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)

Estradiol-17beta administration to young (10- to 12-week-old) rabbits to produce the "estrogen-dominated" uterus increased the uterine contractile response to both oxytocin and methacholine in vitro. In "progesterone-dominated" uteri, obtained from rabbits that received progesterone for 4 days after estrogen pretreatment, the contractile response to oxytocin in vitro was selectively abolished; the response to methacholine was unaffected. Parallel changes were observed in the concentration (but not affinity) of specific sites in uterine microsomal membranes that bind [(3)H]oxytocin with selectivity features expected for oxytocin receptors. Thus, estrogen-dominated uteri have an increased number of specific [(3)H]oxytocin binding sites per mg of membrane protein relative to untreated controls, whereas specific oxytocin binding sites are reduced to barely detectable levels in the progesterone-dominated uterus. Similar results are obtained when binding sites are measured in membranes from the myometrium of estrogen- or progesterone-dominated uteri. Short-term (24-hr) progesterone administration to estrogen-pretreated rabbits decreased, but did not abolish, specific [(3)H]oxytocin binding; the concentration of specific [(3)H]oxytocin binding sites was reduced without influence on the affinity of these sites. A sublethal dose of actinomycin D, administered over a 24-hr period to rabbits pretreated with estradiol for 4 days, likewise reduced specific oxytocin binding; additive effects were not observed when progesterone and actinomycin D were administered together. These results suggest that the regulatory effects of estrogens and progesterone upon the rabbit uterine contractile response to oxytocin are achieved, at least in part, by the opposing actions of these steroids in regulating the number of oxytocin receptors in smooth muscle cells. Estradiol increased the concentration of uterine oxytocin receptors; the maintenance of high receptor levels appears to depend upon the continuous de novo synthesis of oxytocin receptors. In contrast, progesterone, like actinomycin D, appears to act at the nuclear locus to repress synthesis of oxytocin receptors.
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PMID:Opposing effects of estradiol and progesterone on oxytocin receptors in rabbit uterus. 20 80

Rat and bovine adrenal cortical microsomal fractions isolated at 27,000 x g and 105,000 x g accumulated Ca2+ by a nonmitochondrial, ATP-dependent uptake system that was stimulated by ammonium oxalate. ACTH (2 mU/ml) significantly increased Ca2+ uptake in bovine adrenal cortical microsomes and in adrenal microsomes from acutely hypophysectomized rats, but only when the hormone was preincubated with intact tissue and not when it was added after homogenization. ACTH did not stimulate C2+ uptake in adrenal microsomes isolated from nonhypophysectomized, ether-stressed rats, in which basal Ca2+ uptake was higher than that observed in microsomes from hypophysectomized animals. The peptides oxytocin, insulin, and TSH did not stimulate Ca2+ uptake by adrenal cortical microsomes. ACTH preincubated with intact tissue had no effect on Ca2+ uptake in microsomes from liver, kidney, esophagus, or aorta. cAMP, 5'-AMP, and several other nucleotides, nucleosides, and related compounds stimulated adrenal cortical microsomal Ca2+ uptake by as much as 540% of control. The stimulatory effects of nucleotides, unlike those of ACTH, were apparent even when the agents were added after homogenization. However, like ACTH, the nucleotides were unable to stimulate Ca2+ uptake when they were added to isolated membrane vesicles during Ca2+ uptake measurements. It is suggested that the microsomal Ca2+ uptake system may respond to physiological stimulants and regulate Ca2+ availability in the intact cell.
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PMID:The effect of adrenocorticotropin and nucleotides on Ca2+ uptake in adrenal cortical microsomal vesicles. 21 5

A microsomal fraction resembling striated muscle sarcoplasmic reticulum was isolated from uterine smooth muscle. ATP induces calcium accumulation in this fraction. Increased temperature enhances calcium accumulation and calcium-activated ATPase. In the absence of ATP, approximately 35% of the intrinsic calcium exchanges with the 45Ca in the incubation medium. In the presence of ATP, exchange of intrinsic calcium with 45Ca increases by an amount which equals the ATP-dependent calcium binding. In preparations partially preloaded with calcium, a steady state of bound calcium is reached when the ATP is exhausted. Calcium is released under these conditions by prostaglandins E2 and F2alpha, but not by PGF1beta. The antibiotic ionophores X537A and A23187, as well as oxytocin, also release calcium previously accumulated under ATP stimulation. None of these agents, with the exception of oxytocin, release intrinsic calcium. Thus, the effect of prostaglandins resembles that of the ionophores, suggesting an ionophoretic action of these prostaglandins. The release of calcium conforms with the in vivo smooth muscle contracting action of these agents.
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PMID:Effects of prostaglandins and oxytocin on calcium release from a uterine microsomal fraction. 32 Feb 10

A microsomal fraction was prepared from human pregnant uteri at term and at 6 to 19 weeks' gestation, and from nonpregnant uteri by differential centrifugation and purified on a discontinuous sucrose density gradient. This fraction bound calcium in the presence of adenosine triphosphate (ATP). ATP-dependent calcium binding in microsomal preparations was found to increase with advancing pregnancy. Addition of progesterone increased the ATP-dependent calcium binding, while addition of oxytocin decreased the ATP-dependent calcium binding. In combination, oxytocin and progesterone counteracted each other. The progesterone effect was specific for progesterone; three biologically inactive analogues had no effects on calcium binding. The actions of progesterone and of oxytocin on ATP-dependent calcium binding were found to be consistent with their respective in vivo uterine relaxing and contracting actions.
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PMID:Calcium accumulation by human uterine microsomal preparations: Effects of progesterone and oxytocin. 42 14

The enzymic inactivation of oxytocin by liver, kidney, uterus and pancreas homogenate subcellular fractions of hens was studied. Oxytocin was most rapidly degraded by the soluble fraction of tissues examined. All the subcellular fractions of liver and kidney inactivated oxytocin, but only the microsomal and soluble fractions of uterus and pancreas showed the oxytocin-inactivating activity. The location of enzymes inactivating oxytocin in subcellular fractions of hen tissues was investigated with the aid of synthetic analogues of oxytocin (deamino-oxytocin and deamino-carba1-oxytocin). The carboxamidopeptidase activity, hydrolyzing the amide bonds in the linear portion of oxytocin was located in the soluble fraction of hen liver, kidney and uterus. No carboxamidopeptidase activity in the pancreatic soluble fraction was found. These results showed that aminopeptidase activity is bound to heavy subcellular particles in the hen tissue. An action of unknown endopeptidases was observed in the microsomal fraction of uterus and pancreas.
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PMID:Inactivation of Oxytocin and its analogues by subcellular fractions of hen tissues. 108 26

Rat neural lobes have been separated into subcellular fractions by differential centrifugation at various times after an intracisternal injection of [35S]cysteine or [3H]choline. Both isotopes led to a rise and fall in the radioactivity of neurosecretory granules (NSG) which paralleled that found previously for the neurohypophysial hormones and the neurophysins. While the radioactivity of the NSGs resulting from [35S]cysteine injection was predominantly associated with granular contents, [3H]choline injections led to a preferential labelling of the granular membrane. There was no indication of a sequential movement of radioactivity from the NSG-membrane fraction into the microsomal fraction (containing the so-called small vesicles) which might be expected if granular membrane were recaptured as small vesicles after release of secretory product by exocytosis. When release was stimulated in injected animals by giving them 2% NaCl solution to drink, 35S diappeared from the gland as expected, but 3H was retained and, moreover, appeared in the NSG-membrane fraction; results compatible with membrane conservation occurring by recapture of large vesicles. There was an indication that some of the neurophysin in the NSG was membrane-bound and that this too was retained after release of the granular contents.
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PMID:Incorporation of radioactive precursors into the membrane and contents of the neurosecretory granules of the rat neurohypophysis as a method of studying their fate. 125 66

The hydrolysis of oxytocin by human placental subcellular fractions was studied in the presence of selective inhibitors by measuring liberated amino acids by high performance liquid chromatography (HPLC). Oxytocin degradation by microsomal and lysosomal fractions was inhibited by bestatin, amastatin and puromycin. The IC50 values of these inhibitors on oxytocin degradation by both fractions were similar to those of these inhibitors on the human placental aminopeptidase M measured by L-Leu-p-nitroanilide as a substrate (LAP activity), which we reported previously. However, purified aminopeptidase M from human placental microsomal fractions could not liberate any amino acid from oxytocin. Since phosphoramidon (1 mumol/l), a putative metalloendopeptidase inhibitor, and N-benzylcarbonyl-valyl-prolinal (Z-Val-prolinal) (14 mumol/l), a selective inhibitor of post-proline endopeptidase, could not significantly influence the degradation of oxytocin by either subcellular fractions, neither enzyme seems to be actively involved in oxytocin degradation. These results strongly suggested the existence of oxytocinase(s) other than the above three enzymes in microsomal and/or lysosomal fractions of human placenta.
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PMID:Degradation of oxytocin by the human placenta: effect of selective inhibitors. 135 23

The effects of N-acetylimidazole on specific binding of oxytocin to microsomal fractions of bovine mammary gland were studied. N-acetylimidazole suppressed oxytocin binding, with time and concentration dependence. Decreased oxytocin binding activity appeared to be due to decreased affinity of the hormone for its receptor. Acetylation of oxytocin, rather than of oxytocin receptors, seemed to be responsible for the decreased binding.
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PMID:Effects of N-acetylimidazole on oxytocin binding in bovine mammary tissue. 196 76

The maturity of the hypothalamic-neurohypophyseal system in the first 10 days of the postnatal life of rats was analysed through the potential inhibitory effect of ethanol on oxytocin and vasopressin secretion. Experimental animals were intraperitoneally injected with ethanol, and the control ones with the corresponding amount of physiological solution. Hypophyses were extracted 30 min later to be histologically analysed. Although the morphological features of neurohypophysis with functionally active pituicytes and dense vascular net were present even from the first natal day, neurosecretory grains were noticed not before the 8 th day. But the inhibitory effect of ethanol on neurosecretion did not manifest itself until the 10 th day, so it can be concluded that in this period the hypothalamic-neurohypophyseal system had not yet reached its level of complete maturity. Fatty acids in pituicytes being elements of neurohypophyseal neuroglia are pronunced even in animals younger than 10 days, which indicates that their origin could not be necessarily linked to the process of neurosecretion. In acutely alcoholized offsprings the amount of fatty acids in the neurohypophysis was reduced. This is substantiated by the engagement of the alcohol dehydrogenase (ADH) and the microsomal ethanol-oxidizing system (MEOS) in alcohol metabolism with which follows retarded oxidation process of fatty acids.
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PMID:[Reactive characteristics of the neurohypophysis in the early postnatal period]. 228 3

Luteinizing hormone is the major regulator of Leydig cell differentiation and steroidogenic function. A number of hormones produced by the Leydig cell (e.g. estrogen, angiotensin, CRF, vasopressin) and the tubular compartment (inhibin, TGF beta), can influence both acute and long-term actions of LH. Conversely, hormones produced in the Leydig cells modulate tubular function (e.g. androgen, beta-endorphin, oxytocin). The LH stimulatory event can be negatively influenced by the action of angiotensin II through the guanyl nucleotide inhibitory unit of adenylate cyclase. We have recently discovered an action of corticotrophin releasing hormone through specific high-affinity low-capacity receptors in the Leydig cells which involves a pertussis toxin insensitive guanyl nucleotide regulatory unit with interaction between signalling pathways and resulting inhibition of LH induced cAMP generation and consequently of steroidogenesis. In contrast to other tissues the CRF receptor in the Leydig cells did not couple to Gs. CRF action is exerted through direct or indirect action of protein kinase C, at the level of the catalytic subunit of adenylate cyclase. Physiological increases in endogenous LH cause positive regulation of membrane receptors and steroidogenesis, while major elevations in circulating gonadotropin can induce down-regulation of LH receptors and desensitization of steroid responses in the adult cell. Gonadotropin-induced desensitization in adult rat tests include an estrogen mediated steroidogenic lesion of the microsomal enzymes 17 alpha-hydroxylase/17,20-desmolase. For further understanding of the regulation of this key enzyme of the androgen pathway the rat P450(17) alpha cDNA was cloned and sequenced. This cDNA expressed in COS-1 cells 17 alpha-hydroxylase/17,20-desmolase activities. From the deduced amino acid sequence, two transmembrane regions were identified, a signal peptide for insertion in the ER, and a 2nd transmembrane region separated from the first by 122 amino acids. The carboxy terminal non-transmembrane region possesses 4 hydrophobic clefts, of which cleft II would contain the putative steroid binding site for both hydroxylase and lyase activities. The rat cDNA was employed to evaluate the hormonal regulation of mRNA levels in adult and fetal Leydig cells. Low dose hCG treatment caused an early increase in mRNA levels followed by a return to control values at later times, while with higher desensitizing doses the initial increase in mRNA was followed by a marked reduction in mRNA at 24 h and a small recovery at 48 h. Fetal rat Leydig cells treated with E2 showed a 70% decrease in P450 mRNA levels, and testosterone production closely followed the changes in mRNA.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:LH action in the Leydig cell: modulation by angiotensin II and corticotropin releasing hormone, and regulation of P450(17) alpha mRNA. 269 45


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