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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Virgin female Wistar rats were ovariectomized and 2 days later were given a single .2 ml dose of steroid im. Medroxyprogesterone acetate, 100 mg/kg of body weight or estradiol valerate 100 mcg were used. Group 1 (controls) received only solvents, Group 2 received progestogen in saline, Group 3 received the estrogen in oil, and Group 4 received both steroids. On selected days after treatment a rat from each group was killed, the uterus removed, and 2 myometrial strips were suspended in isolated organ baths on Statha G10B strain gauges for isometric recording. After 30 minutes, a dose of either 10 mcg/ml of acetylcholine or .25 mcg/ml of oxytocin was added to each bath. Tension was recorded for 10 minutes followed by a 15-minute wash. These doses were supramaximal. Responses began with a brief contraction and then became a series of fast powerful contrations which continued for 30-60 minutes. Each strip was later removed, prepared for sectioning, and length and cross-section were measured. Controls responded similarly to saline and to oil injections. There was a significnt initial increase in the response to both acetylcholine (p less than .05) and oxytocin (p less than .01). From Days 6 to 20 the responses did not change significantly. After Day 20 the response to acetylcholine declined significantly (p less than .01) but the response to oxytocin was unchanged for the 60 days of the test. With estrogen treatment, increase in response to both spasmogens was highly significant (p less than .001) in the first 18 days at which time it reached a plateau and remained the same for 60 days. With the progestogen treatment the mean response to acetylcholine increased significantly for the first 2 days (p less than .01) then maintained a plateau for the next 3 days equal to the control group and subsequently declined slowly (p less than .001). The contractile response to oxytocin remained constant for 60 days. With estrogen plus progestogen treatment there was a significant increase in contractility up to Day 5 (p less than .001). From Days 5 to 9 plateau levels were maintained with acetycholine and at a lower level with oxytocin. After Day 9 there was a significant decline in both spasmogens effect (p less than .001). With controls and all steroid treatments there was a highly significant difference in responses to acetylcholine and to oxytocin, with acetylcholine consistently giving stronger responses (p less than .001) than oxytocin. Results indicated that medroxyprogesterone acetate required the presence of estrogen for its myometrial action. There was also evidence that estrogen actions were modified by progestogen. It is concluded that single doses of estrogen and progestogen had depot actions of adequate intensity and duration for prolonged studies in myometrial contractility and that there was significant interaction between them when given together. Rat myometrium retained a significant response to spasmogens for at least 60 days after ovariectomy without steroid replacement, perhaps from adrenocortical steroid secretion.
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PMID:Sustained effects on synthetic ovarian steroids of rat myometrial contractility. 96 82

Intact cyclic ewes have been used in experiments designed to examine the mechanism by which uterine oxytocin receptor synthesis is controlled during the oestrous cyclic. Previous experiments have shown that the prostaglandin F2 alpha analogue cloprostenol is luteolytic in ewes receiving oxytocin by continuous intra-venous infusion. When ewes receiving oxytocin are given cloprostenol uterine oxytocin receptor concentrations are raised, whereas in animals receiving oxytocin alone, they remain low. To investigate whether inhibition of oxytocin receptor binding activity by oxytocin is either dependent on elevated plasma progesterone concentrations or over-ridden by oestrogens secreted by ovarian follicles maturing as a result of cloprostenol treatment, ewes were given oxytocin by continuous intravenous infusion (3 nmol h-1) between Days 12 and 17 after oestrus and one of the following: no further treatment; cloprostenol [125 micrograms intramuscularly (i.m.)] on Day 15; progesterone, by subcutaneous implant, from Day 14 with cloprostenol on Day 15; medroxyprogesterone acetate (MPA; 6 mg depot i.m.) on Day 14 followed by cloprostenol on Day 15; or oestradiol-17 beta (2.75 mumol i.m.) on Days 14 and 15. Concentrations of oxytocin receptor were measured at autopsy on Day 17 in caruncular endometrium, intercaruncular endometrium and myometrium. Ovarian follicles and corpora lutea were examined to determine the effect of treatment on these tissues. Treatment with oxytocin alone resulted in the maintenance of corpora lutea, reduced follicular development and a low concentration of uterine oxytocin receptor. Cloprostenol initiated luteolysis in oxytocin-treated ewes. This was associated with a high level of oxytocin receptor binding activity in all ewes except those receiving exogenous progesterone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of continuous infusion of oxytocin on ovarian function and uterine oxytocin receptor concentration in the cyclic ewe. 133 7

A 1968 Indian study compared the effect of Norlutin (17-alpha ethynl 19-nor testosterone) and Provera (6-methyl acetoxyprogesterone) suspensions on the uterine motility of virgin rats and mice to the action of natural progesterone and testosterone. The test animals were spayed and 2 weeks later, the rats were injected with 2 mcg of estradiol benzoate daily for 3 consecutive days. The mice received .2 mcg injections. On day 4 the animals were sacrificed and the uterine horns were suspended in a 40 ml organ bath containing Tyrode solution at 32 degrees centigrade and aerated with 5% carbon dioxide in oxygen. Rat uterine movement was recorded isotonically with a linear frontal writing lever while a heart lever was used for mice. The action of the compounds was also tested on oxytocin-induced spasms. Norlutin suspension (1.25-50 mcg/ml) inhibited both amplitude and tone of uterine contraction within 2-10 minutes and lasted more than 1 hour. The uterus failed to respond to oxytocin during peak Norlutin action. A progesterone concentration of 1.25 mcg also produced uterine relaxation but its effect on contractual tone was insignificant. Graded concentrations of Provera and testosterone suspension failed to effect uterine motility in rats and mice.
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PMID:Effect of some synthetic progestational steroids on uterine contractions. 578 55

Both the fertility inhibiting effects of breastfeeding and the lactation inhibiting effects of hormonal contraceptives should be considered in developing postpartum family planning programs for lactating women. Because a high percentage of female contraceptive acceptors discontinue use within a year, the largest birth intervals may be achieved by delaying the initiation of contraception to take advantage of lactational infertility in the first postpartum months. Although evaluation of existing data on the effects of oral contraceptives on lactation is difficult, findings suggest that low-dose progestins may have a less detrimental effect on lactation than combined oral contraceptives. Depo-provera appears to enhance milk volume and duration of lactation, but the unknown side effects of transmission of steroids to the infant and changes in milk composition suggest caution in recommending it for nursing mothers. Results of research on possible effects of IUDs on lactation are conflicting and difficult to interpret, but possible mechanisms through prolactin secretion or oxytocin have been suggested for such an effect. Numerous methodological problems hamper efforts to evaluate evidence of the relationship of contraception to lactation to provide recommendations for family planning programs. The most prudent course where possible is to avoid giving hormonal contraceptives to the lactating woman. Where only hormonal contraceptives are acceptable, the best approach is probably to delay their use for at least 3 months postpartum to allow lactation to become established and the infant to mature.
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PMID:Contraceptive choices for lactating women: suggestions for postpartum family planning. 621 32

Fertilized eggs from rabbits 1 or 2.5 days after insemination were transferred to the oviduct or uterine horn of recipients that had received a single subcutaneous injection of 20 or 30 mg of one of seven long-acting progestins. The rabbits were observed daily, and the number of implantation sites was determined 10 or 11 days after egg transfer. No implantation sites were recorded in the recipient does treated with progesterone or ZK-5623 (Schering AG, Berlin, West Germany), a nor-steroid compound. Thirty-nine percent and 51% of the transferred eggs implanted in the recipient does treated with ZK-5410 (Schering AG) and chloromadinone acetate (Eli Lilly & Company, Indianapolis, IN), respectively. However, most of the pregnant animals aborted 14 to 20 days after egg transfer. The pregnancy was either maintained to term or was prolonged beyond the normal gestation length in the does treated with other compounds, ZK-53915, ZK-9349 (Schering AG) or Depo-Provera (Upjohn Company, Kalamazoo, MI). The young delivered after a subcutaneous injection of 17 beta-estradiol and oxytocin were found normal and active.
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PMID:Maintenance of pregnancy in rabbits treated with long-lasting progestins. 685 82

We tested the hypothesis that oxytocin (Oxt) acts in the lumbar spinal cord to attenuate reflex pressor (mean arterial pressure, MAP) and heart rate (HR) responses to static hindlimb contraction (i.e., the exercise pressor reflex). Thus we compared MAP and HR responses to electrically stimulated hindlimb static contraction in the anesthetized cat before and after intrathecal injection of Oxt (30 pmol, n = 3; 300 pmol, n = 6; or 3 nmol, n = 6). The 300-pmol dose was most effective; it attenuated the pressor response to static contraction by 39 +/- 10% but had no effect on HR. In three other cats, contraction-induced increases in MAP and HR were monitored before and after intrathecal injection of 300 pmol of Oxt + 300 nmol of the selective Oxt receptor antagonist [d(CH2)5(1),O-Me-Tyr2,Thr4,Tyr9,Orn8]vasotocin. Pretreatment with the antagonist eliminated the effect of Oxt on MAP. In an additional 10 cats, increases in these same variables in response to static contraction were compared before and after intrathecal injection of the Oxt antagonist (30 nmol, n = 3 or 300 nmol, n = 7) into the lumbar spinal cord (L1-L7). Whereas 30 nmol of the Oxt antagonist had no effect, the 300-nmol dose augmented the contraction-induced pressor and HR responses by 28 +/- 7 and 32 +/- 17%, respectively. These data imply that endogenous Oxt modulates the exercise pressor reflex by its action on Oxt receptors in the lumbar spinal cord that can attenuate sensory nerve transmission from skeletal muscle.
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PMID:The exercise pressor reflex is attenuated by intrathecal oxytocin. 794 31

Endothelins (ETs) were initially thought to be primarily involved in the control of cardiovascular activity, but the presence of ETs and their receptors in a wide variety of other tissues has suggested a much broader range of functions. Specific receptors for ETs are found in nonvascular tissues including neuronal, neuroendocrine, and endocrine cells. In addition, immunoreactive ETs are present in the brain, pituitary, and peripheral endocrine tissues. However, the ET levels in hypothalamo-hypophysial portal and peripheral blood are low, suggesting that the ET system participates in neuroendocrine regulation through paracrine and/or autocrine mechanisms. Both ETA and ETB receptors are expressed in the hypothalamus, adrenal, parathyroid glands, pancreas, ovary, uterus, placenta, and prostate, while only ETA receptors are expressed in GT1 neurons, anterior pituitary cells, alpha T3-1 immortalized gonadotropes, parathyroid-derived cells, thyrocytes, testicular Leydig and Sertoli cells, normal and neoplastic ovarian granulosa cells, chondrocytes, and other cell types. Activation of ET receptors elicits the sequence of cellular events typical of Ca(2+)-mobilizing receptors, with prominent increases in phosphoinositide hydrolysis and elevations of [Ca2+]i that occur in oscillatory and nonoscillatory modes depending on the cell type. ET-induced activation of the phosphoinositide/Ca(2+)- mobilizing pathway in neuronal and endocrine cells is associated with rapid stimulation of secretory responses, including release of gonadotropin-releasing hormone, oxytocin, vasopressin, substance P, atrial natriuretic peptides, gonadotropins, thyrotropin, growth hormone, parathyroid hormone, aldosterone, and catecholamines. On the other hand, ET has inhibitory actions on prolactin, progesterone, and renin release. In addition to stimulating phospholipase C-dependent pathways, ETs also activate phospholipase D-and MAP-kinase-dependent pathways in some of their target cells, as well as expression of early response genes and increased mitogenic activity. In many neuroendocrine cells, ET induces rapid and marked desensitization of its signaling system, in association with extensive internalization of ET receptors and reduced signaling and secretory responses. These findings raise the possibility that ETs participate in the control of secretory responses in the hypothalamo-pituitary system and peripheral endocrine cells, as well as in long-term aspects of regulation in certain neuroendocrine cells.
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PMID:Expression and signal transduction pathways of endothelin receptors in neuroendocrine cells. 881 99

Estrogen receptor alpha (ERalpha) and estrogen receptor beta (ERbeta) are differentially distributed in the brain and likely mediate different estrogen-dependent processes. ERbeta is abundant in the bed nucleus of the stria terminalis, medial preoptic nucleus, paraventricular nucleus of the hypothalamus and the amygdala of the rat. In the paraventricular nucleus, which is devoid of ERalpha, ERbeta is colocalized with the neuropeptides, oxytocin and vasopressin, suggesting a potential functional role for ERbeta in the regulation of these peptides. We examined the regulation of ERbeta mRNA expression in the rat brain by 17beta-estradiol and the phytoestrogen, coumestrol. 17beta-Estradiol treatment decreased ERbeta mRNA in situ hybridization signal by 44.5% in the paraventricular nucleus of the hypothalamus (PVN), but had no effect in the bed nucleus of the stria terminalis (BnST) or the medial preoptic nucleus (MPA). In contrast, dietary exposure to coumestrol increased ERbeta mRNA signal by 47.5% in the PVN but had no effect in the BnST or the MPA. These data demonstrate that like ERalpha, ERbeta is down regulated by estrogen in a region specific manner in the rat brain. Furthermore, exposure to coumestrol may modulate ERbeta-dependent processes by acting as an anti-estrogen at ERbeta. This data contradicts results from cell transfection assays which suggest an estrogenic activity of coumestrol on ERbeta, indicating that the mode of action may be tissue specific, or that metabolism of dietary coumestrol may alter its effects. Because the highest concentrations of phytoestrogens are found in legumes, vegetables and grains, they are most prevalent in vegetarian and traditional Asian diets. Understanding the neuroendocrine effects of phytoestrogens is particularly important now that they are being marketed as a natural alternative to estrogen replacement therapy and sold in highly concentrated pills and powders.
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PMID:Regulation of estrogen receptor beta mRNA in the brain: opposite effects of 17beta-estradiol and the phytoestrogen, coumestrol. 1010 Dec 43

Oxytocin is synthesized by magnocellular neurons in the supraoptic and paraventricular nuclei (SON and PVN) and during pregnancy progesterone prevents premature activation of oxytocin neurons. Progesterone receptors (PR) are not detectable in SON oxytocin neurons of non-pregnant rats, so we sought to determine whether they are expressed during pregnancy and parturition. In addition, we examined PR expression in brainstem and hypothalamic regions that have known direct projections to the SON. Neuronal immunoreactive PR (irPR)-labeled nuclei were counted in sections from proestrous virgin, late pregnant (day 21) and parturient rats (90 min from birth onset). IrPR nuclei were not evident in the SON at any stage but irPR expression in the medial preoptic nucleus (MPA) significantly increased in pregnancy and parturition (159% and 189% of proestrous controls, respectively). Other hypothalamic areas did not exhibit a significant change in irPR expression. In the nucleus tractus solitarius (NTS) in the brainstem, there was no significant change in irPR in late pregnancy, but there was a significant reduction in irPR expression at parturition (22% of proestrous controls). Very few NTS neurons immunoreactive for tyrosine hydroxylase (irTH), and thus putatively noradrenergic, contained irPR. These findings taken with evidence that brainstem irTH neurons projecting to the SON are stimulated at parturition, whereas MPA cells projecting to the SON are not, suggest that any direct actions of progesterone or progesterone withdrawal on NTS or SON neurons are not mediated through the classical PR. Upregulation of PR expression in the MPA during pregnancy and parturition may relate to the onset of maternal behavior and/or regulation of GnRH neuronal activity.
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PMID:Progesterone receptor expression in the pregnant and parturient rat hypothalamus and brainstem. 1181 28

MAP (mitogen-activated protein) kinase (also called Erk 1/2) plays a crucial role in cell proliferation and differentiation. Its impact on secretory events is less well established. The interplay of protein kinase C (PKC), PI3-kinase and cellular tyrosine kinase with MAP kinase activity using inhibitors and compounds such as glucose, phorbol 12-myristate 13-acetate (PMA) and agonists of G-protein coupled receptors like gastrin releasing peptide (GRP), oxytocin (OT) and glucose-dependent insulinotropic peptide (GIP) was investigated in INS-1 cells, an insulin secreting cell line. MAP kinase activity was determined by using a peptide derived from the EGF receptor as a MAP kinase substrate and [32P]ATP. Glucose as well as GRP, OT and GIP exhibited a time-dependent increase in MAP kinase activity with a maximum at time point 2.5 min. All further experiments were performed using 2.5 min incubations. The flavone PD 098059 is known to bind to the inactive forms of MEK1 (MAPK/ERK-Kinase) thus preventing activation by upstream activators. 20 microM PD 098059 (IC50 = 5 microM) inhibited MAP kinase stimulated by either glucose, GRP, OT, GIP or PMA. Inhibiton ("downregulation") of PKC by a long term (22 h) pretreatment with 1 microM PMA did not influence MAP kinase activity when augmented by either of the above mentioned compound. To investigate whether PI3-kinase and cellular tyrosine kinase are involved in G-protein mediated effects on MAP kinase, inhibitors were used: 100 nM wortmannin (PI3-kinase inhibitor) reduced the effects of GRP, OT and GIP but not that of PMA; 100 microM genistein (tyrosine kinase inhibitor) inhibited the stimulatory effect of either above mentioned compound on MAP kinase activation. Inhibition of MAP kinase by 20 microM PD 098059 did not influence insulin secretion modulated by either compound (glucose, GRP, OT or GIP). [3H]Thymidine incorporation, however, was severely inhibited by PD 098059. Thus MAP kinase is important for INS-1 cell proliferation but not for its insulin secretory response with respect to major initiators and modulators of insulin release. The data indicate that MAP kinase is active and under the control of MAP kinase. PKC is upstream of a genistein-sensitive tyrosine kinase and probably downstream of a PI3-kinase in INS-1 cells.
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PMID:Role of protein kinase C, PI3-kinase and tyrosine kinase in activation of MAP kinase by glucose and agonists of G-protein coupled receptors in INS-1 cells. 1236 12


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