Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

(1) Oxytocin is synthesized in the luteal cells of all species so far studied, including the human. Vasopressin is also synthesized, but at a much lower rate. (2) The oxytocin-neurophysin gene is expressed in granulosa cells and granulosa-derived luteal cells but not in theca cells. Ovulation or spontaneous luteinization initiates the gene expression which peaks in the early luteal phase and ceases around mid-cycle. (3) Luteal oxytocin concentrations rise with considerable delay after the peak of specific mRNA and reach maximal levels around mid-cycle. Oxytocin concentrations fall to low levels in the late luteal phase and in pregnancy. (4) Thecal tissue produces substances such as catecholamines and ascorbic acid that stimulate oxytocin secretion in granulosa cells. The adrenergic innervation of thecal tissue provides a source of catecholamines and may therefore serve a modulatory function in ovarian oxytocin secretion. (5) Oxytocin has little or no direct effect on luteal progesterone production. (6) Oxytocin inhibits LH-stimulated prostacyclin production in luteal cells of cows. Oxytocin may induce the release of PGF-2 alpha or lipo-oxygenase products from the ovary but this has not yet been documented. (7) PGF-2 alpha releases oxytocin from the ovary but does not turn off its synthesis. (8) The concept that ovarian oxytocin participates in the luteolytic process is gaining acceptance. In some species (sheep, goat) ovarian oxytocin acts as a hormone causing PGF-2 alpha release from the uterus. In others it acts in a paracrine or autocrine fashion on ovarian prostanoid production (cow, possibly primates).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Oxytocin and ovarian function. 305 1

We have investigated the ability of three synthetic prostanoids to directly influence uterine contractility by studying the effects in vitro. Strips of lower uterine segment smooth muscle were obtained from women undergoing elective cesarean section at term. The ability of these strips to develop tension in the presence of cumulative additions of prostanoids or oxytocin was assessed. Spontaneous contractions were inhibited by ZK 96.480, a stable synthetic analog of prostaglandin I2, with a 50th percentile effective concentration (EC50) of 8 nmol/L. Both sulprostone, an analog with selectivity for some of the actions of prostaglandin E2, and U-44069, a stable thromboxane A2 mimetic, caused excitation with EC50s of 20 and 16 nmol/L, respectively. The EC50 for oxytocin was 6 nmol/L. There were no significant differences in the maximal tensions developed in response to the excitatory prostanoids or oxytocin.
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PMID:The effects of some synthetic prostanoids on the contractility of the human lower uterine segment in vitro. 327 28

Normal corpus luteum function is determined by function in the follicular as well as the luteal phase. In the follicular phase adequate follicle-stimulating hormone (FSH) and oestrogen stimulation are required for granulosa cell mitosis and luteinizing hormone (LH) receptor synthesis. An increase in LH pulse frequency may also be necessary for adequate oestrogen synthesis and preparation of follicular cells for luteinization and secretion of progesterone. The nature of LH release may also influence luteal function and pre-ovulatory progesterone may increase the responsiveness of the follicle to gonadotrophins. The thecal vascular network becomes extensive around pre-ovulatory follicles and may influence access of gonadotrophins and/or the ability of follicular cells to respond to them. Further vascularization is an early feature of luteinization. Angiogenic factors are found in luteal tissue and prostacyclin increases luteal blood flow. The corpus luteum consists of large cells which secrete most of the progesterone and have prostaglandin F2 alpha receptors and small cells which are responsive to LH. In the luteal phase subnormal luteal function has not been associated with a reduction in LH concentration, pulse frequency or amplitude. The number and occupancy of LH receptors and adenylate cyclase activity do not appear to be altered by a reduction in luteal function. Low density lipoprotein provides the substrate and somatomedin C modulates among other hormones' influences, progesterone production. In addition to the cAMP second messenger system phosphatidyl inositol metabolism may also be associated with LH stimulation. Luteolysis is an active process; prostaglandin F2 alpha or lipoxygenase products and possibly an endogenous GnRH-like ovarian hormone may mediate it as also may oxytocin in some species.
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PMID:The corpus luteum. 328 62

The changes of concentrations of prostaglandins (PG) are cyclic in the uterine tissues and related to steroid ovarian hormones. The role in normal menstruation is presumably related to a local haemodynamic effect. PGF2 alpha vasoconstricts the endometrial vessels during menstruation and contracts the smooth muscle of the myometrium. PGE2 vasodilates the vessels of the endometrium, and PGI2 relaxes smooth muscle, vasodilates the vessels of the myometrium and inhibits thrombocyte aggregation. The pathological conditions dysmenorrhea and menorrhagia relates to symptoms which seem to be exaggerations of normal activities, probably due to increased PG levels. Prostaglandin synthesis inhibitors (PGSI) in women have not been able to prevent ovulation, but animal experiments have shown that the bursting of the follicle demands prostaglandins. In vitro experiments with human tissue have shown that PG is necessary for the occurrence of dissociation of connective tissue around the apex. Luteolysis is due to PG in several species, but it has not been possible to find this direct effect of PG upon luteolysis in women. However, there are indications that the PG functions as a mediator for or is mediated by catecholamines and/or oxytocin.
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PMID:Prostaglandins in the menstrual cycle of women. A review. 329 13

Evidence was cited to show that: (1) prostacyclin (PGI2) plays a luteotrophic role in the bovine corpus luteum and that products of the lipoxygenase pathway of arachidonic acid metabolism, especially 5-hydroxyeicosatetraenoic acid play luteolytic roles; (2) oxytocin of luteal cell origin plays a role in development, and possibly in regression, of the bovine corpus luteum; and (3) luteal cells arise from two sources; the characteristic small luteal cells at all stages of the oestrous cycle and pregnancy are of theca cell origin; the large cells are of granulosa cell origin early in the cycle, but a population of theca-derived large cells appears later in the cycle. Results of in vitro studies with total dispersed cells and essentially pure preparations of large and small luteal cells indicate that: (1) the recently described Ca2+-polyphosphoinositol-protein kinase C second messenger system is involved in progesterone synthesis in the bovine corpus luteum; (2) activation of protein kinase C is stimulatory to progesterone synthesis in the small luteal cells; (3) activation of protein kinase C has no effect on progesterone synthesis in the large luteal cells; and (4) protein kinase C exerts its luteotrophic effect in total cell preparations, in part at least, by stimulating the production of prostacyclin. The protein kinase C system may cause down regulation of LH receptors in the large cells.
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PMID:Control of steroidogenesis in small and large bovine luteal cells. 332 92

The effects of oestradiol, oxytocin, progesterone and hydrocortisone in vitro on prostaglandin (PG) output from guinea-pig endometrium, removed on days 7 and 15 of the oestrous cycle and maintained in tissue culture for 3 days, have been investigated. Oestradiol (3.7 to 3700 nM) and oxytocin (2 to 200 pM) did not stimulate endometrial PGF2 alpha output, thus not confirming the findings of a previous report (Leaver & Seawright, 1982), nor did they stimulate the outputs of PGE2 and 6-keto-PGF1 alpha. In fact, oestradiol (3700 nM) inhibited the outputs of PGF2 alpha, PGE2 and, to a lesser extent, 6-keto-PGF1 alpha. Progesterone (3.2 to 3200 nM) inhibited the outputs of PGF2 alpha and PGE2; hydrocortisone (2.8 to 2800 nM) had no effect on endometrial PG output. These findings indicate that the inhibitory effect of progesterone on endometrial PG synthesis and release in the guinea-pig is not due to progesterone having a glucocorticoid-like action. Furthermore, progesterone had no effect on 6-keto-PGF1 alpha output, suggesting that the mechanisms controlling endometrial PGI2 synthesis (as reflected by measuring 6-keto-PGF1 alpha) are different from those controlling endometrial PGF2 alpha and PGE2 synthesis.
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PMID:Effects of oestradiol, progesterone, hydrocortisone and oxytocin on prostaglandin output from the guinea-pig endometrium maintained in tissue culture. 343 57

The in vitro spontaneous isometric-developed tension (IDT) of uterine horns obtained from diestrous rats exhibited, after 60 min of post-isolation activity, a clear decrease in magnitude, averaging 18.2 +/- 5.2%. In presence of tolbutamide, a concentration-dependent decrease of IDT, significantly greater than the spontaneous reduction (75.1 +/- 5.4%, with tolbutamide at 10(-4) M), was observed. Incubation with propranolol (10(-6) M) or with sotalol (10(-4) M) failed to alter the negative inotropism evoked by tolbutamide. On the other hand, the sulfonylurea (10(-4) M) shifted most points of the dose-response curve to the right for the contractile stimulation elicited by oxytocin, an influence not altered by the simultaneous presence of propranolol or sotalol. Tolbutamide failed to influence the negative inotropic dose-response curve for isoproterenol and did not modify the decrease in contractions evoked by theophylline (10(-4) M). It was also found that tolbutamide was devoid of action on the basal release of prostaglandin E2 from uterine strips and on the positive inotropic dose-response curve for added PGE2 or PGF2 alpha, constructed in presence of indomethacin (5 X 10(-6) M). The present findings do not permit a simple explanation regarding possible factors underlying the negative uterine inotropic influence of tolbutamide in the rat uterus. However, it appears that alterations in the integrity of tissue excitability and contractile apparatus, adrenergic implications, changes in uterine cAMP levels, inhibition of cyclo-oxygenase or low PEG2 synthesis and release, are not plausible mechanisms to explain the negative inotropism of tolbutamide. Therefore, it is suggested that the contractile depression evoked by tolbutamide and its action on the contractile effect of oxytocin might be linked to the impaired synthesis of other prostanoids, namely PGF2 alpha, PGI2 or PGD2, although the participation of not yet determined factor(s), namely changes in Ca2+ ion movements, cannot be discarded.
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PMID:Tolbutamide in vitro diminishes spontaneous and oxytocin-induced contractions of uterine smooth muscle from diestrous rats. 348 42

Endothelial cells of the arterial wall can generate vasodilator and vasoconstrictor substances. The prototype of a vasodilator substance formed primarily in the endothelium is prostacyclin, although its main target under physiological conditions are the platelets. In addition, the endothelial cells respond to a variety of neurohumoral mediators by the liberation of an unidentified substance(s) (endothelium-derived relaxing factor) with a potent inhibitory effect on vascular smooth muscle, presumably because it accelerates the production of cyclic GMP in the latter. Endothelium-derived relaxing factor is very unstable, and has an extremely short half-life. It is inactivated by plasma proteins and thus does not fulfill a hormonal role. A metabolite of arachidonic acid may be involved in the production of endothelium-derived relaxing factor. Among the neurohumoral mediators which release it are: acetylcholine (through activation of muscarinic receptors), adenosine di- and triphosphate (P2-purinergic receptors), bradykinin, histamine (H1- or H2-histaminergic receptors, depending on the species), serotonin (S1-serotonergic receptors), substance P, oxytocin, thrombin and vasopressin (V1-vasopressinergic receptors). The release of the factor can also be triggered by aggregating platelets (because they release adenine nucleotides and serotonin) and by increases in shear stress. It is likely that endothelium-dependent dilatation helps to prevent intraluminal coagulation in arteries with a normal intima. Absence, or dysfunction of the endothelium may favor the occurrence of vasospasm. Endothelium-dependent relaxations are reduced in atherosclerotic blood vessels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The endothelium and arterial reactivity]. 349 May 30

Current and emerging concepts on regulation of bovine corpus luteum function by various metabolites of arachidonic acid are reviewed. A series of experiments are presented which support the concept that prostacyclin (PGI2), a metabolite of arachidonic acid via the cyclooxygenase pathway, plays a luteotropic role, and that products of the lipoxygenase pathway of arachidonic acid metabolism, particularly 5-hydroxyeicosatetraenoic acid (5-HETE), play a luteolytic role in the function of the bovine corpus luteum (CL). These ideas are supported by the following findings: injection of PGI2 directly into CL at mid-cycle produced a prolonged increase in peripheral plasma concentrations of progesterone; PGI2 stimulated synthesis of progesterone by dispersed luteal cells; synthesis of PGI2 by luteal cells was greatest during the period of early CL development (d 5 and 10), and diminished as the CL aged unless pregnancy ensued, causing a maintenance of the CL and synthesis of PGI2; administration of indomethacin, a blocker of synthesis of prostaglandin by the cyclooxygenase pathway, twice daily on d 4 to 6 of the estrous cycle inhibited CL development and caused a reduction in cycle length, suggesting the presence of a luteotropic prostaglandin; oxytocin administration twice daily on d 4 through 6 inhibited CL development and was accompanied by a 50% reduction in luteal synthesis of PGI2 by CL collected on d 7; large quantities of 5-HETE were found in luteal tissue; the addition of 5-HETE to dispersed luteal cells inhibited synthesis of progesterone and PGI2, while production of PGF2 alpha was unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of luteal prostaglandins in the control of bovine corpus luteum functions. 353 77

The effects of prostacyclin (PGI2) on the uterine muscle of pregnant rats were studied in terms of uterine contraction and the variation in cyclic nucleotides. The following results were obtained: The administration of PGI2 stimulated the pregnant uterine muscle (in vitro). The oxytocic potency of PGE1-analog (ONO-802) was greatest, followed in order by that of PGF2 alpha and PGI2. The effect of 5-lypoxygenase inhibitor (AA-861) on uterine contraction was greatest under the administration of LTC4, followed in order by PGI2, oxytocin, PGF2 alpha, LTD4 and ONO-802. The effect of AA-861 was greater under the simultaneous administration of LTD4/LTC4 and ONO-802 than under the simultaneous administration of oxytocin and ONO-802. Terbutaline exerted the inhibitory effect on each of the oxytocies within two minutes in all cases. Its inhibitory effect on the oxytocics was slight in the cases to which oxytocin or ONO-802 was administered. Changes in cyclic nucleotides in the bath medium were determined before and after the administration of each drug. When PGI2 was administered, both c-AMP and c-GMP increased and showed a pattern which was different from that for other oxytocics. This tendency was also observed when PGI2 and other drugs (terbutaline, ONO-802 and AA-861) were administered together.
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PMID:[A basic study of the oxytocic effect of prostacyclin on the uterine muscle in pregnant rats]. 353 66


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