[The possibility of a pathogenetic interpretation of keloids in relation to adrenal cortex alterations; clinical case report].
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The ability of different lipoprotein Lp[a] preparations to compete with LDL-binding to the B/E-receptor was investigated by ligand blot and filter assays. Lp[a] was purified from donors with various genetic polymorphic forms by affinity chromatography using lysine-Sepharose or specific immunoadsorbers. These preparations were free of "LDL-like" material. Part of Lp[a] was reduced and freed from specific apo[a] antigen yielding "Lpa-." 125I-labeled low density lipoproteins (LDL) were incubated with B/E-receptor preparations from bovine adrenal cortex or from human skin fibroblasts, and the competition with unlabeled LDL, Lp[a], Lpa-, apo[a], and apoE-free HDL was studied by a ligand blot or filter assay technique. The following results were obtained. 1) LDL and Lpa- were equally potent in displacing 125I-labeled from B/E-receptor in the ligand blot and the filter assay. Lpa + ( = Lp[a]) also displaced LDL but to a much lesser degree: 50% displacement was observed with LDL and Lpa- at a 1-fold excess, whereas a 7.5-fold excess was required of Lpa +. 2) Apo[a], as well as apoE-free HDL, did not compete with LDL binding. 3) Competition experiments using B/E-receptors from bovine adrenal cortex or from human skin fibroblasts were comparable. 4) There was no difference in the behavior of Lp[a] isolated from the two affinity chromatography methods. 5) Lp[a] of different genetic variants behaved virtually identically. The results are discussed from the point of view of the in vivo metabolism of Lp[a].
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Morphometric, histochemical and biochemical methods were used to study the adrenal cortex of rabbits given cholesterol over 60 days' period and killed 5.5 months after the treatment was discontinued. Cholesterol-induced changes were found to undergo considerable regression 5.5 months after the treatment withdrawal.
ACTH elongates the half-life of the mitochondrial proteins from the rat adrenal cortex, and chloramphenicol inhibits this effect of ACTH. The hypothesis is advanced that the ACTH-provoked stabilization of the adrenocortical mitochondrial proteins requires continuous mitochondrial DNA-dependent protein synthesis.
Possibilities of computer tomography (CT) application for differential diagnosis of tumors of the adrenal cortex (TAC) were studied. CT was conducted in 157 patients with TAC, including 75--with malignant (MTAC), 82--with benign (BTAC), permitting to revealed MTAC in 76% patients. In 17.1% patients with BTAC false-positive results were noted, reducing, thus, the method diagnostic value. While the trustworthy signs of malignancy are absent, it is necessary to conduct morphological verification of the adrenal tumors nature using puncture biopsy and/or intraoperative express-cytological investigation.
5-Bromo-2'-deoxyuridine (BrdU) has been recently found to enhance adrenal glucocorticoid secretion in rats. Since BrdU-labeling is today the most employed technique for assessing cell proliferation, we have investigated whether this side-effect of BrdU may influence mitotic activity (as evaluated by metaphase-arrested cell counting) in the thymus cortex and regenerating adrenal cortex. BrdU (1 mg/100 g body weight) evoked a 6-fold rise in the blood level of corticosterone in intact rats, but not in animals bearing regenerating adrenals, in which glucocorticoid secretion was very low. Mitotic index in the thymus of intact rats was not changed by BrdU, but it was strongly depressed in regenerating adrenals. These findings rule out the possibility that the glucocorticoid secretagogue action of BrdU exerts a sizable effect on the proliferative activity of both thymus and adrenal cortex. The marked lowering in the mitotic rate in the regenerating adrenal cortices could be ascribed to the well-know differentiation promoting action of BrdU, a finding which, if confirmed, would make highly unreliable the use of BrdU-labeling technique in cultures of adrenocortical cells.
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The effect of Mg2, ATP and some of its analogs was studied on the spontaneously active and the ATP-Mg-dependent forms of phosphorylase phosphatase extracted from adrenal cortex. Inhibition of the spontaneously active form was observed with Mg2 (Ki - 9mM), ATP (Ki = 9micronM), 2'-doxy-ATP (Ki = 8 micronM), AtetraP (Ki = 9 micronM), AMP(CH2)PP (Ki = 11 micronM), ADP(CH2)P (Ki = 19 micronM), ADP(NH)P (Ki = 16micronM) and ADP (Ki = 25micronM). Activation of the ATP-Mg-dependent form was obtained with Mg2 (Ka = 0.55mM) (to a lower extent) and with ATP (Ka = 2micronM), 2'-deoxy-ATP (Ka = 6micronM) or AtetraP (Ka = 15micronM) in the presence of 0.5mM Mg2. Activation with AMP(CH2)PP was only observed in the presence of high concentrations (5mM) of Mg2 (Ka = 13micronM). No activation at all was observed with ADP(CH2)P or ADP(NH)P. Even though the activation of the ATP-Mg-dependent form does not seem to involve a kinase reaction, the stimulation by ATP or its analogs is rather specific, since it does not occur with analogs in which a methylene group or a nitrogen is substituted for the oxygen between the beta- and gamma-phosphates.
Functional and morphologic studies of the adrenal cortex and kidney have been carried out in pregnant sheep with spontaneous or dietary restriction-induced ovine toxaemia. It was found that proteinuria was an inconstant feature and no animal showed glomerular lesions analogous to those found in human preeclampsia; thus ovine toxaemia cannot be regarded as a precise experimental model for human toxaemia of pregnancy. The elevation of blood cortisol levels and the morphologic appearance of the adrenal zona fasciculata found in such animals suggest an adrenal response comparable to that caused by adrenocorticotrophic hormone. In addition, animals with severe disease showed evidence of stimulation of the renin-angiotensin-aldosterone system as reflected by elevated blood renin and aldosterone concentrations and raised renal juxtaglomerular indices. Ultrastructural changes in the adrenal zona glomerulosa and renal juxtaglomerular myoepithelioid cells in toxaemic animals resembled those described in non-pregnant sodium-depleted sheep. The finding of juxtaglomerular peripolar cell mitoses and granule exocytosis, the latter only being previously observed in sodium depleted sheep, together with the ultrastructural changes in the adrenal zona glomerulosa and juxtaglomerular myoepithelioid cells, suggest that sodium depletion may play a role in this disease.
Electron-microscopic investigations on two human adrenal gland tumors have been carried out. The glucocorticoid and androgen producing tumor predominantly showed mitochondria similar to those of normal human zona fasciculata and zona reticularis. On the other hand, the non hormone producing tumor failed to imitate typical adrenal gland mitochondria. "Light" and "dark" cells were seen like in the normal adrenal cortex. Although a few liposomes were found in nearly all cells only 6 to 8% of the cells contained liposome numbers comparable to normal adrenal gland. A possible explanation is discussed.
Male mice (19--20 g) were observed to have mitotic peaks in the zona fasciculata of the adrenal cortex during morning hours and in the first half of the day, while high values of nuclear volumes were characteristic of the said mice in the second half of the day and at night. In the zona glomerulosa, the mitotic index was increased in the second half of the day and in the evening hours, and the nuclear volume was greater at night-time.
Alkaline phosphatase activity (AP) of the adrenal cortex of rats were determined under the effect of ethinyl estradiol (EE) and/or norethisterone acetate (NA), the two components of the contraceptive pill gyn-anovlar (Schering AG Berlin). A pathological study was also carried out to examine the effects of EE and NA on other tissues mainly the liver, lungs, spleen and ovaries. EE in a dose of 10 micrograms/day for 2 weeks caused a significant increase in the weight of the adrenal but no significant increase in the AP/g cortical tissue. The 25 and 50 micrograms doses for the same period caused a significant increase in both adrenal weight and AP. When treatment was prolonged to 6 weeks no effect on adrenal weight or AP was detected. The same finding was obtained with NA in a dose of 7 mg/rat/day for 2 weeks. The 14 mg dose of NA for the same period caused a significant increase in adrenal weight but no effect on AP. The 21 mg dose caused a significant increase in adrenal weight accompanied by significant decrease in AP/g cortical tissue. Treatment with NA for 6 weeks caused a rise in adrenal weight and AP with the 7 mg dose, then a decline in AP with the 14 mg dose, and a decline in both adrenal weight and AP with the 21 mg dose. As regards the effects of EE and NA on other tissues, EE was found to have a powerful stimulatory effect on the reticuloendothelial system (RES) as well as toxic effects on the liver. NA did not produce such lesions except for the large doses and prolonged periods of treatment. In addition NA produced cholestasis in the liver associated with staining of the liver cells with bile. Combination of EE and NA in the form of gyn-anovlar produced more powerful stimulation of RES and decreased the toxic manifestations of either component. As regards the ovaries, administration of 50 micrograms EE for 6 weeks produced profound hyperplasia of the granulosa cells of the Graafian follicles and inhibited ovulation, however, NA did not inhibit ovulation. With gyn-anovlar, the effect of EE on the ovaries seemed to predominate and ovulation was inhibited.
Noradrenergic innervation of the human adrenal cortex was investigated using immunohistochemistry directed at dopamine-beta-hydroxylase. Nerves were present as slender trunks and individual varicose fibres in the capsule and all cortical zones except the inner zona reticularis. Some fibres were located adjacent to blood vessels and in the muscular tunics of arterioles; others were apparently adjacent to parenchymal cells. These results in the human confirm and extend previous animal studies and suggest a possible anatomical substrate for regulation of adrenal blood flow, and also for the direct action of noradrenaline on zona fasciculata cells to stimulate glucocorticoid secretion via beta-1-adrenoceptors.
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