The adrenal cortex after estradiol or daidzein application in a rat model of the andropause: Structural and hormonal study.

INTRODUCTION AND AIM: Daidzein application may represent an effective and less harmful alternative to indicated, classical estrogenization of ageing men. The aim of this study was to perform structural and hormonal analysis of the adrenal cortex, after estradiol or daidzein supplementation in a rat model of the andropause. MATERIAL AND METHODS: Middle-aged Wistar rats were divided into sham operated (SO; n = 8), orchidectomized (Orx; n = 8), estradiol treated orchidectomized (Orx + E; n = 8) and daidzein treated orchidectomized (Orx + D; n = 8) groups. Estradiol (0.625 mg/kg b.m./day) or daidzein (30 mg/kg b.m./day) were administered subcutaneously for three weeks, while the SO and Orx groups received the vehicle alone. Set objectives were achieved using stereology, histochemistry/immunohistochemistry, immunoassays and ultrastructural analysis. RESULTS: Both estradiol and daidzein treatment significantly increased volumes of the zona glomerulosa cell and nuclei, but decreased circulating aldosterone levels. Estradiol markedly increased volumes of the zona fasciculata cell and nuclei in parallel with significant decrease of the adrenal tissue level of corticosterone, while daidzein significantly decreased both the adrenal and circulating levels of corticosterone. Serum DHEA level and volumes of the zona reticularis cell and nuclei significantly increased upon estradiol treatment, whereas daidzein even stronger increased the circulating level of DHEA. Shunting of the corticosteroidogenesis pathways towards adrenal androgens production, after the treatments, corresponded to the ultrastructural findings and zonal capillary network rearrangements. CONCLUSIONS: Given the coherence of its effects and relative safety, daidzein could be the remedy of choice for the treatment of ageing-caused androgen deprivation and the hypothalamo-pituitary-adrenal axis hyperfunction/related metabolic issues in males.

Effect of Schisandra chinensis on interleukins, glucose metabolism, and pituitary-adrenal and gonadal axis in rats under strenuous swimming exercise.

OBJECTIVE: To investigate the effect of Chinese medicine (CM) Schisandra chinensis on interleukin (IL), glucose metabolism, and pituitary-adrenal and gonadal axis of rats after strenuous navigation and exercise. METHODS: A total of 45 Sprague-Dawley rats were randomized into the quiet control group, the stress group, and the CM group (15 in each group). The CM group received 2.5 g/kg of Schisandra chinensis twice per day for one week before modeling. Except the quiet controls, rats were trained using the Bedford mode for 10 days. On the 11th day, they performed 3 h of stressful experimental navigation and 3 h of strenuous treadmill exercise. The levels of serum testosterone (T), cortisol (CORT), luteinizing hormone (LH), IL-1, IL-2, and IL-6 were tested by radioimmunoassay and enzyme-linked immunosorbent assay, respectively. The adrenal cortex ultrastructure was observed using electron microscopy. RESULTS: Compared with the quiet control group, after navigation and strenuous exercise, blood glucose was increased, and T level was decreased in the stress group (both P<0.01). The blood glucose, CORT, IL-1 and IL-2 levels were significantly reduced in the CM group (P<0.05 or P<0.01) as compared with the stress group. Electron microscopy revealed that the rats in the CM group had a smaller decrease in adrenal intracellular lipid droplets and higher levels of apoptosis than those in the stress group. CONCLUSIONS: Schisandra chinensis can reduce serum CORT and blood glucose levels in stressed rats. It appears to protect the cell structure of the adrenal cortex, and offset the negative effects of psychological stress and strenuous exercise related to immune dysfunction. Schisandra chinensis plays a regulatory role in immune function, and can decrease the influence of stress in rats.

Antihypertensive effect of Cu and Mg enriched modified poultry eggPsi on Zn-induced hypertension in Wistar rat.

PROJECT: Excessive bioavailability of Zn either due to genetic predisposition or its high concentration in diet has been linked to increase in the prevalence of hypertension (HT) implicating the resultant deficiencies of Cu and Mg as its cause in some populations. To combat their nutritional deficiencies, a modified poultry egg (ME(Psi)) was designed containing higher amounts of Cu, Mg and other antioxidants (vitamin E and linolenic acid) in their optimized concentrations. Prior to its human clinical trials, its efficacy was tested in Zn induced HT Wistar rat model in the present study. PROCEDURE: In one set, the rats were fed on equicaloric semi-synthetic basal diet containing 20 mg Zn/kg diet (control diet-I, control group-I), Zn-induced-hypertensive-diets-II and III (Zn-HT-diet-II and Zn-HT-diet-III) containing 40 and 80 mg Zn/kg diet (groups-II and III) for 180 days. In another set, the rats were initially fed Zn-HT-diet-II and Zn-HT-diet-III for 90 days and then shifted to ME(Psi) mixed Zn-HT-diet-II and III designated as groups-IIME and IIIME fed for another 90 days completing 180 days of feeding. RESULTS: The results revealed that increase in systolic pressure (SP) and heart rates (HR) were Zn concentration dependent and coincided well with higher serum Zn, Cu, Mg, aldosterone, cortisol, dyslipidemia and higher Zn, and low Cu and Mg concentrations in liver of groups-II and III rats. On feeding ME(Psi) mixed diets, a significant reduction in SP and HR were linked with decrease in serum Zn, Cu, Mg, aldosterone, cortisol and blood lipid profile along with fall in Zn and rise in Cu and Mg concentrations in liver of groups-IIME and IIIME approaching closer to control group-I. CONCLUSION: This study makes the basis for human clinical trials of ME(Psi) on HT patients who exhibit high Zn, Cu and Mg in their blood serum.

ATP depletion is associated with cytotoxicity of a novel lipid regulator in guinea pig adrenocortical cells.

A novel lipid regulator (PD132301-2) produces degeneration and necrosis of adrenal fasciculata in guinea pigs. Primary adrenocortical cell cultures from male Hartley guinea pigs were utilized to investigate potential mechanisms of this toxicity. Concentration-dependent loss of viability, measured by neutral red (NR) accumulation or MTT reduction, was observed within 6 hr at concentrations of 0.01 to 10 microM PD132301-2. At 10 microM, NR and MTT indices were 50% of those of control after 6 hr exposure. Maximal decreases in NR and MTT indices to 20% of control values occurred by 24 hr at > or = 1 microM PD132301-2. Adenine nucleotide analysis after PD132301-2 challenge indicated that ATP depletion preceded loss of viability. At 10 microM PD132301-2, ATP levels were 80% of those of control after 30 min and 25% of those of control after 6 hr. Supplementation of glucose-free buffer with 20 mM fructose protected adrenocortical cells from PD132301-2-induced toxicity. Fructose protection was blocked by inhibiting glycolysis with 1 mM sodium fluoride. Pretreatment of cultures with 100 microM metyrapone, an inhibitor of cytochrome P-450, did not block cytotoxicity induced by 10 microM PD132301-2, but did block cytotoxicity of 100 microM o,p'-DDD. In adrenocortical mitochondrial preparations, inhibition of respiration by PD132301-2 was site II-specific. Both state 3 and state 4 respiration were inhibited 50-75% at 1-30 microM PD132301-2. Thus, ATP depletion resulting from direct inhibition of mitochondrial respiration is a critical early event in adrenocortical cytotoxicity of PD132301-2.

[Pathological changes in adrenal cortex in rats after phosphorus burn (stereological and histochemical changes)].

The experiment dealt with stereological and histochemical study on the submicroscopic structure of adrenal cortex after phosphorus burn within 15 days. The main findings were as follows: (1). The increased dense lysosome-like bodies in the adrenal cortical cells after burn were not all lysosomes, and it was conjectured they were hormone carrier-protein which might come from the Golgi complex; (2). The ZR cells developed better and had more abundant organelles and higher enzymic activity than other zonal cells. These differences were more obvious after burn. We speculated that ZR was not a degenerated zone, but an important functional area of synthesis and secretion of steroid hormone; (3) Different cellular functional conditions in adrenal cortex were related to the secretory rhythm of the cells.

[An experimental study on pathological changes in adrenal cortex in rats after phosphorus burn. I. Ultrastructural changes].

We observed the ultrastructural (PCC) changes in the adrenal zona fasciculata (ZF) and zona reticularis (ZR) and plasma corticosterone levels after phosphorus burn in rats within 15 days. We found that the PCC in the burnt rats increased remarkably with 3 peaks, and all the organelles or the surface structures (filopodia and cytoplasmic processes) in ZF and ZR cells showed various changes, which we considered as variant forms of secretion and synthesis hyperfunction of the adrenal cortical cells. There were also degenerative changes in the membrane structure.

[Morphofunctional characteristics of adrenal reactivity in rats of different ages]. / Morfofunktsional'nye osobennosti reaktivnosti nadpochechnikov krys raznogo vozrasta.

Ultrastructural peculiarities of the cortical and medullary substance of the adrenals have been studied in mature (8-month-old) and old (26-month-old) intact white male rats and in rats of the same age groups in 3 h after electrical stimulation of the hypothalamic ventromedial nuclei. By means of certain biochemical methods contents of hormones (corticosterone, adrenaline and noradrenaline) have been estimated, as well as that of cholesterin and ascorbic acid in blood and adrenal tissues. After the hypothalamus is stimulated in the mature rats, certain peculiarities in the adrenals reactivity are revealed; they demonstrate positive ultrastructural and functional correlation of secretory cells in the cortex and medulla and are characterized with hypertrophy of the nuclei, increased amount of polyribosomes, hypertrophied Golgi complex and canaliculi of the endoplasmic reticulum and increased contents of corticosteroids and catecholamines in blood. In the old rats after stimulation of the hypothalamus, certain unequal ultrastructural and functional peculiarities are revealed. They demonstrate both disturbance of the hypothalamic regulation of the adrenal function at ageing and decreased adaptive possibilities of the adrenal secretory cells at the subcellular level.

The effect of 5-fluorouracil on rat adrenal function.

This study was undertaken to determine the effects of 5-fluorouracil on corticosteroidogenesis and adrenal size in the rat. The rats were injected intraperitoneally with 5-FU (12.5 mg kg-1 or 25 mg kg-1), normal saline or actinomycin D (0.02 mg kg-1), daily for 10 days. High-dose 5-FU induces adrenal hyperplasia, in association with mild impairment of corticosteroidogenesis (manifest by lower corticosterone and higher ACTH levels). The response to low-dose 5-FU and actinomycin D is of lesser adrenal hyperplasia, relative to high-dose 5-FU (P less than 0.05) and elevated corticosterone levels. There may be a dose-related effect on the suppression of corticosteroidogenesis in the rat by 5-FU.

Effect of castor oil and benzyl benzoate used as a vehicle for antiandrogens on the adrenal cortex.

The use of benzyl benzoate as a vehicle constituent in administering cyproterone acetate caused morphological changes detectable at the ultrastructural level in the adrenal cortex. Xastor oil and benzyl benzoate in a 4:1 ratio caused intracellular as well as intercellular changes. In the zona fasciculata there were alterations in mitochondrial shape, size, and matrix. Intercellular changes affected the morphology of macrophages in the zona fasciculata and zona reticularis. It is believed that the castor oil and benzyl benzoate vehicle caused stress-induced changes.

A preliminary investigation of the mechanism of anti-pain and counter-injury effects of the acupuncture anaesthesia.

In accordance with dialectical materialism and by dint of experimental acupuncture anaesthesia, the present investigation has: (1) Made an objective evaluation of the efficiency of acupuncture anaesthesia. (2) Brought forth some experimental evidence about the material basis of the anti-pain and counter-injury effect of acupuncture anaesthesia as well as the significance of its induction period. (3) Proposed the concept of humoral anaesthesia and its technique in order to improve the efficiency of animal laparotomies with acupuncture anaesthesia. Furthermore, it attempts to offer a theoretical explanation of the process of acupuncture anaesthesia under the combination of Chinese and Western medical theories and thereby gives some support to the "meridian-cerebral cortex-viscera inter-correlation hypothesis."

Ultrastructural study on the hypothalamic-hypophysial-adrenal axis in fetal rats.

The adrenal glands of decapitated and encephalectomized fetal rats were investigated electron microscopically and compared to those of normal intact fetal rats. Although the adrenal cortices did not show three zones (zona glomerulosa, fasciculata, and reticularis) on the 16.5th day of gestation when the decapitation or encephalectomy was carried out in utero, the zonation was recognized in fetuses operated on the 21.5th day of gestation. The same was true for normal control fetuses. However, cytoplasmic characteristics suggesting steroidogenesis in the cortical cells were reduced to various degrees in the encephalectomized or decapitated fetuses, especially in the latter ones. The change in cytoplasmic appearance was more conspicuous in the inner portion of the cortex. This result suggests that for the maintenance of normal adrenocortical function the hypothalamus may be indispensable even during the prenatal life of rats.

[Karyometric studies of the pancreas and adrenal glands of the albino-rat fed an unbalanced glucose diet or a glucose diet supplemented with thiamine]. / Karyometrische Untersuchungen an Pankreas und Nebenniere der Albinoratte bei einseitiger Glucose- und Glucose-Thiamin-Diät

Karyometric measurements in rats which for 30 days had received a glucose diet or a glucose diet supplemented with thiamine showed the following decrease in nuclear size in contrast to no treated controls. (see article) In both experimental groups there was a 30% loss of weight during the course of the experiment. The different decreases in nuclear volume in the examined organs cannot be explained only by a relative state of hunger. The very large decrease in activity in the fasciculated zone of the adrenal cortex is explained as an adaptation mechanism favouring glucose oxidation by insulin, and the relative increase in activity in the adrenal medulla as an adaptation mechanism to accomplish an elevated lipolysis.