Systemic and local regulation of oxytocin receptors in the rat uterus, and their functional significance

1983 ◽  
Vol 61 (7) ◽  
pp. 615-624 ◽  
Author(s):  
A.-R. Fuchs ◽  
S. Periyasamy ◽  
M. S. Soloff
Keyword(s):  
Spontaneous Activity ◽  
Estradiol Benzoate ◽  
Inhibitory Effect ◽  
Oxytocin Receptor ◽  
Oxytocin Receptors ◽  
Partial Correlations ◽  
Near Term ◽  
Nuclear Estrogen Receptor ◽  
The Right ◽  
Intact Rats

Rats were made unilaterally pregnant by tying the right oviduct on the day after mating, to compare the oxytocin receptor concentrations in a nondistended, nonpregnant uterine horn with those in a distended, pregnant horn. On day 20, they were subjected to bilateral ovariectomy and indwelling balloons were inserted into both uterine horns. Following ovariectomy, the rats were injected im with either oil, estradiol benzoate (5 μg/rat per 24 h), progesterone (5 mg/rat per 24 h), or estradiol and progesterone together. For comparison, intact rats were studied on days 21 and 22, 24 and 48 h after insertion of the indwelling balloons. Spontaneous uterine activity and the response to increasing amounts of oxytocin were recorded 20–24 h and 44–48 h after surgery, following which the uteri were excised and assayed for oxytocin and estrogen receptors. The oxytocin receptor concentrations in the two horns were different on day 20 before the treatments were begun, the distended pregnant horn having a higher concentration per milligram DNA than the nonpregnant horn. The various treatments always changed the oxytocin receptor concentrations in the same direction; estrogen increased and progesterone inhibited the estrogen-induced rise in oxytocin receptor concentrations. In intact rats, the distention-induced increase in oxytocin receptor concentrations present on day 20 disappeared near term, but in the absence of the ovaries distention of the uterus had a significant influence on the myometrial oxytocin receptor concentrations, potentiating the effect of estrogen. Progesterone selectively inhibited the distention-induced increase in oxytocin receptor concentrations without inhibiting the hypertrophic effect of distention in general. A good correlation between oxytocin receptor numbers and tissue responsiveness was observed in all instances. The changes in spontaneous activity induced by the various treatments were distinct from the changes in oxytocin responsiveness. Estrogen exerted a strong inhibitory action on the activity stimulated by hormone withdrawal, while progesterone had no inhibitory effect. The pregnant distended horn always showed more spontaneous activity than the nonpregnant horn. There was an overall significant correlation between nuclear estrogen receptor and oxytocin receptor concentrations per milligram DNA, although the partial correlations were not significant in all groups (oil and progesterone). It is concluded that ovarian hormones exert the major regulatory influence on myometrial oxytocin receptor concentrations, but other factors including distention modulate their effect.

scholarly journals Localized actions of progesterone in hypothalamus involve oxytocin

1989 ◽  
Vol 86 (17) ◽  
pp. 6798-6801 ◽  
Author(s):  
M Schumacher ◽  
H Coirini ◽  
M Frankfurt ◽  
B S McEwen
Keyword(s):  
Receptor Binding ◽  
Fold Increase ◽  
Ovarian Hormones ◽  
Estradiol Benzoate ◽  
Ventromedial Hypothalamus ◽  
Oxytocin Receptor ◽  
Behavioral Effects ◽  
Female Rat ◽  
Surrounding Area ◽  
Oxytocin Receptors

Two ovarian hormones, estradiol and progesterone, which facilitate mating behavior in the female rat by acting on the ventromedial nuclei (VMN) of the hypothalamus, induce changes in oxytocin receptor binding in this brain region. Estradiol induced a 4-fold increase in the oxytocin receptor binding of the VMN and surrounding area and increased the number and immunostaining of oxytocin fibers in an area lateral to the ventral VMN. Progesterone, in estrogen-primed rats, caused the induced oxytocin receptors to spread over the area containing the oxytocin fibers. Infusion of oxytocin into the ventromedial hypothalamus increased the display of lordosis behavior only in females primed with both estradiol benzoate and progesterone. Thus, the sequential actions of two ovarian hormones bring a neuropeptide and its receptors into register and enable the neuropeptide to exert behavioral effects.

POSSIBLE ROLE OF 5α-ANDROSTANE-3α,17β-DIOL IN THE CONTROL OF FOLLICLE-STIMULATING HORMONE SECRETION IN THE IMMATURE FEMALE RAT

1982 ◽  
Vol 92 (1) ◽  
pp. 37-42 ◽  
Author(s):  
H. M. A. MEIJS-ROELOFS ◽  
P. KRAMER ◽  
L. GRIBLING-HEGGE
Keyword(s):  
Inhibitory Action ◽  
Combined Treatment ◽  
Hormone Secretion ◽  
Inhibitory Effect ◽  
Ovariectomized Rats ◽  
Female Rat ◽  
Immature Rat ◽  
Rat Strain ◽  
Intact Rats

A possible role of 5α-androstane-3α,17β-diol (3α-androstanediol) in the control of FSH secretion was studied at various ages in ovariectomized rats. In the rat strain used, vaginal opening, coincident with first ovulation, generally occurs between 37 and 42 days of age. If 3α-androstanediol alone was given as an ovarian substitute, an inhibitory effect on FSH release was evident with all three doses tested (50, 100, 300 μg/100 g body wt) between 13 and 30 days of age; at 33–35 days of age only the 300 μg dose caused some inhibition of FSH release. Results were more complex if 3α-androstanediol was given in combined treatment with oestradiol and progesterone. Given with progesterone, 3α-androstanediol showed a synergistic inhibitory action on FSH release between 20 and 30 days of age. However, when 3α-androstanediol was combined with oestradiol a clear decrease in effect, as compared to the effect of oestradiol alone, was found between 20 and 30 days of age. Also the effect of combined oestradiol and progesterone treatment was greater than the effect of combined treatment with oestradiol, progesterone and 3α-androstanediol. At all ages after day 20 none of the steroid combinations tested was capable of maintaining FSH levels in ovariectomized rats similar to those in intact rats. It is concluded that 3α-androstanediol might play a role in the control of FSH secretion in the immature rat, but after day 20 the potentially inhibitory action of 3α-androstanediol on FSH secretion is limited in the presence of oestradiol.

Dynamics of oxytocin, estrogen and progestin receptors in the bovine endometrium during the estrous cycle

1988 ◽  
Vol 118 (1) ◽  
pp. 96-104 ◽  
Author(s):  
H. H. D. Meyer ◽  
Th. Mittermeier ◽  
D. Schams
Keyword(s):  
Estrous Cycle ◽  
Luteal Phase ◽  
Oxytocin Receptor ◽  
Minor Importance ◽  
Progestin Receptors ◽  
Progestin Receptor ◽  
Nuclear Estrogen Receptor ◽  
Low Sensitivity ◽  
A Minor ◽  
Estradiol Levels

Abstract. The levels of oxytocin receptor (OTR), cytosolic progestin receptor (cPR), cytosolic and nuclear estrogen receptor (cER, nER) were measured in the endometrium of 28 heifers that had been slaughtered on a defined day of the estrous cycle, In an additional, trial endometrial tissue obtained from 78 heifers or cows at the abattoir was analyed for OTR. OTR was absent during the luteal phase (after day 6), but a minor elevation was observed after day 15. OTR increased rapidly after luteolysis on days 17–18 reaching a maximum during estrous on day 21, and decreased again during days 1–6. cER and cPR were different to OTR but followed a similar pattern with maximal levels during days 1–8 of the estrous cycle. At day 12 both receptors were minimal and increased again towards day 21. nER was maximal at day 19–21 coinciding with maximal estradiol levels and estrous. Our data indicate that owing to an increasing sensitivity of the endometrium to progesterone and estradiol after day 12, these steroids may be mainly responsible for the initiation of first PGF2α surges and luteolysis. Oxytocin seems to be of minor importance at this stage owing to low sensitivity of the endometrium for oxytocin.

scholarly journals Contractile and Endothelium-Dependent Dilatory Responses of Cerebral Arteries at Various Extracellular Magnesium Concentrations

1991 ◽  
Vol 11 (1) ◽  
pp. 161-164 ◽  
Author(s):  
Mária Faragó ◽  
Csaba Szabó ◽  
Eörs Dóra ◽  
Ildikó Horváth ◽  
Arisztid G. B. Kovách
Keyword(s):  
Smooth Muscle ◽  
Vascular Reactivity ◽  
Calcium Influx ◽  
Cerebral Arteries ◽  
Inhibitory Effect ◽  
Contractile Responses ◽  
Middle Cerebral Arteries ◽  
The Right ◽  
Endothelial Receptor

To clarify the effect of extracellular magnesium (Mg2+) on the vascular reactivity of feline isolated middle cerebral arteries, the effects of slight alterations in the Mg2+ concentration on the contractile and endothelium-dependent dilatory responses were investigated in vitro. The contractions, induced by 10−8-10−5 M norepinephrine, were significantly potentiated at low Mg2+ (0.8 m M v. the normal, 1.2 m M). High (1.6 and 2.0 m M) Mg2+ exhibited an inhibitory effect on the contractile responses. No significant changes, however, in the EC50 values for norepinephrine were found. The endothelium-dependent relaxations induced by 108–10−5 M acetylcholine were inhibited by high (1.6 and 2.0 m M) Mg2+. Lowering of the Mg2+ concentration to 0.8 m M or total withdrawal of this ion from the medium failed to alter the dilatory potency of acetylcholine. The changes in the dilatory responses also shifted the EC50 values for acetylcholine to the right. The present results show that the contractile responses of the cerebral arteries are extremely susceptible to the changes of Mg2+ concentrations. In response to contractile and endothelium-dependent dilatory agonists, Mg2+ probably affects both the calcium influx into the endothelial and smooth muscle cells as well as the binding of acetylcholine to its endothelial receptor. Since Mg2+ deficiency might facilitate the contractile but not the endothelium-dependent relaxant responses, the present study supports a role for Mg2+ deficiency in the development of the cerebral vasospasm.

Cerebrovascular characterization of clazosentan, the first nonpeptide endothelin receptor antagonist clinically effective for the treatment of cerebral vasospasm. Part I: Inhibitory effect on endothelinA receptor—mediated contraction

2005 ◽  
Vol 102 (6) ◽  
pp. 1101-1107 ◽  
Author(s):  
Hartmut Vatter ◽  
Michael Zimmermann ◽  
Veronika Tesanovic ◽  
Andreas Raabe ◽  
Lothar Schilling ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Cerebral Vasospasm ◽  
Isometric Force ◽  
Inhibitory Effect ◽  
Affinity Constant ◽  
Dependent Manner ◽  
Content Type ◽  
The Right ◽  
Fine Print

Object. The central role of endothelin (ET)—1 in the development of cerebral vasospasm after subarachnoid hemorrhage is indicated by the successful treatment of this vasospasm in several animal models by using selective ETA receptor antagonists. Clazosentan is a selective ETA receptor antagonist that provides for the first time clinical proof that ET-1 is involved in the pathogenesis of cerebral vasospasm. The aim of the present investigation was, therefore, to define the pharmacological properties of clazosentan that affect ETA receptor—mediated contraction in the cerebrovasculature. Methods. Isometric force measurements were performed in rat basilar artery (BA) ring segments with (E+) and without (E−) endothelial function. Concentration effect curves (CECs) were constructed by cumulative application of ET-1 or big ET-1 in the absence or presence of clazosentan (10−9, 10−8, and 10−7 M). The inhibitory potency of clazosentan was determined by the value of the affinity constant (pA2). The CECs for contraction induced by ET-1 and big ET-1 were shifted to the right in the presence of clazosentan in a parallel dose-dependent manner, which indicates competitive antagonism. The pA2 values for ET-1 were 7.8 (E+) and 8.6 (E−) and the corresponding values for big ET-1 were 8.6 (E+) and 8.3 (E−). Conclusions. The present data characterize clazosentan as a potent competitive antagonist of ETA receptor—mediated constriction of the cerebrovasculature by ET-1 and its precursor big ET-1. These functional data may also be used to define an in vitro profile of an ET receptor antagonist with a high probability of clinical efficacy.

scholarly journals Ventilation/perfusion mismatch during lung aeration at birth

2014 ◽  
Vol 117 (5) ◽  
pp. 535-543 ◽  
Author(s):  
Justin A. R. Lang ◽  
James T. Pearson ◽  
Arjan B. te Pas ◽  
Megan J. Wallace ◽  
Melissa L. Siew ◽  
...  
Keyword(s):  
Pulmonary Arteries ◽  
Left Lung ◽  
X Ray ◽  
Lung Aeration ◽  
X Ray Imaging ◽  
Iodine Level ◽  
Pulmonary Shunting ◽  
Left And Right ◽  
Near Term ◽  
The Right

At birth, the transition to newborn life is triggered by lung aeration, which stimulates a large increase in pulmonary blood flow (PBF). Current theories predict that the increase in PBF is spatially related to ventilated lung regions as they aerate after birth. Using simultaneous phase-contrast X-ray imaging and angiography we investigated the spatial relationships between lung aeration and the increase in PBF after birth. Six near-term (30-day gestation) rabbits were delivered by caesarean section, intubated and an intravenous catheter inserted, before they were positioned for X-ray imaging. During imaging, iodine was injected before ventilation onset, after ventilation of the right lung only, and after ventilation of both lungs. Unilateral ventilation increased iodine levels entering both left and right pulmonary arteries (PAs) and significantly increased heart rate, iodine ejection per beat, diameters of both left and right PAs, and number of visible vessels in both lungs. Within the 6th intercostal space, the mean gray level (relative measure of iodine level) increased from 68.3 ± 11.6 and 70.3 ± 7.5%·s to 136.3 ± 22.6 and 136.3 ± 23.7%·s in the left and right PAs, respectively. No differences were observed between vessels in the left and right lungs, despite the left lung not initially being ventilated. The increase in PBF at birth is not spatially related to lung aeration allowing a large ventilation/perfusion mismatch, or pulmonary shunting, to occur in the partially aerated lung at birth.

scholarly journals Cyclic GMP regulates activation of phosphoinositidase C by bradykinin in sensory neurons

1996 ◽  
Vol 316 (2) ◽  
pp. 539-544 ◽  
Author(s):  
Justine S. HARVEY ◽  
Gillian M. BURGESS
Keyword(s):  
Cyclic Gmp ◽  
Inhibitory Effect ◽  
Neonatal Rat ◽  
Drg Neurons ◽  
Rapid Phase ◽  
Surface Receptors ◽  
Similar Inhibitory Effect ◽  
Key Factor ◽  
The Right ◽  
Oxide Synthase

Prior exposure of cultured neonatal rat dorsal root ganglion (DRG) neurons to bradykinin resulted in marked attenuation of bradykinin-induced activation of phosphoinositidase C (PIC). The (logconcentration)–response curve for bradykinin-induced [3H]inositol trisphosphate ([3H]IP3) formation was shifted to the right and the maximum response was reduced. Bradykinin increases cyclic GMP (cGMP) in DRG neurons [Burgess, Mullaney, McNeill, Coote, Minhas and Wood (1989) J. Neurochem. 53, 1212–1218] and treatment of the neurons with dibutyryl cGMP (dbcGMP) had a similar, inhibitory, effect on bradykinin-induced [3H]IP3 formation. NG-Nitro-L-arginine (LNNA) blocked bradykinin-induced formation of cGMP. It prevented the functional uncoupling induced by pretreatment with bradykinin, but not the inhibitory effect of dbcGMP on [3H]IP3 formation. The ability of LNNA to prevent desensitization was reversed by excess L-arginine, indicating that its actions were mediated through inhibition of nitric oxide synthase. In addition to functional desensitization, exposure to bradykinin reduced the number of cell-surface receptors detected with [3H]bradykinin, without affecting its KD value for the remaining sites. In contrast to bradykinin, pretreatment with dbcGMP had no effect on either the KD or Bmax for [3H]bradykinin binding. This implies that the inhibitory effect of dbcGMP was downstream from the binding of bradykinin to its receptor and upstream of IP3 formation. The lack of effect of dbcGMP on [3H]bradykinin binding suggests that the decrease in receptor number induced by bradykinin was mediated by a different mechanism and was not a key factor in the rapid phase of desensitization in these cells.

Regulation of Oxytocin Receptors and Oxytocin Receptor Signaling

2007 ◽  
Vol 25 (1) ◽  
pp. 052-059 ◽  
Author(s):  
Andrew Blanks ◽  
Anatoly Shmygol ◽  
Steven Thornton
Keyword(s):  
Oxytocin Receptor ◽  
Receptor Signaling ◽  
Oxytocin Receptors

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

Localization of oxytocin receptor mRNA in the ovine uterus during the oestrous cycle and early pregnancy

1994 ◽  
Vol 12 (1) ◽  
pp. 93-105 ◽  
Author(s):  
K R Stevenson ◽  
P R Riley ◽  
H J Stewart ◽  
A P F Flint ◽  
D C Wathes
Keyword(s):  
Mrna Expression ◽  
Optical Density ◽  
Receptor Gene ◽  
Oxytocin Receptor ◽  
Oestrous Cycle ◽  
Luminal Epithelium ◽  
Binding Studies ◽  
Receptor Mrna ◽  
Oxytocin Receptors ◽  
Ovine Uterus

ABSTRACT A synthetic 45-mer oligonucleotide corresponding to part of the ovine endometrial oxytocin receptor cDNA was hybridized to sections of ovine uterus collected from 40 ewes at different stages during the oestrous cycle, the first 3 weeks of pregnancy and seasonal anoestrus. The quantity of oxytocin receptor mRNA was measured as the optical density (OD) value on autoradiographs using image analysis. Message first appeared in the luminal epithelium on days 14–15 of the cycle, increasing to a peak OD of 0·48 at oestrus and decreasing again between days 2 and 5. Oxytocin receptor mRNA in the superficial glands, deep glands and caruncular stroma increased between day 15 and oestrus to peak OD values of 0·17, 0·11 and 0·11 respectively, declining again by day 2 and reaching basal values (OD<0·015) by day 5. Hybridization to the myometrium tended to rise from a mean OD value of 0·01 on days 2–15 to a peak of 0·03±0·01 (mean±s.e.m.) on days 0–1, but the change was not significant. In pregnant ewes there was no detectable oxytocin receptor mRNA on days 14–15 in any region, but hybridization to the luminal epithelium was present in two of three ewes on day 21. In anoestrous ewes oxytocin receptor mRNA concentrations in all areas of the endometrium were approximately half those measured at oestrus. Optical density readings for oxytocin receptor mRNA in the various uterine compartments were compared with measurements of oxytocin receptors in the same regions as assessed by binding studies using the 125I-labelled oxytocin antagonist d(CH2)5[Tyr(Me)2,Thr4,Tyr-NH29]-vasotocin (125I-labelled OTA). In the endometrium, receptor mRNA and 125I-labelled OTA binding patterns changed in parallel, and both sets of measurements were significantly correlated (P<0·01). In the myometrium, a significant increase in 125I-labelled OTA binding occurred at oestrus; this was not accompanied by a similar increase in oxytocin receptor mRNA hybridization. This study helps to confirm that the previously identified cDNA clone is derived from the ovine oxytocin receptor, as patterns of oxytocin receptor mRNA expression in the endometrium closely resembled those of oxytocin binding. Maximum expression and binding both occurred at oestrus, suggesting that regulation of the oxytocin receptor gene in the uterus occurs principally at the transcriptional, rather than at the translational, level. Failure to detect a significant increase in myometrial mRNA expression at oestrus may indicate that the endometrial and myometrial oxytocin receptors are of different isoforms.

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