Biological and immunological studies of lipid-containing neurophysin of rat and reaggregated lipid complex.
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Biomedical subjects
Publications and source records attributed to A G Robinson.
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Acromegaly is caused by hypersecretion of growth hormone by the pituitary. There is some debate as to whether the primary etiology of the disease is abnormal hypothalamic stimulation of the pituitary or a primary pituitary tumor. This paper presents a case of acromegaly in which growth hormone dynamics in response to stimulation and suppression tests were abnormal. After transsphenoidal adenomectomy of a small tumor, growth hormone levels returned to normal and suppression and stimulation test results reverted to normal within 1 wk postoperatively and remained normal for 2 yr. The findings suggest that the acromegaly in this case was due to a primary pituitary dysfunction. Microsurgical removal of growth-hormone-secreting tumors provides a unique opportunity to study the etiology of acromegaly.
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Renal cAMP concentration and renal prostaglandin (PG) E2 and PGF2alpha production were determined in control rats and rats with surgically induced myxedema. Slices from the kidneys of each group were incubated in vitro. cAMP concentration of inner medullary slices from the kidneys of myxedematous rats was decreased in comparison to slices from control rats. There was no difference between the two groups when slices from outer medulla and cortex were compared for cAMP level. In myxedema, there was decreased inner medullary production of PGE2, but not PGF2alpha. The difference in PGE2 production between myxedema and control rat kidneys was not corrected by addition of either arachidonic acid (170 micronM) or phospholipase A2 (5 microgram/ml). Arachidonic acid, however, increased inner medullary cAMP concentration in myxedema kidneys to a value not measurably different from control. Thus, there appears to be a decreased PGE2 production in the renal inner medulla of rats with myxedema. In view of the fact that PGE2 has previously been shown to increase inner medullary cAMP content, the reduced inner medullary content of cAMP would appear to be attributable to reduced PGE2 production.
Impaired excretion of a water load is known to occur in adrenal insufficiency and to be corrected by administration of glucocorticoid. Such impairment has been related to either a loss of a permissive effect of glucocorticoids on the diluting segments of the nephron or to an alteration of release, turnover, or action of antidiuretic hormone. Specific and sensitive RIAs for arginine vasopressin and neurophysin were utilized to measure plasma and pituitary levels of neurohypophyseal peptides at baseline and after an intragastrically administered water load. Conscious, unanesthetized, and nonstressed sham-operated, adrenalectomized, and adrenalectomized prednisone-treated rats were studied. The results demonstrate a significant elevation in vasopressin and neurophysin in plasma in adrenalectomized rats maintained in a normal state of hydration. After water loading, the adrenalectomized rats diluted their plasma osmolality but had a decreased urinary volume, increased urinary osmolality, and elevated vasopressin and neurophysin in their plasma. In the pituitary, vasopressin and neurophysin were depleted in adrenalectomized rats, indicating increased secretion of these peptides. It is concluded that elevated vasopressin in plasma may be an important factor in the incomplete water diuresis in adrenal insufficiency.
DDAVP, 1-desamino-8-D-arginine-vasopressin, is a synthetic analog of arginine vasopressin which produces prolonged antidiuresis after intranasal administration to patients with complete central diabetes insipidus. We have studied the mechanism of the prolonged antidiuretic effect by specific radioimmunossay of DDAVP in plasma of patients and by in vitro studies on the adenylate cyclase-cylic AMP system of the rat outer renal medulla. When DDAVP was administredd to patients, all responded, but the duration of response among patients varied from 5-21 h. The peak level of DDAVP in plasma was achieved up to 4 h after administration indicating a slow absorption from the nasal mucosa. The disappearance time of DDAVP from plasma correlated significantly with the duration of antidiuresis, P less than 0.001. On a molar basis DDAVP was 3-fold greater than AVP in its stimulation of outer medullary adenylate cyclase activity and 10-fold greater than AVP in its stimulation of cyclic AMP content. The prolonged antidiuresis of intranasally administered DDAVP is due to slow absorption, presistence in plasma, and enchanced effect on the kidney.
A case is presented and 11 others are reviewed in which symptomatic pituitary tumor enlargement occurred during pregnancies that resulted from induced ovulation. The syndrome is usually characterized by headache and visual disturbances with bitemporal visual field abnormalities, but may present with ocular muscle palsies. The cases are divided into two groups. The patients in one group had a shorter duration of amenorrhea (3.8 years), developed symptoms before the 14th week of pregnancy, and were usually treated by tumor removal. Patients in the second group had a longer period of amenorrhea (10.2 years), developed symptoms after the 24th week of pregnancy, and their symptoms regressed with delivery of the infant. Tumor removal or termination of the pregnancy both resulted in resolution of symptoms. All pregnancies resulted in normal infants. This series provides guidelines for management of future cases.
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A continuous cell culture line was established from a bone marrow metastasis of small cell anaplastic carcinoma of the lung. The cultures were characterized by light and electron microscopy, and an unusual concentric arrangement of cells was observed, both in sectioned material from the patient's tumor and from the cell cultures. The cells had two types of specialized cell junctions and contained secretory-like granules of the type described in neuroendocrine cells. Lactic dehydrogenase isozyme patterns were the same as those observed in normal human serum, and the karyotype revealed the presence of several marker chromosomes. Vasopressin was present in the cells and secreted into the culture medium in the absence of neurophysin, as shown by the immunoperoxidase technique and radioimmunoassay. Oxytocin was also absent from cells.
Ten suspected suprasellar mass lesions were evaluated by CT cisternography (CTC). In each case the cisterns could be defined. Suprasellar mass lesions were found in six. Precise assessment of the anterior, lateral, posterior, and superior extent, made by metrizamide CTC, was verified at surgery. In two masses the intravenously enhanced scan was not diagnostic, while a lesion was visualized by intrathecal (metrizamide) CT. The major diagnostic entity was an enlarged third ventricle. When a chiasmic lesion is suspected and the conventional scan is negative, metrizamide CTC is the examination of choice.
Rat posterior pituitaries were extracted in acid and total rat neurophysins were isolated. Preparative disc gel electrophoresis separated the total neurophysins into three main peptides of differing electrophoretic mobility. Antisera raised in rabbits recognized a common antigenic site in the three peptides and identical radioimmunoassay standard curves were obtained with each of the isolated rat neurophysins. A homologous rat neurophysin radioimmunoassay was utilized to measure neurophysin in samples of unextracted rat plasma. Basal neurophysin levels, 3.7 +/- 0.2 ng/ml (mean +/- SEM), did not differ in samples collected by decapitation, carotid artery cannulation, or tail vein bleeding. Water-loading caused a significant reduction in neurophysin, 2.8 +/- 0.1 ng/ml, while hypertonic saline and dehydration caused a significant elevation, 10.4 +/- 2.1 and 8.0 +/- 1.4 ng/ml, respectively. A step-wise decrease in blood volume caused a step-wise increase in plasma neurophysin concentrations which returned to baseline with reinfusion of the withdrawn blood. A second hemorrhage caused an even greater release of neurophysin indicating large neurophysin reserve in the pituitary. In periodic tail vein samples over 23 days of pregnancy a rise in plasma neurophysin was found from day 14 continuing to parturition with a peak value of greater than 13 ng/ml by day 21. Two days postpartum the value was 4.6 +/- 0.3 ng/ml. With this homologous assay, the basal levels of plasma neurophysin are lower and the stimulated values higher than with previously reported heterologous assays. Therefore, the relative change with physiologic maneuvers is distinctly increased.
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Two human neurophysins, nicotine stimulated neurophysin (NSN), and estrogen stimulated neurophysin (ESN) were assayed during physiologic maneuvers and pathologic states in man. NSN is thought to be associated with vasopressin and was elevated in some subjects by volume depletion, surgical stress, hypotension and hypertonic saline infusion. Overnight dehydration did not elevate NSN in spite of urinary concentration. NSN was elevated in some subjects with the syndrome of inappropriate secretion of antidiuretic hormone and when tested was unresponsive to administered water, alcohol or nicotine. ESN was elevated during estrogen administration, in pregnancy, in newborns and in patients with cirrhosis. NSN was also acutely increased at parturition. These data support the association of NSN with vasopressin although changes in NSN were found only with potent stimuli for vasopressin release. ESN may be associated with oxytocin but demonstration of this awaits knowledge of oxytocin physiology in humans.