone acetate-releasing intravaginal device for 10 days followed by oestradiol (25 μg i.m. twice daily for 2 days). Ewes were then treated with progesterone (10 mg i.m. twice daily for 12 days). Ewes received intrauterine infusions of oSP, oCSP and brIFN on days 10, 11 and 12 of progesterone treatment. On the day after the last progesterone treatment, ewes were challenged with oxytocin and blood samples collected to measure PGFM. Endometrial oxytocin receptors were also measured. Treatment with oCSP, but not brIFN, suppressed endometrial concentrations of oxytocin receptor, and neither oCSP nor brIFN altered oxytocin-induced increases in PGFM concentrations. In experiment 3, ewes were ovariectomized and pretreated as in experiment 2 and then received progesterone treatment for 6, 8, 10 or 30 days. On the day after the last progesterone treatment, ewes received an oxytocin challenge and blood samples and endometrium were collected as in experiment 1. Endometrial oxytocin receptors increased sharply between days 8 and 10 and remained raised after 30 days of progesterone treatment. Oxytocin-induced PGFM increased between 8 and 10 days of progesterone treatment, but no response to oxytocin was detected after 30 of progesterone treatment. In experiment 4, ewes were pretreated as in experiment 2 and then treated for 10 days with progesterone and received intrauterine infusions of oCSP, oSP or brIFN placebo control buffer on days 8, 9 and 10. Ewes received oxytocin and blood samples and endometrium were collected as in experiment 1. As in experiment 2, oCSP treatment suppressed oxytocin receptor concentrations but did not affect oxytocin-induced PGFM release. In experiment 5, ewes were treated with steroid hormones as in experiment 4 and then received intrauterine infusions of either brIFN or oSP on days 8, 9 and 10 of progesterone treatment. The brIFN treatment suppressed oxytocin receptor concentrations but did not suppress oxytocin-induced increases in plasma PGFM. We concluded from these experiments that (1) treatment of cyclic ewes with either oCSP or brIFN decreases endometrial oxytocin receptor concentrations and oxytocin-induced increases in PGFM and (2) in progesterone-treated ovariectomized ewes, treatment with oCSP and brIFN suppresses endometrial oxytocin receptor concentrations but does not suppress oxytocin-induced increases in PGFM. Journal of Endocrinology (1991) 131, 475–482

The effect of oxytocin and oestradiol on the action of conceptus secretory protein in progesterone-treated ovariectomized ewes

1996 ◽  
Vol 150 (3) ◽  
pp. 473-478 ◽  
Author(s):  
G E Mann ◽  
J H Payne ◽  
G E Lamming
Keyword(s):  
Early Pregnancy ◽  
Luteal Phase ◽  
Protein A ◽  
Ovarian Hormones ◽  
Secretory Protein ◽  
Oxytocin Receptor ◽  
Additional Treatment ◽  
Secretory Proteins ◽  
Oxytocin Receptors ◽  
Prostaglandin F

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

Regulation of oxytocin, oestradiol and progesterone receptor concentrations in different uterine regions by oestradiol, progesterone and oxytocin in ovariectomized ewes

1996 ◽  
Vol 151 (3) ◽  
pp. 375-393 ◽  
Author(s):  
D C Wathes ◽  
G E Mann ◽  
J H Payne ◽  
P R Riley ◽  
K R Stevenson ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Low Dose ◽  
Progesterone Receptors ◽  
Cell Types ◽  
Oxytocin Receptor ◽  
Luminal Epithelium ◽  
Time Points ◽  
Progesterone Treatment ◽  
Oxytocin Receptors ◽  
Receptor Concentration

Abstract The regulation of oxytocin, oestradiol and progesterone receptors in different uterine cell types was studied in ovariectomized ewes. Animals were pretreated with a progestogen sponge for 10 days followed by 2 days of high-dose oestradiol to simulate oestrus. They then received either low-dose oestradiol (Group E), low-dose oestradiol plus progesterone (Group P) or low-dose oestradiol, progesterone and oxytocin (via osmotic minipump; Group OT). Animals (three to six per time-point) were killed following ovariectomy (Group OVX), at oestrus (Group O) or following 8, 10, 12 or 14 days of E, P or OT treatment. In a final group, oxytocin was withdrawn on day 12 and ewes were killed on day 14 (Group OTW). Oxytocin receptor concentrations and localization in the endometrium and myometrium were measured by radioreceptor assay, in situ hybridization and autoradiography with the iodinated oxytocin receptor antagonist d(CH2)5[Tyr(Me)2,Thr4,Tyr-NH29]-vasotocin. Oestradiol and progesterone receptors were localized by immunocytochemistry. Oxytocin receptors were present in the luminal epithelium and superficial glands of ovariectomized ewes. In Group O, endometrial oxytocin receptor concentrations were high (1346 ± 379 fmol [3H]oxytocin bound mg protein−1) and receptors were also located in the deep glands and caruncular stroma in a pattern resembling that found at natural oestrus. Continuing low-dose oestradiol was unable to sustain high endometrial oxytocin receptor concentrations with values decreasing significantly to 140 ± 20 fmol mg protein−1 (P<0·01), localized to the luminal epithelium and caruncular stroma but not the glands. Progesterone treatment initially abolished all oxytocin receptors with none present on days 8 or 10. They reappeared in the luminal epithelium only between days 12 and 14 to give an overall concentration of 306 ± 50 fmol mg protein−1. Oxytocin treatment caused a small increase in oxytocin receptor concentration in the luminal epithelium on days 8 and 10 (20 ± 4 in Group P and 107 ± 35 fmol mg protein−1 in Group OT, P<0·01) but the rise on day 14 was not affected (267 ± 82 in Group OT and 411 ± 120 fmol mg protein−1 in Group OTW). In contrast, oestradiol treatment was able to sustain myometrial oxytocin receptors (635 ± 277 fmol mg protein−1 in Group O and 255 ± 36 in Group E) and there was no increase over time in Groups P, OT and OTW with values of 61 ± 18, 88 ± 53 and 114 ± 76 fmol mg protein−1 respectively (combined values for days 8–14). Oestradiol receptor concentrations were high in all uterine regions in Group O. This pattern and concentration was maintained in Group E. In all progesterone-treated ewes, oestradiol receptor concentrations were lower in all regions at all time-points. The only time-related change occurred in the luminal epithelium in which oestradiol receptors were undetectable on day 8 but developed by day 10 of progesterone treatment. Progesterone receptors were present at moderate concentrations in the deep glands, caruncular stroma, deep stroma and myometrium in Group O. Oestradiol increased progesterone receptors in the luminal epithelium, superficial glands, deep stroma and myometrium. Progesterone caused the loss of its own receptor from the luminal epithelium and superficial glands and decreased its receptor concentration in the deep stroma and myometrium at all time-points. There was a time-related loss of progesterone receptors from the deep glands of progesterone-treated ewes between days 8 and 14. These results show differences in the regulation of receptors between uterine regions. In particular, loss of the negative inhibition by progesterone on the oxytocin receptor by day 14 occurred only in the luminal epithelium, but is unlikely to be a direct effect of progesterone as no progesterone receptors were present on luminal epithelial cells between days 8 and 14. The presence of oxytocin receptors in the luminal epithelium of ovariectomized ewes suggests that oestradiol is not essential for oxytocin receptor synthesis at this site. Oestradiol was able to sustain its own receptor at all sites, but high circulating progesterone was always inhibitory to oestradiol receptors. In general, oestradiol stimulated progesterone receptors in epithelial cells whereas progesterone abolished its own receptor from epithelial cells over a period of time, but had a lesser effect on stromal cells. The concentration of all three receptors is therefore differentially regulated between different uterine cell types, suggesting the importance of paracrine effects which remain to be elucidated. Journal of Endocrinology (1996) 151, 375–393

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
Keyword(s):  
Corpus Luteum ◽  
Early Pregnancy ◽  
Peripheral Circulation ◽  
Oxytocin Receptor ◽  
Secretory Proteins ◽  
Luteal Regression ◽  
Pulsatile Release ◽  
Major Mechanism ◽  
Prostaglandin F2 Alpha ◽  
Oxytocin Receptors

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.

Changes in progesterone and oestrogen receptor mRNA and protein and oxytocin receptors in endometrium of ewes after intrauterine injection of ovine trophoblast interferon

1993 ◽  
Vol 10 (2) ◽  
pp. 185-192 ◽  
Author(s):  
M A Mirando ◽  
J P Harney ◽  
Y Zhou ◽  
T F Ogle ◽  
T L Ott ◽  
...  
Keyword(s):  
Oestrogen Receptor ◽  
Inositol Phosphate ◽  
Oxytocin Receptor ◽  
Secretory Proteins ◽  
Type I ◽  
Oestrogen Receptors ◽  
Receptor Mrna ◽  
Oxytocin Receptors ◽  
Highly Correlated

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.

scholarly journals Cloprostenol administration in the first week postpartum reduces expression of oxytocin receptors in the endometrium in Holstein-Zebu cows

2017 ◽  
Vol 69 (4) ◽  
pp. 821-829
Author(s):  
A. Camargos ◽  
S. Wohlres-Viana ◽  
I.F. Costa ◽  
L.S. Camargo ◽  
J.C. Ferreira ◽  
...  
Keyword(s):  
Saline Solution ◽  
Solution Treatment ◽  
Prostaglandin F2α ◽  
Oxytocin Receptor ◽  
Endometrial Biopsy ◽  
Crossbred Cows ◽  
Oxytocin Receptors ◽  
Prostaglandin F ◽  
Estrogen Receptor 1 ◽  
Zebu Cows

ABSTRACT The present study investigated the hormonal profile and expression of prostaglandin F2α (PGF2α), oxytocin and estrogen receptors in uterine tissues of postpartum cows treated with cloprostenol. Twenty Holstein-Zebu crossbred cows were treated with saline solution (treatment CONT) or cloprostenol (treatment CLO), both administered two and five days postpartum. Blood samples were collected on days two, seven, 14, 21 and 28 postpartum for progesterone, PGF2α metabolite (PGFM) and estradiol determination, and endometrial biopsy was performed in order to quantify the expression of oxytocin receptor (OXTR), prostaglandin F receptor (PTGFR) and estrogen receptor 1 (ERS1) genes. In the CLO treatment, expression of OXTR was reduced (P<0.05) but no difference (P>0.05) between treatments was found for PTGFR and ERS1 expression. Estrogen concentrations increased progressively until day 14 (P<0.05) and the highest OXTR expression and lowest PTGFR expression were observed on day 14 (P<0.05) in both treatments. Serum PGFM concentrations were high throughout the experiment. In conclusion, cloprostenol administration at days two and five of postpartum seems to reduce OXTR expression in the endometrium in crossbred cows.

Characterization and autoradiographical localization of oxytocin receptors within the ovine endometrium in relation to post-partum corpus luteum function

1991 ◽  
Vol 128 (2) ◽  
pp. 253-NP ◽  
Author(s):  
J. M. Wallace ◽  
P. J. Morgan ◽  
R. Helliwell ◽  
R. P. Aitken ◽  
M. Cheyne ◽  
...  
Keyword(s):  
Post Partum ◽  
Oxytocin Receptor ◽  
Corpora Lutea ◽  
Uterine Endometrium ◽  
Oxytocin Receptors ◽  
High Incidence ◽  
Prostaglandin F ◽  
Group A ◽  
And Control

ABSTRACT The induction of ovulation in early post-partum ewes is associated with a high incidence of premature luteal regression which is independent of the suckling stimulus but dependent on the stage post partum. The aim of the present study was to determine whether oxytocin receptors are present on uterine endometrium early in the luteal phase and hence ascertain whether oxytocin-induced uterine prostaglandin F2α release is a possible mechanism involved in the premature regression of these post-partum corpora lutea. Ovarian and uterine tissues were collected on day 4 of the cycle in ewes induced to ovulate at either 21 or 35 days post partum (n = 4 per group). A further four cyclic ewes were similarly synchronized to ovulate and acted as controls. Corpora lutea from the 21-day post-partum group were significantly (P < 0·01) smaller, had a lower progesterone content and a reduced capacity to secrete progesterone in vitro than corpora lutea from 35-day post-partum or control ewes. A highly specific oxytocin receptor ligand 125I-labelled d(CH2)5[Tyr(Me)2,Thr4,Tyr-NH29]-vasotocin was used to localize and characterize high affinity oxytocin receptors in uterine endometrium (dissociation constant 145 pmol/l). Oxytocin receptor concentrations in endometrium from ewes induced to ovulate at 21 days post partum were on average five-fold higher (P < 0·05) than in 35-day post-partum and control groups. Journal of Endocrinology (1991) 128, 253–260

Allergy of delayed type to recombinant interferon α 2c

1989 ◽  
Vol 20 (2) ◽  
pp. 149-150 ◽  
Author(s):  
Ulf Detmar ◽  
Monika Agathos ◽  
Christoph Nerl
Keyword(s):  
Interferon Α ◽  
Recombinant Interferon

17β-estradiol attenuates exercise-induced neutrophil infiltration in men

2011 ◽  
Vol 300 (6) ◽  
pp. R1443-R1451 ◽  
Author(s):  
Lauren G. MacNeil ◽  
Steven K. Baker ◽  
Ivan Stevic ◽  
Mark A. Tarnopolsky
Keyword(s):  
Membrane Damage ◽  
Neutrophil Infiltration ◽  
Cholesterol Homeostasis ◽  
Control Group ◽  
Placebo Control ◽  
Blood Samples ◽  
Caveolin 1 ◽  
Macrophage Density ◽  
17Β Estradiol ◽  
Exercise Induced

17β-estradiol (E2) attenuates exercise-induced muscle damage and inflammation in some models. Eighteen men completed 150 eccentric contractions after random assignment to placebo (Control group) or E2 supplementation (Experimental group). Muscle biopsies and blood samples were collected at baseline, following 8-day supplementation and 3 h and 48 h after exercise. Blood samples were analyzed for sex hormone concentration, creatine kinase (CK) activity and total antioxidant capacity. The mRNA content of genes involved in lipid and cholesterol homeostasis [forkhead box O1 (FOXO1), caveolin 1, and sterol regulatory element binding protein-2 (SREBP2)] and antioxidant defense (SOD1 and -2) were measured by RT-PCR. Immunohistochemistry was used to quantify muscle neutrophil (myeloperoxidase) and macrophage (CD68) content. Serum E2 concentration increased 2.5-fold with supplementation ( P < 0.001), attenuating neutrophil infiltration at 3 h ( P < 0.05) and 48 h ( P < 0.001), and the induction of SOD1 at 48 h ( P = 0.02). Macrophage density at 48 h ( P < 0.05) and SOD2 mRNA at 3 h ( P = 0.01) increased but were not affected by E2. Serum CK activity was higher at 48 h for both groups ( P < 0.05). FOXO1, caveolin 1 and SREBP2 expression were 2.8-fold ( P < 0.05), 1.4-fold ( P < 0.05), and 1.5-fold ( P < 0.001) and higher at 3 h after exercise with no effect of E2. This suggests that E2 attenuates neutrophil infiltration; however, the mechanism does not appear to be lesser oxidative stress or membrane damage and may indicate lesser neutrophil/endothelial interaction.

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