Human placental 17 beta-hydroxysteroid dehydrogenase is homologous to NodG protein of Rhizobium meliloti

The amino acid sequence of human placental 17 beta-hydroxysteroid dehydrogenase (17 beta-OH-steroid dehydrogenase) was found to be similar to that of the NodG protein of Rhizobium meliloti. The computer-based comparison score is 11.5 SD higher than that obtained with 2500 comparisons of randomized sequences of these proteins. The probability of getting such a score by chance is 6 x 10(-31). 17 beta-OH-steroid dehydrogenase is also similar to Klebsiella aerogenes ribitol dehydrogenase and Escherichia coli glucitol-6-phosphate dehydrogenase. We propose that the steroid recognition site on 17 beta-OH-steroid dehydrogenase evolved from an ancestral recognition site for polyols such as ribitol and glucitol-6-phosphate.     

Functional morphology of the adrenal cortex during the physiological rhythm of sex steroid synthesis]

A method of a quantitative histenzymological analysis was used for determination of the extent of participation of various zones of the adrenal cortex in provision of physiological rhythm of the steroid synthesis. The activity of 3beta-OH-steroid dehydrogenase, glucoso-6-phosphat dehydrogenase, NAD- and NADP-diaphorases, acid and alkaline phosphatases and non-specific esterase was investigated. The data of a histoenzymotological study were compared with the result of biochemical analysis of corticosteroids in the peripheral blood. Under physiological conditions intensification of steroidogenesis was realized by mobilization of individual groups of cells of the adrenal gland, not its whole parenchyma. Physiological rhythm of steroid synthesis was provided by an integrated function of all the zones; however, by duration and quantitative expression of the secretory activity a structural heterogeneity was revealed in the adrenal cortex.     

Histological development of the equine fetal adrenal gland.

The horse fetal adrenal gland was shown to begin to increase in weight from about the end of the 4th month of pregnancy when the fetus has a crown-rump length of about 20 cm. Growth then proceeds steadily to term but, in contrast to the adult horse, the medulla remains thicker than the cortex throughout fetal life. The cortex also becomes established around 20 cm crown-rump length and at the same time the glomerular and fascicular zones become distinguishable. In contrast the reticular zone is not differentiated until around 50 cm crown-rump length. In the fetal adrenal cortex, the fascicular zone is less prominent than in the adult horse although counts of cell nuclei in the cortical region indicate hypertrophy of the fascicular cells during the last third of gestation.     

Sex differences in adrenocortical structure and function. XI

Summary Adrenal glands from orchectomized and ovariectomized rats, with and without replacement therapy, and also from intact controls of both sexes, were examined by autoradiography with ³H-thymidine. The labelling index after 1 or 2 nucleoside injections was higher in the zona glomerulosa of females than in male rats, while no differences were found in the fascicular and reticular zones. Orchiectomy increased the labelling index in the fascicular and reticular zones, an effect prevented by testosterone. Ovariectomy did not change the labelling index, while estradiol lowered it in the zona glomerulosa. Duration of the S phase was longer in the zona fasciculata cells of males than in females. Both orchiectomy and testosterone shortened this phase in cells of the zona fasciculata and zona reticularis. Ovariectomy prolonged the S phase in the zona fasciculata and shortened this time in the reticular zone, an effect reversed by estradiol.In the glomerular and fascicular zones, cell cycle time was longer in males than in females. Orchiectomy shortened this time in all adrenocortical zones, an effect reversed by testosterone. Ovariectomy shortened cell cycle time in the glomerular and reticular zones and prolonged it in the zona fasciculata; these effects were reversed by estradiol. Turnover rate in adrenocortical cells was markedly higher in females than in males, a difference due to testosterone which markedly decreased turnover rate.     

Changes in the combined activity of the thyroid and the fascicular zone of the adrenal cortical substance in the development of subcutaneous connective tissue inflammation during prolactin administration

As demonstrate the experiments performed in white male rats, during development of an inflammatory reaction, some essential fluctuations take place in nicotinamide dinucleotide. H2 (HAD.H2), nicotinamide dinucleotide phosphate. H2 (NADPh.H2), glucose-6-phosphate-dehydrogenase (G-6-PhDH), monoaminoxydase (MAO) activities and in content of ascorbic acid in the fascicular zone of the adrenals and the same enzymes in the thyroid follicular cells. There is a reverse connection between the adrenal fascicular zone and the thyroid gland activity. At inflammation, prolactin increases MAO and G-6-PhDH activity in thyrocytes and adrenocorticocytes of the adrenal fascicular zone, changes correlation between NAD.H2-DG and NADPh.H2-DG activities. At an acute inflammation, prolactin activates the thyroid gland function, and during the reparative period--decreases it. During the inflammation period, prolactin administration decreases contingency of the indices in the thyroid gland-adrenals systems, that is to say produces a dissociative effect; it is, perhaps, connected with certain changes in balance and a mediatory role of biogenic amines.     

Functional relations of the adrenal cortex, thyroid and pineal body. II. Adrenal cortex reaction following epiphysectomy and administration of melatonin

Histologic-cytological and morphometrical changes were investigated in the adrenal cortex of male Wistar-rats following pinealectomy and application of melatonin in eu-, hypo-, and hyperthyroid situations. A rat experiment (at an average of 45 d) to find a possible functional connection between the pineal gland and the adrenal cortex was carried out. In the literature, there are only a few of informations about the role of the pineal in regulating ACTH secretion. The results are very contrarily. We found that pinealectomy is connected with a progressive transformation and melatonin with a little regressive transformation in the adrenal cortex. But, it is not evident, that the glomerular zone is activated after both pinealectomy and application of melatonin. In our opinion, the glomerular zone and the secretion of aldosterone increased after as well pinealectomy as melatonin. Application of melatonin diminishes the function of the pineal gland (see group 4-pinealectomy plus melatonin-where was found a progressive transformation). Under these experimental conditions, one can speak of a "pharmacological pinealectomy" after application of melatonin alone. However, the effect of melatonin on the fascicular zone and the glomerular zone is different. The effects of pinealectomy or application of melatonin in combination with methylthiouracil or thyroxin are relatively unimportant.     

Functional interrelationships of the sympathetic nervous system and the hypothalamo-hypophyseo-adrenal complex]

Adrenal and hypothalamic structure has been studied in mice at functional inhibition of the sympathetic region of the vegetative nerve system by means of antibodies against the nerve growth factor. Routine histological, histochemical, morphometric, electron microscopic and radioautographic methods have been applied. In the experiment the hypothalamic region is in the state of a continuous functional stress which is evident from enlargement of neurons and their nuclei in the macrocellular neurosecretory nuclei of the hypothalamus. The method of radioautography proves increasing activity in synthetic processes taking place in supraoptic, paraventricular and ventromedial nuclei of the hypothalamus and in the medial habenular nucleus of the epithalamus. In 30-day-old mice certain structural changes have been revealed in the adrenals demonstrating an increasing activity in their cortex: blood vessels are dilated, cholesterine, lipid and ascorbic acid granules are not evenly distributed, enzymatic activity in cytoplasm of adrenocorticocytes is increased. Ultramicroscopic destructive and regenerative alterations have no definite zonal specificity, nevertheless they are more pronounced in the fascicular zone. Radioautographic and morphometric investigations demonstrate an increasing functional activity in glomerular and fascicular adrenal zones. Taking into account morphologic demonstration of functional stress in hypophysial adenocytes in the same animals (Molostov O. K., 1974), it is possible to conclude that lesions in the sympathetic system center result in adaptive reaction of the hypothalamo-hypophysial system which, in its turn, produces reactions in the adrenals and in the vascular complex. This interconnection is accompanied by the reaction depending on breaking off direct sympathetic effects in the adrenals and vessels.     

Morphofunctional status of the adrenal cortex in female silver foxes and the effect of domestication and photoperiodic conditions

Studies on 7-day-old and 8-month-old female silver foxes indicate that additional photostimulation affects to a various extent morphological and functional condition of the adrenal cortex in animals selected and unselected for the domestication type of behaviour. In relatively wild foxes, additional illumination stimulated the activity of the reticular zone, whereas in domesticated animals the same photoperiod increased the activity in the fascicular zone. It is suggested that selection of silver foxes for the domestication type of behaviour affects the sensitivity of the adrenals to external illumination.     

The ultrastructural localization of membrane ATPase in rat thin limbs of the loop of Henle

Summary Intraacinar distribution of succinate dehydrogenase (SDH), malate dehydrogenase (MDH), NADP-dependent isocitrate dehydrogenase (IDH), glutamate dehydrogenase (GluDH), lactate dehydrogenase (LDH) and NADH-tetrazolium dehydrogenase (TR) was studied in rat liver cryostat sections by multipositional microphotometric activity determinations. By statistical evaluation, activity of individual enzymes could be related to the acinar topography. Activity was evaluated with regard to distance of measuring position either from afferent (portal) or efferent (hepatic) vessels. Two independent distribution curves were obtained for each enzyme. Acinar distribution of all the enzymes studied followed sigmoid courses with maximal activity of SDH, MDH and LDH in zone 1 (periportal) and GluDH, IDH, TR in zone 3 (pericentral). For all enzymes, maximum activity gradients were confined to zone 2 of the acinus. Data were also evaluated as ratios of activities in zone 1 and zone 3. The following ratios zone 1/zone 3 were obtained: SDH=1.9, MDH=1.7, IDH=0.5, GluDH=0.5, LDH=1.3 and TR=0.6.     

Ultrastructure of the zone fascicularis of the adrenal cortex of the rat after a single physical loading to fatigue and in the recovery period

Ultrastructure of the fascicular zone in the cortex of the adrenals has been studied in untrained rats after a single physical loading (swimming with an additional load up to fatigue) and during restorative period (24, 48, 72 and 96 h of rest after the loading). The massive release of hormones during the prolonged physical work, as well as during the 1st and the 3d days of rest are estimated by ultrastructural changes in adrenocorticocytes. Signs of an increased permiability of the histohematic barrier in the gland are mostly manifested in 48 h after the loading: in the wall of the smallest vessels ruptures and discharge of formed elements of blood into the pericapillary space; numerous macrophages in the intercellular space phagocytaze the products of degeneration; residual bodies, fragments of decaying cells are seen in the blood capillary lumen. In 96 h of rest, in the fascicular zone of the adrenal cortex changes directed to restoration of the cholesterin depot are observed.     

NADP-dependent dehydrogenases in rat liver parenchyma

Summary The activities of glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6PGDH), malic enzyme (ME) and isocitrate dehydrogenase (ICDH) were investigated with optimized histochemical methods (Rieder et al. 1978), and the activity of 3-hydroxybutyrate dehydrogenase (3HBDH) and neutral fat content with conventional techniques in the liver of male rats under the following experimental dietary conditions: (A) Fasting for 0, 12 and 84 h; (B) 84-h fasting followed by refeeding with a low-fat, high-carbohydrate diet for 6 h and for 2, 3, 5, 7, 11 and 14 nights; (C) refeeding with standard diet for 5 nights; (D) low-fat, high-carbohydrate diet for 7 and 14 nights.The activities of G6PDH, 6PGDH and ME decreased slightly during fasting primarily in zone 1 and increased dramatically on refeeding with a low-fat, high-carbohydrate diet. This activity increase was confined mainly to zone 3 during the first 3 days and was accompanied by a deposition of neutral fats that began in zone 3 and progressed to zone 1. Neutral fat accumulation was maximal after 3 nights, with a uniform accumulation of large droplets in all the hepatocytes; this was followed by a release that started in zone 3 and proceeded in a periportal direction. On the other hand, G6PDH, 6PGDH and ME attained their maximum activities after 5 and 7 nights of the low-fat diet, the activities being nearly homogeneously distributed over the liver acinus in a few cases. Subsequently the activities fell mainly in zone 1, causing the activity patterns and levels to approach those of the animals in group (D). In contrast to this, the activity of ICDH increased during fasting principally in zone 1, so that the otherwise steep activity gradient in favor of zone 3 lessened. Refeeding led at first to a fall of activity below the initial value, but later the normal distribution pattern was restored. The activity of 3HBDH showed a behavior similar to that of ICDH. The findings are discussed with reference to the functional heterogeneity of the liver perenchyma, and the existence of a liponeogenic area in zone 3 is proposed.Essential parts of this study have been presented to the Medical Faculty of the University of Freiburg/Br. as an inaugural dissertationSupported by grants from the Deutsche Forschungsgemeinschaft (Sa 127/7) and SFB 46     

Age and the effect of adrenocorticotropic hormone on aldosterone secretion in rats

Age-related changes in functional activity of the glomerular zone were studied in the adrenal cortex of Wistar rats. It was shown that secretion of the basic mineralocorticoid hormone aldosterone was decreased with age. The glomerular zone of old rats showed the reduced sensitivity to the stimulant action of corticotropin, marked by the pronounced reaction to less doses of the hormone administered. At the same time the reactivity and the range of shifts in the course of ACTH dosage build-up decrease with aging.     

Biosynthesis of corticosteroid hormones in the cortical areas of the rat adrenal during emotional stress combined with a salt load

The experiments on male albino rats have shown that excessive salt uptake increases the functional sensitivity of the adrenal cortex to emotional stress (group fighting). Emotional stress in combination with a salt load induces a much greater increment in corticosterone and 18-oxy-11-deoxycorticosterone production by fascicular and glomerular adrenal zones through the activation of the pregnenolone pathway of hormonal biosynthesis. A relatively high aldosterone production was also retained. Thus, the total mineralocorticoid potential directed to sodium retention in the body is in these conditions inadequately increased.     

Predilection of Segmental Glomerulosclerosis Lesions for the Glomerulotubular Junction Area in Type 1 Diabetic Patients: A Novel Mapping Method

The location of segmental glomerular lesions in relation to the vascular or tubular pole may have diagnostic or prognostic significance. We have developed a model-based method to estimate the distance from a glomerular lesion to a given landmark (vascular or tubular pole) or the glomerular center and applied this to biopsies from 5 microalbuminuric, 5 normoalbuminuric and 7 proteinuric type 1 diabetic patients and 5 normal controls. The distance from each glomerular adhesion to the glomerulotubular junction was measured and divided by the glomerular radius, allowing comparability among different glomeruli, assuming a spherical shape for Bowman''s capsule, an assumption which was validated. The frequency of adhesions in 6 glomerular zones with equal height (zone I adjacent to the glomerulotubular junction and zones II–VI progressively farther away) was determined: 59% of adhesions were in zone I, 15% in zone II, 16% in zone III, 7% in zone IV and 3% in zone VI (adjacent to the hilus). In glomeruli with only one adhesion, 82% of these were in zone I. This new method accurately localizes segmental lesions within glomeruli and revealed a marked predilection in type 1 diabetic patients for segmental sclerosis to develop at the glomerulotubular junction.     

Histochemical studies on metabolic zonation of the liver in the trout (Salmo gairdneri)

The livers of 26 adult male and female trout were studied histochemically. G6Pase activity was always found to be heterotopically distributed with a constant maximum in the periportal area. In many cases the glycogen content and the activity of phosphorylase predominated in the periportal zone as well. Maximum activity of glucose-6-phosphate-dehydrogenase and malic enzyme, however, could be demonstrated preferentially in the perivenous area. Lactate dehydrogenase, succinate dehydrogenase, alcohol dehydrogenase, acid phosphatase and beta-glucuronidase were found equally in all liver cells. 3-Hydroxybutyrate dehydrogenase was absent. Thus, the principles of metabolic zonation have been established in trout liver, the architecture of which differs essentially from that of mammals. The course of the terminal afferent and efferent vessels is the decisive factor for the heterotopic localization of functional units rather than the tubular or plate-forming arrangement of the hepatocytes.     

Fine structure of trypsin-dissociated rat adrenal cells

Summary Electron micrographs of trypsin-dissociated rat adrenal showed predominantly intact rounded cells without internal damage. The population contained cells from the glomerular, intermediary and fascicular zones with cells from the zona fasciculata predominant. The presence or absence of cells from the reticular zone could not be determined. Cells from the medullary zone were absent. The addition of adrenocorticotropic hormone (ACTH) to the cellular suspension for 2 hours produced corticosterone. However, these stimulated cells did not display any significant ultrastructural change.Supported by research grants from the U.S.P.H.S. (No. GM15872), and the Research Council of Rutgers University, and the National Science Foundation (No. GB7427 to Dr. George Sayers). We are indebted to Mrs. Jean A. Gibney, Miss Rose-Marie Ma, and Mrs. Mary Vegh for their excellent technical assistance.Postdoctoral Trainee, U.S.P.H.S. Training Grant No. 5T01-GM00899-11.     

Adaptive reactions of dehydrogenation processes in root voles during additional impacts of the physical nature

Variations of the dehydrogenation enzyme activity (succinate dehydrogenase, pyruvate dehydrogenase, lactate dehydrogenase) in the heart muscle, liver and brain of root voles (Microtus oeconomus Pall.) and their progeny associated with additional stress effects (chronic low-level gamma-irradiation, short-term exposure to cold) have been studied. Root voles (parents) were caught in the areas with a normal and high-level natural radioactivity in the Republic of Komi. It has been revealed that the direction of shifts of the dehydrogenation enzyme activity in response to the factors of the physical nature is determined by the initial level of the oxidation process in tissues of root voles and their progeny that haven't been subjected to these actions. The reaction of root voles and their progeny (1-3 generations) from the radium zone has lower reserve functional possibilities in relation to the additional exposure as compared with the animals from the control zone. In some cases, chronic low-level irradiation and short-term cooling lead to leveling of differences between groups of animals which initially varied from each other in biochemical indexes.     

Changes in hepatocyte dehydrogenase activity in different zones of liver acini during the revascularization of ischemic extremities

After ischemia (3, 6, 9 and 12 h) of the hind extremities in dogs with a subsequent revascularization for 2 h, enzymatic activity of hepatocytes changes. After ischemia for 3 h the enzymatic activity increases. Restoration of the blood flow at later stages of the experiment results in a progressive decrease of dehydrogenase and diaphorase activities. To a greater extend the changes of the enzymatic activity are observed in perivenular hepatocytes (in the 3d zone of the hepatic acinus).     

Biochemical quantitation and histochemical localization of glucose-6-phosphate dehydrogenase activity in the olfactory system of adult and aged rats

The activity of glucose-6-phosphate dehydrogenase, the rate-limiting enzyme of the hexose monophosphate shunt, was examined in olfactory epithelium, respiratory epithelium, olfactory bulb, and occipital cortex in Fisher 344 rats aged 4 and 24 months. Marked differences in this enzyme were found in olfactory compared to nonolfactory tissues. Olfactory epithelium and olfactory bulb have much greater glucose-6-phosphate dehydrogenase activity than respiratory epithelium and occipital cortex at both ages. Glucose-6-phosphate dehydrogenase remains fairly constant between adulthood and senescence in respiratory epithelium and occipital cortex. However, glucose-6-phosphate dehydrogenase activity decreases during the same time in both of the olfactory tissues examined. Previous studies of changes in this enzyme with aging have shown increases in enzyme activity in some brain regions, but never the decreases that we describe in olfactory tissues. Glucose-6-phosphate dehydrogenase histochemistry revealed intense staining of both the apical layer of olfactory epithelium and of Bowman's glands along with their ducts. Histochemistry of the olfactory bulb showed strongest staining in the nerve and glomerular layers of the bulb. The functional implications of these findings are discussed.     

Catheter ablation of fascicular ventricular tachycardia

Fascicular ventricular tachycardia (VT) is an idiopathic VT with right bundle branch block morphology and left-axis deviation occuring predominantly in young males. Fascicular tachycardia has been classified into three subtypes namely, left posterior fascicular VT, left anterior fascicular VT and upper septal fascicular VT. The mechanism of this tachycardia is believed to be localized reentry close to the fascicle of the left bundle branch. The reentrant circuit is composed of a verapamil sensitive zone, activated antegradely during tachycardia and the fast conduction Purkinje fibers activated retrogradely during tachycardia recorded as the pre Purkinje and the Purkinje potentials respectively. Catheter ablation is the preferred choice of therapy in patients with fascicular VT. Ablation is carried out during tachycardia, using conventional mapping techniques in majority of the patients, while three dimensional mapping and sinus rhythm ablation is reserved for patients with nonmappable tachycardia.