Disorders of antidiuretic hormone secretion.
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Blood Volume↗
Biomedical subjects
A G Robinson
Publications and source records attributed to A G Robinson.
A novel oxytocin-like and vasotocin-like peptide in human plasma after administration of estrogen.
Using three antisera to oxytocin (OT Pitt Ab-1, OT Pitt Ab-2, and TOR OT Ab), we found comparable levels of OT in response to infant suckling and during infusion of synthetic OT, and identical standard curves with biological and synthetic standards of OT. Pitt Ab-1, but not Pitt Ab-2 or TOR OT Ab, measured increased OT in response to estrogen. Using an arginine vasotocin RIA (TOR AVT Ab), we found an increase in AVT immunoreactivity after estrogen treatment. Mean basal OT levels measured with OT Pitt Ab-2 in plasma of men [0.75 +/- 0.06 (+/- SEM) microU/ml] and women (0.8 +/- 0.09 microU/ml) were lower than OT measured with Pitt Ab-1 (1.7 +/- 0.09 microU/ml in men and 1.7 +/- 0.07 microU/al in women; P less than 0.001). Mean OT measured with Pitt Ab-2 in the plasma of women given estrogen chronically (0.8 +/- 0.04 microU/ml) and acutely (0.6 +/- 0.15 microU/ml) were not significantly different from basal levels. OT levels measured with Pitt Ab-1 in the same samples were 4.6 +/- 0.5 and 4.3 +/- 0.5 microU/ml, respectively, both significantly increased from basal levels (P less than 0.001) and significantly higher than OT measured with Pitt Ab-2 (P less than 0.001). Mean OT measured with Pitt Ab-1 in the plasma of pregnant women was 8.6 +/- 1.02 microU/ml, significantly higher than OT measured with Pitt Ab-2 (1.0 +/- 0.3 microU/ml; P less than 0.001). Men given 25 mg diethylstilbestrol had significant increases in OT measured with Pitt Ab-1 and in AVT measured with TOR AVT (P less than 0.01), but not in OT measured with Pitt Ab-2. Plasma from a man given diethylstilbestrol was prepared for high performance liquid chromatography and applied to a C18 muBondapak reverse phase column. The plasma contained two peaks of immunoreactivity detected as OT with Pitt Ab-1 and as AVT using TOR AVT Ab. The material was not detected by Pitt Ab-2 or TOR OT Ab and did not coelute with standards of OT, AVT, or AVP. Pregnancy plasma, thioglycolic acid, chymotrypsin, and trypsin reduced Pitt Ab-1, Pitt Ab-2, and TOR OT immunoreactivity of synthetic OT. The percent recovery of OT immunoreactivity was not significantly different with Pitt Ab-1 vs. Pitt Ab-2. A novel peptide, which is increased in response to administered estrogen, is present in human plasma and is detected by some antisera to OT and AVT. The observation explains the wide variability in OT levels in the estrogen-primed state and provides a new mechanism to study estrogen-related physiology and pathophysiology.
Adult↗
High pressure liquid chromatographic separation of an oxytocin/arginine vasotocin-like peptide from the plasma of patients with chronic renal failure.
Levels of a novel oxytocin (OT)- and arginine vasotocin (AVT)-like peptide detected by one antiserum to OT (Pitt Ab-1) and one antiserum to AVT (Tor AVT) were recently found to rise in human plasma in response to administration of estrogen. The novel peptide rose in parallel with the estrogen-stimulated neurophysin (ESN). The mean level (+/- SEM) of ESN in plasma of 11 individuals with altered renal function (nondialyzed) was significantly higher than the level in individuals with normal renal function (4.2 +/- 0.9 vs. 1.1 +/- 0.04 ng/ml; P less than 0.01). In patients treated with hemo- or peritoneal dialysis, mean (+/- SEM) levels of ESN were 18.1 +/- 3.2 and 16.8 +/- 3.7 ng/ml, respectively. Levels of estradiol and estrone were not elevated and did not correlate with high levels of ESN. Levels of OT Pitt Ab-1, AVT, and ESN immunoreactivity were measured in plasma form nine patients undergoing hemodialysis and eight patients undergoing peritoneal dialysis. Mean (+/- SEM) levels of all three peptides were elevated (12.9 +/- 1.5 microU/ml, 32.1 +/- 6.7 pg/ml, and 13.5 +/- 4.0 ng/ml, respectively). ESN was significantly correlated with OT Pitt Ab-1 and AVT (R2 = 0.80; P less than 0.001). Plasma samples from the same patients were pooled, treated, and separated by reverse phase HPLC. The plasma contained a peak of immunoreactivity detected by Pitt Ab-1 and Tor AVT Ab. The position of the material was distinct from that of synthetic OT, AVT, or AVP and corresponded to the position of the novel OT-like peptide found in plasma of individuals given estrogen. The findings support parallel secretion of the OT-like peptide with ESN and represent the first disease state characterized by high levels of this OT- and AVT-like peptide.
Adult↗
Neurohypophysial hormones in cerebrospinal fluid of adults: absence of arginine vasotocin and of a diurnal rhythm of arginine vasopressin.
We previously reported a prominent diurnal rhythm of oxytocin (OT) in human cerebrospinal fluid (CSF) similar to the brisk CSF OT rhythm in monkeys. An OT CSF rhythm has not been found in lower species. In contrast, a pronounced arginine vasopressin (AVP) rhythm has been found in lower species, but the AVP CSF rhythm is less marked in subhuman primates. In patients (n = 7) in whom lumbar drains had been temporarily placed for treatment of CSF rhinorrhea, we obtained CSF samples every 6 h. In 6 of these 7 patients, we previously reported (1) finding a prominent CSF OT rhythm, with a peak at 1200 h, by analysis of variance of repeated measures. When the samples of CSF of these same 6 patients (plus 1 additional patient) were assayed for AVP, no AVP rhythm was found. We also measured AVP, OT, and arginine vasotocin (AVT) by RIA in single samples of CSF obtained from 23 other patients. In these single samples of CSF, mean AVP was 0.9 +/- 0.11 (+/- SEM) pg/ml, and OT was 3.7 +/- 0.5 microU/ml. CSF AVT immunoreactivity was 0.6 pg/ml or less in the 23 patients. Two pools of CSF were separated by reverse phase high pressure liquid chromatography. The peak OT and AVP, as determined by RIA, coeluted exactly with synthetic and human posterior pituitary OT and AVP, respectively. No immunoreactive AVT was found in the position of synthetic AVT in the eluates. Thus, OT and AVP are present in human adult CSF, but AVT is not. The lack of a prominent rhythm of AVP in human CSF is in marked contrast to the brisk OT rhythm. The rhythm of neurohypophysial peptides in human and subhuman primates is different from the rhythm in lower species, suggesting different functions for OT and AVP in the central nervous system of various species.
Adult↗
Desmopressin.
Desmopressin (dDAVP), a synthetic analog of the neurohypophyseal nonapeptide arginine vasopressin, has enhanced antidiuretic potency, markedly diminished pressor activity, and a prolonged half-life and duration of action compared to the natural hormone. Desmopressin is the treatment of choice for central diabetes insipidus and can be administered either intranasally or parenterally. A newly approved indication is treatment of mild classical hemophilia and von Willebrand's disease, in which deficient concentrations of factor VIII and von Willebrand's factor are transiently increased to levels that allow minor surgery.
Anemia, Sickle Cell↗
Oxytocin augmentation of dysfunctional labor. IV. Oxytocin pharmacokinetics.
Plasma oxytocin levels ([OT[p) were measured every 20 minutes during infusions of oxytocin. The initial dose of 1 mU/min was incremented, if necessary, by 1 mU/min at 40-minute intervals until sufficient contractility was obtained to effect cervical dilatation. The results demonstrated: the [OT]p rises linearly with each dose for the first 40 minutes of the infusion; there is no difference between the 40- and 60-minute sample values, suggesting that the peak [OT]p of each dose is achieved in 40 minutes; the increment in [OT]p required to produce effective contractility varies widely from 0.58 to 5.09 microU/ml; the plasma clearance rate varied from 11.2 to 32.5 ml/kg/min. Approximately 40 minutes is required for any particular dose of oxytocin to reach a "steady-state" [OT]p and the maximal uterine contractile response. The design of regimens for the augmentation or induction of labor should be based on this knowledge.
Cervix Uteri↗
Intracranial and systemic effects of hetastarch in experimental cerebral edema.
These experiments were done to determine the effectiveness of oncotic and oncotic/diuretic ( oncodiuretic ) therapy in dogs with experimental cerebral edema induced by a cold lesion. Dogs were divided into 3 groups and were treated for 6 h with either crystalloid (control group), a 12% hetastarch solution, or a 24% hetastarch solution plus furosemide. The cerebral effects of treatment were evaluated by intracranial pressure (ICP) measurements and by autopsy measurements of brain density and brain water content. The systemic effects were evaluated by measuring fluid balance, wedge pressure, hematocrit, free-water clearance, and serum vasopressin level. Hetastarch and hetastarch /furosemide significantly reduced ICP, increased brain density, and decreased water content of the edematous brain. Hetastarch alone caused a positive fluid balance and marked hemodilution but did not normalize vasopressin levels, whereas hetastarch /furosemide caused a marked diuresis without changing the hematocrits, and normalized vasopressin levels. Oncodiuretic therapy, in contrast to traditional fluid restriction, seems to decrease ICP effectively by causing normovolemic dehydration.
Animals↗
Levels of the oxytocin-associated and vasopressin-associated neurophysins in plasma and their responses in essential hypertension.
A group of 89 individuals with essential hypertension was evaluated with several measurements including the neurophysin believed to be the human oxytocin neurophysin (OT-Np), and the human vasopressin neurophysin (VP-Np). The neurophysins are proteins synthesized within cells of the supraoptic and paraventricular nuclei in conjunction with their respective hormones oxytocin and vasopressin as part of a common precursor molecule and so may reflect the simultaneous presence in plasma of their associated hormones. A poor but statistically significant correlation was noted between levels of OT-Np and renin activity in plasma (PRA) either supine (r = 0.248) or erect (r = 0.255). Levels of OT-Np averaged 1.75 ng/ml and were inversely correlated with creatinine (r = -0.252), supine blood pressure (r = -0.450), plasma volume (r = -0.327), and 24-hour urine sodium (r = -0.313). Levels of Ot-Np could be suppressed by infusion of physiologic saline. Levels of OT-Np were lower in the volume expanded state and were positively correlated with the quantity of sodium excreted into a 24-hour urine collected after the infusion (r = 0.426) and inversely correlated with the supine systolic (r = -0.379) and supine diastolic (r = -0.455) blood pressures recorded after the infusion of saline. Oestrogen, a stimulus to the secretion of OT-Np, did not account for the elevation of OT-Np observed in the study, since mean levels of oestradiol (E2) in a subset of the patients with elevated OT-Np (E2 = 36 pg/ml) were not different from levels in subjects with lower values of OT-Np (E2 = 45 pg/ml).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Studies of oxytocin in plasma of women during hypocontractile labor.
Oxytocin (OT) was measured by RIA in plasma of women during hypocontractile labor before and during graded doses of iv infused synthetic OT. Based upon in vitro studies of recovery of OT from pregnancy plasma, blood was collected into heparinized tubes which were kept at 4 C. The addition of EDTA and phenanthrolene to an aliquot of each sample resulted in measured levels of OT in plasma that correlated closely with levels measured in the absence of these reagents (r2 = 0.86). Comparison of OT levels in plasma of normal individuals determined in the presence and absence of these reagents also yielded a high degree of linear correlation (r2 = 0.97). The mean level of OT in 11 women during hypocontractile labor before the infusion of OT was 1.01 +/- 0.31 (+/- SEM) microU/ml. There was a linear correlation between the dose of OT infused and the level of OT in plasma with infused doses of OT between 1 and 4 mU/min (r2 = 0.99). The time of onset of adequate uterine contractility was recorded by on-line computer analysis, and the level of OT in plasma obtained simultaneously was variable among the women. The mean OT MCR in these women was 17.4 +/- 9.2 (+/- SEM) ml/kg X min, similar to the MCR in normal men (17.6 +/- 2.1 ml/kg X min). Levels and pharmacokinetics of OT during hypocontractile labor were similar to those in nonpregnant individuals and women in late pregnancy. The variability in OT concentrations at the time of adequate uterine contractility suggests that individual myometrial sensitivity is an important determinant of the response to administered OT in humans.
Adult↗
Hyponatremia and natriuresis following subarachnoid hemorrhage in a monkey model.
A monkey model of subarachnoid hemorrhage (SAH) was used to study both the incidence of hyponatremia and natriuresis and the associated changes in antidiuretic hormone (ADH) secretion and salt and water balance. Following SAH, seven of nine monkeys became natriuretic and hyponatremic. The natriuretic period lasted an average of 4.4 +/- 0.4 days. The mean nadir of serum sodium content was 125.7 +/- 1.6 mEq/liter, and occurred on the average on the 5th day following SAH. The sodium balance after SAH was negative as compared to the preoperative positive sodium balance (p less than 0.001). The plasma vasopressin level was usually elevated for a day following surgery, but there was no significant difference in the levels during the preoperative period and during the period of natriuresis following SAH. The daily urine output and aldosterone levels were not significantly different, and the plasma volume was slightly, but not significantly, decreased after SAH. Four of the animals that had a hyponatremic and natriuretic response following SAH showed a normal regulation of vasopressin in response to both a water challenge and hypertonic saline challenge. The three monkeys that underwent sham procedures did not become hyponatremic and natriuretic postoperatively. The sham-operated monkeys did not show significant differences in their plasma vasopressin levels, urine volume, plasma volume, and aldosterone levels following surgery. These observations are more consistent with primary natriuresis as the cause of hyponatremia rather than the syndrome of inappropriate secretion of ADH. The cause of the renal loss of sodium is not known, but the possibility of a brain natriuretic factor or an alteration in the neural control of the kidney should be considered.
Animals↗
Intracranial and systemic effects of osmotic and oncotic therapy in experimental cerebral edema.
Experiments were carried out to compare the effectiveness of oncotic and osmotic therapy in dogs with experimental cerebral edema caused by a left parietal cold lesion. Animals were divided into five groups and treated for 6 hours with either crystalloid (control group), or mannitol, albumin, furosemide, or albumin/furosemide (treatment groups). The cerebral effects of therapy were evaluated by intracranial pressure (ICP) measurements and by postmortem evaluations of water content, using computerized tomography (CT) density measurements and wet-dry weight measurements. The ICP was significantly reduced by all treatments except albumin alone, and was reduced equally by mannitol, furosemide, and albumin/furosemide. The CT density of the lesion area was significantly increased by all treatments. The density of the contralateral nonlesioned hemisphere was significantly increased by all treatments except albumin. The water content of the lesion area was significantly decreased by all treatments; water content of the opposite hemisphere was not significantly reduced. The systemic effects of therapy were evaluated by measuring net fluid balance, wedge pressures, hematocrits, free water clearance, and vasopressin. Negative fluid balance without an increase in hematocrit or in vasopressin secretion occurred only in dogs treated with albumin/furosemide. Such oncodiuretic therapy seems to cause normovolemic dehydration and to have cerebral effects similar to mannitol and furosemide, without their undesirable systemic effects.
Albumins↗
Human pituitary neurophysin precursors.
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Animals↗
Quantitation of changes in the content of neurohypophyseal peptides in hypothalamic nuclei after adrenalectomy.
In adrenal insufficiency there is an increase in the content of vasopressin in the external zone of the median eminence as determined by immunohistology. We studied rats after bilateral adrenalectomy and obtained punched samples of the supraoptic, the paraventricular, and the suprachiasmatic nuclei, and from the median eminence and the posterior pituitary. Vasopressin, neurophysin and oxytocin were all decreased in content in the posterior pituitary but in the suprachiasmatic nucleus and in the median eminence there was a significant increase in the content of vasopressin. The increased levels of vasopressin in the median eminence are interpreted as representative of the content in axons and demonstrate a large increase of transport of vasopressin. In the SON and PVN there was no increase in the content of vasopressin during this state of augmented synthesis and transport, indicating that vasopressin moves rapidly from the site of synthesis into the transport system. The increased content of vasopressin in the suprachiasmatic nucleus shows that vasopressin at this level also varies with changes in adrenal function. Levels of oxytocin throughout the neurohypophysis did not change in parallel with vasopressin demonstrating relatively selective responses of the neurohypophyseal hormones.
Adrenalectomy↗
Characterization of neurophysin-vasopressin prohormones in human posterior pituitary tissue.
To better characterize putative neurophysin-vasopressin prohormones in human posterior pituitary tissue, we extracted human posterior pituitary glands in 0.1 M HCl and isolated the higher molecular weight neurophysin-immunoreactive proteins. Sephadex G-75 gel filtration in 0.1 M formic acid with 6 M urea showed four distinct peaks of neurophysin immunoreactivity. Analysis of isolated lyophilized fractions of these peaks by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed neurophysin-immunoreactive proteins at molecular weights of 10,000 daltons (79-87% of the total neurophysins), 19,000-20,000 daltons (10-16%), 26,000-30,000 daltons (1-2%), and a broad range of 30,000- to 100,000-dalton immunoreactivity from the void volume (V0) peak (2-3%). The 19,000- to 20,000-dalton and 26,000- to 30,000-dalton proteins were stable after both heating and treatment with reducing agents, but could be converted by chymotrypsin proteolysis to 10,000-dalton neurophysins and 3,000- to 5,000-dalton AVP-immunoreactive proteins. In contrast, the neurophysin immunoreactivity in the V0 peak was broken down to lower molecular weight neurophysin- and AVP-immunoreactive proteins by heating alone. Extraction of human posterior pituitaries in the presence of either [125I]human AVP-neurophysin or [35S] cysteine-labeled monkey neurophysin showed that no labeled neurophysin eluted in the areas of the 19,000- to 20,000- or 26,000- to 30,000-dalton proteins, but a significant fraction of the [35S]monkey neurophysin eluted in the V0. These data suggest that the 19,000- to 20,000- and 26,000- to 30,000-dalton human neurophysins represent stable proteins which are probably common precursor molecules for neurophysin and AVP, but the greater than 30,000-dalton neurophysins found in the V0 appear to be aggregates of neurophysins, neurophysin precursors, AVP, oxytocin, and probably other proteins and lipids as well, rather than very high molecular weight precursor proteins.
Animals↗
A time-dependent peak of oxytocin exists in cerebrospinal fluid but not in plasma of humans.
Oxytocin (OT) and the oxytocin-neurophysin (OT-Np) were measured by RIA in samples of cerebrospinal fluid (CSF) obtained sequentially at 0600, 1200, 1800, and 2400 h from six patients in whom intrathecal catheters were temporarily placed for CSF rhinorrhea. The highest levels of OT in CSF were found at 1200 h. An analysis of variance of sequential measures of the concentration of OT in samples of CSF obtained every 6 h over a 30-h period showed the mean levels (+/- SEM) of OT at 1200 h, 6.41 +/- 1.13 microU/ml and 5.06 +/- 0.58 microU/ml, to be significantly higher (p less than 0.05) than mean levels of OT at 0600 h, 2.50 +/- 0.65 microU/ml; 1800 h, 2.63 +/- 0.61 microU/ml and 2.64 +/- 1.21 microU/ml; and 2400 h, 2.86 +/- 1.13 microU/ml. The levels of OT-Np in CSF did not show a similar peak. In three of the patients simultaneous samples of blood were obtained for measurement of the same peptides, but no corresponding peak of OT or its Np was found in plasma of these three patients. The level of OT in CSF at all times was also significantly higher (p less than 0.05) than the level of OT in plasma of these three patients. Levels of OT and OT-Np were measured by RIA of samples of plasma obtained hourly for a 24-h period from six healthy men and six healthy women. No diurnal variation of OT or its Np in the plasma of men or women was found. This pattern of OT in the CSF of humans is similar to the pattern of OT in the CSF of the Rhesus monkey, but in contrast to the lack of a clearly defined peak of OT in the CSF of the cat or the rat. These observations in humans reinforce the differences among species of the secretion of OT in the CSF.
Adult↗
Abscess formation within pituitary tumors.
Three consecutive cases where abscesses were found within pituitary tumors are presented. In all cases, the diagnosis was made preoperatively and the patients were begun on stress doses of hydrocortisone and antibiotics before surgical drainage of the abscess. All patients recovered with minimal neurological deficits. Review of the literature reveals that the diagnosis is seldom made preoperatively or before autopsy and is associated with high mortality and morbidity. Early suspicion of a pituitary abscess leading to early treatment with antibiotics and operative drainage seem to be important factors in decreasing this high mortality and morbidity.
Abscess↗
Factors in predicting outcome from operation in patients with prolactin-secreting pituitary adenomas.
Forty female patients with pituitary adenomas were studied retrospectively to determine whether factors could be identified that would help predict outcome from operation. Twenty-five patients had a normal prolactin level (less than or equal to 30 ng/ml) during the early postoperative period (less than or equal to 3 months) and 15 patients had persistent disease (prolactin greater than 30 ng/ml). Nine of the 25 patients who initially had normal prolactin levels during the early postoperative period were found to have elevated prolactin levels during the late postoperative period (greater than 3 months). As has been shown previously, tumor size and preoperative prolactin levels were important factors in predicting surgical outcome. Patients with smaller (Hardy Grades I and II) tumors had significantly better outcome than those with larger (Hardy Grades III and IV) tumors. Patients with successful surgical outcomes had significantly lower preoperative prolactin values (204 ng/ml) than those with operative failures (524 ng/ml). In addition to the known factors, the patient's age at the time of operation, the length of amenorrhea, and the patient's growth hormone response to insulin hypoglycemia were newly identified as factors that helped predict surgical outcome. Patients who were less than or equal to 26 years of age and who had had amenorrhea for less than or equal to 6 years at the time of operation had significantly better surgical outcomes. Patients with normal growth hormone responses to stimulation testing had significantly better surgical outcomes than those with a blunted preoperative growth hormone response. The data suggest that prolactin-secreting pituitary tumors may cause a progressive disorder for which operative cure may be obtained only early in the disease.
Adenoma↗
Prolactinomas in women: current therapies.
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Adenoma↗