Biomedical subjects
Publications and source records attributed to C Oliver.
alpha-MSH secretion was significantly lowered in Rats after lesion of the mediobasal hypothalamus with microinjections of kainic acid. beta-Endorphin release after ether-stress was also reduced. In opposition, no significant change in basal and ether-stress ACTH secretion was observed.
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The vasopressin-producing neurons of the hypothalamo-neurohypophysial system are a particularly good model with which to consider the relationship between the Golgi apparatus nd GERL and their roles in secretory granule production because these neurons increase their synthesis and secretion of vasopressin in response to hyperosmotic stress. Enzyme cytochemical techniques for acid phosphatase (AcPase) and thiamine pyrophosphatase (TPPase) activities were used to distinguish GERL from the Golgi apparatus in cell bodies of the supraoptic nucleus from normal mice, mice hyperosmotically stressed by drinking 2% salt water, and mice allowed to recover for 5-10 d from hyperosmotic stress. In nonincubated preparations of control supraoptic perikarya, immature secretory granules at the trans face of the Golgi apparatus were frequently attached to a narrow, smooth membrane cisterna identified as GERL. Secretory granules were occasionally seen attached to Golgi saccules. TPPase activity was present in one or two of the trans Golgi saccules; AcPase activity appeared in GERL and attached immature secretory granules, rarely in the trans Golgi saccules, and in secondary lysosomes. As a result of hyperosmotic stress, the Golgi apparatus hypertrophied, and secretory granules formed from all Golgi saccules and GERL. Little or no AcPase activity could be demonstrated in GERL, whereas all Golgi saccules and GERL-like cisternae were TPPase positive. During recovery, AcPase activity in GERL returned to normal; however, the elevated TPPase activity and secretory granule formation seen in GERL-like cisternae and all Golgi saccules during hyperosmotic stress persisted. These results suggest that under normal conditions GERL is the predominant site for the secretory granule formation, but during hyperosmotic stress, the Golgi saccules assume increased importance in this function. The observed cytochemical modulations in Golgi saccules and GERL suggest that GERL is structurally and functionally related to the Golgi saccules.
Plasma alpha-MSH, beta-endorphin and ACTH were measured at 60 days of age in rats which had been injected during the neonatal period with monosodium glutamate (MSG). Although the arcuate nucleus tuberoinfundibular dopaminergic and cholinergic system was lesioned by the MSG, no change in circulating alpha-MSH, ACTH and corticosterone levels was observed under basal conditions, after ether stress of adrenalectomy. In contrast, a moderate, but significant decrease in plasma beta-endorphin was noticed after MSG treatment.
Two hours after the ip administration of TRH antiserum, no change in serum TSH concentration was observed in the rat from birth through day 5 of life. Under the same conditions, a significant reduction in serum TSH was observed in 7- to 14-day-old rats. Similarly, in neonatal hypothyroidism, TSH levels did not change in 1-day-old rats, whereas a significant decrease was observed on day 7. The administration of synthetic TRH during the neonatal period induced a significant increase of serum TSH in the newborn; however, TSH release by the pituitary gland increased progressively from days 3-10. Immunoreactive TRH was undetectable in the serum of newborn rats. Adult levels were reached when the rats were 10 days old. It is concluded that neonatal pituitary-thyroid function in the rat is not physiologically dependent upon TRH secretion, although synthetic TRH is able to stimulate the secretion of TSH at birth.
Mecinarone (18.25 mg/kg twice a day orally for 6 months) induces an increase in melanin content of pigmented skin and mucosae in the Beagle dog. This effect is reversible. This effect is not due to a central or an endocrine mechanism because plasma levels of M.S.H., A.C.T.H. and cortisol remain normal. High levels of Mecinarone are found in melanized areas (skin, hair and non tapetal area of the eye). This effect is reversible. In contrast wih the Beagle, studies in pigmented guinea-pig and rabbit have been negative.
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We described potential interference of procainamide with our high pressure liquid chromatography procedure for assaying theophylline (similar to that given by Orcutt et al.). In participating in the AACC-TDM quality-control program, we discovered procainamide interference on a column dedicated to theophylline and acetaminophen serum analyses. Following attempts at rejuvenation, this 7-month-old column was replaced with a new one, which gave base-line separation of theophylline and procainamide with no difficulty. We recommend close attention to the aging characteristics of columns and participation in a quality-control program.
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Neurosecretory neurons of the hyperosmotically stressed hypothalamo-neurohypophysial system have been a useful model with which to demonstrate interrelationships among perikaryal lysosomes, agranular reticulum-like cisterns, endocytotic vacuoles, and the axoplasmic transport of acid hydrolases and horseradish peroxidase. Supraoptic neurons from normal mice and mice given 2% salt water to drink for 5--8 days have been studied using enzyme cytochemical techniques for peroxidase and lysosomal acid hydrolases. Peroxidase-labeling of these neurons was accomplished by intravenous injection or cerebral ventriculocisternal perfusion of the protein as previously reported (Broadwell and Brightman, '79). Compared to normal controls, supraoptic cell bodies from hyperosmotically stimulated mice contained elevated concentrations of peroxidase-labeled dense bodies demonstrated to be secondary lysosomes and acid hydrolase-positive and peroxidase-positive cisterns either attached or unattached to secondary lysosomes. These cisterns were smooth-surfaced and 400--1,000 A wide. Their morphology was similar to that of the agranular reticulum. Some of the cisterns contained both peroxidase and acid hydrolase activities. The cisterns probably represent an elongated form of lysosome and, therefore, are not elements of the agranular reticulum per se. By virtue of their direct connections with perikaryal secondary lysosomes, these cisterns may provide the route by which acid hydrolases and exogenous macromolecules can leave perikaryal secondary lysosomes for anterograde flow down the axon. Very few smooth-surfaced cisterns were involved in the retrograde transport of peroxidase within pituitary stalk axons from normal and salt-treated mice injected intravenously with peroxidase. Peroxidase undergoing retrograde transport was predominantly in endocytotic structures such as vacuoles and cup-shaped organelles, which deliver this exogenous macromolecule directly to secondary lysosomes for degradation in the cell body. These observations extend our previously reported findings in the axon to the cell body and suggest that agranular reticulum-like cisterns in the perikaryon, like those in the axon, may be part of the lysosomal system rather than associated with the agranular reticulum. A diagram summarizing the lysosomal system of organelles and proposed transport of acid hydrolases and peroxidase in neurosecretory neurons specifically and in neurons in general is provided.
The injection of haloperidol, a dopamine receptor blocker, was followed by a large increase of plasma ACTH and beta-endorphin-like immunoreactivity (beta-EI) in the rat. This effect was prevented when the rats were previously treated with corticosteroids. These results suggest that catecholamines inhibit ACTH and beta-endorphin secretion in the rat.
The present electron microscopic cytochemical investigation was undertaken to characterize the alterations in the golgi apparatus and GERL of rat parotid acinar cells during ethionine intoxication and recovery. Although the Golgi apparatus and GERL were reduced in size, and some broadening of the Golgi saccules occurred as the result of ethionine treatment, the relative localization of thiamine pyrophosphatase (TPPase) activity in the Golgi saccules, and acid phosphatase activity (AcPase) in GERL, remained unchanged. Shortly after ethionine treatment was stopped, a dramatic redistribution of enzyme activities was noted. Within the first 24 hours of recovery, the Golgi apparatus began to enlarge, and the content of secretory granules increased. By day 3 of recovery, cisternae morphologically identifiable as GERL and forming secretory granules possessed TPPase activity, while AcPase activity was virtually undetectable. After seven days of recovery, the Golgi apparatus and GERL appeared both morphologically and cytochemically normal. The enzyme modulation observed during recovery may be correlated with increased secretory granule production. Furthermore, the presence of TPPase activity in GERL and forming secretory granules lends support to the suggestion that GERL may be derived from the trans Golgi saccule.
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Methods have been developed for isolating and maintaining differentiated rat exorbital lacrimal, parotid, and pancreatic acinar cells for up to 1 month in culture. The dissociated cells retained their differentiated morphology when cultured as suspension cultures at 35 degrees C with the appropriate secretagogue (exorbital lacrimal, 10(-6) M carbamyl choline; pancreas, 10(-5) M carbamyl choline; parotid, 10(-6) M isoproterenol). Under these conditions the cells remained viable and differentiated for up to 4 weeks in culture and continued to incorporate 3H-leucine at rates similar to those of freshly isolated cells. If secretagogue was omitted from the medium, the cells rapidly degenerated. These results indicate that differentiated exocrine gland acinar cells may be maintained in vitro and utilized as a model system for the study of secretory processes.
beta-Endorphin-like immunoreactivity (beta-ELI) was measured in hypophysial portal and arterial blood of intact, adrenalectomized and hypophysectomized rats. beta-ELI levels were 61 times higher in the long portal vessels than in the general circulation. Circulating, and especially portal, levels of beta-ELI were significantly increased after adrenalectomy. After removal of the pituitary gland, the mean level of beta-ELI in portal blood was significantly lower than in intact rats. beta-ELI in portal blood displayed the same chromatographic properties as synthetic beta-endorphin.
The hypothalamic regulation of ACTH secretion has been reviewed. Recent biochemical investigations on corticotropin-releasing factor (CRF) suggest that CRF is present in the hypothalamus under two or more different molecular weight forms, their structure being not elucidated yet. Vasopressin has a CRF-like activity. However, contradictory results have been reported on the role of AVP as a physiological CRF. The synthesis of CRF appears to occur in a large hypothalamic area outside the median eminence. CRF-carrying fibers are thought to pass through the lateral retrochiasmatic area and project on the hypophysial portal vessels at the junction between the pituitary stalk and the median eminence. Conflicting data have been published on the influence of monoamines on ACTH secretion. In the dog, ACTH release is inhibited by the alpha-adrenergic receptors, this effect being not as clearly demonstrated in other species. The stimulation of nicotinic and muscarinic receptors followed by increased ACTH secretion. Glucocorticoids appear to lower ACTH secretion through an action at both the hypothalamic and pituitary levels.
The immunologic patterns of 3 human pituitary adenomas of Cushing's disease have been studied after gel exclusion chromatography (Sephadex G-50). The immunologic characteristics were examined with three radioimmunoassays specific for human corticotropin (ACTH), lipotropin (LPH) and beta-endorphin (beta-End). In cell tumor extracts, chromatographic peaks corresponding to beta-LPH, gamma-LPH, beta-End and ACTH were identified. The ACTH/beta-LP-beta-End ratio was 1 in the 3 cases. Additionally, in the 3 cases, a chromatographic peak, partially cross-reacting in the beta-End assay, was eluted after beta-End, thus suggesting the presence of a fragment of the molecule. In 1 case, a peak of large molecular weight material with N- and C-terminal beta-LPH and ACTH immunoreactivity was observed, which corresponded to the precursor material. The release and the effects of various stimuli were studied on dispersed tumor cells in primary culture. The tumor cells had a biphasic basal secretion rate with a rapid increase of ACTH/beta-LPH-beta-End in the culture medium during the first 2 h. Then the release, studied during 2 days, was slower. Chromatographic studies showed that the beta-LPH/beta-End ratio was 0.8 in the cells and 0.3 in the medium, due essentially to the release of beta-End and beta-End-like materials. The cells released ACTH and beta-LPH-beta-End in equimolar ratio after stimulation with arginine vasopressin (AVP). The maximum effect was obtained with 10(-6) M AVP (D50 = 1 10(-9) M). Dibutyryl cyclic AMP (2. 10(-3) M) induced maximal release of ACTH/beta-LPH-beta-End. This stimulation was suppressed by a 48-hour preincubation with dexamethasone (10(-8)-10(-6) M). There was no effect of TRH and LH-RH on cell release. Dopamine (10(-6) M) specifically blocked the release of ACTH/beta-LPH-beta-End in 1 case. These data showed (a) heterogeneity of chromatographic profiles from case to case; (b) the presence of material in the tumor, cell extracts and culture medium corresponding to fragment(s) of beta-End; (c) culture studies demonstrated that tumor cells remain responsive to AVP stimulation and dexamethasone suppression, and (d) the dopamine inhibition of ACTH and beta-End release needs further investigation.