Effects of glucocorticoids on differentiation of zona glomerulosa of fetal adrenal cortex of rats.

The tissue differentiation of the zona glomerulosa of the fetal adrenal cortex of rats was studied by giving experimental treatments to the fetus in vivo. A low-glucocorticoid-condition was given to the fetus by bilateral adrenalectomy of pregnant rats for removing exogenous glucocorticoids from the fetus, and by brain aspiration of the fetuses for removing the fetal pituitary gland (ACTH) and endogenous glucocorticoids. When the fetus was placed under a low-glucocorticoid-condition for the last couple of days of gestation, poor differentiation of the zona glomerulosa occurred specifically in the fetal adrenal cortex. The degree of the poor differentiation seemed to be proportional to the duration of the low-glucocorticoid-condition. Supplemental administration of glucocorticoids could prevent this poor differentiation of the zona glomerulosa. These results indicate that the tissue differentiation of the zona glomerulosa of the fetal adrenal cortex depends much on glucocorticoids.     

DIFFERENTIATION OF THE FETAL ADRENAL CORTEX OF RATS - ITS EXPERIMENTAL OBSERVATION In Vivo

The development and tissue differentiation of the adrenal cortex of rats were studied by giving experimental treatments to the fetus in vivo. A low-AGTH-condition was given to the fetus by administrating Dexamethasone through its mother, or directly into the subcutaneous tissue of the fetus, or by decapitation, brain aspiration or hypophysectomy. When the fetus was given the low-ACTH-condition for the last 5 days or more, the hypoplastic adrenal cortex developed specifically. It had nearly normal zona glomerulosa (ZG), and poorly differentiated zona fasciculo-reticularis (ZF-R) without differentiated ZF-R. The observing day was settled at 21 1/2 days old. The shorter the period of low-ACTH-condition was, the more thickened the differentiated zone (ZF-R) grew. On the contrary, the poorly differentiated layer became thinner in proportion to the period of low-ACTH-condition. The poorly differentiated cortical cell had ACTH-reactivity. It seems that the development and tissue differentiation of the ZF-R depend on fetal own ACTH, and poorly differentiated cortical cells appear below the ZG, and differentiate by ACTH and were gradually pushed inside. The zona glomerulosa develops and differentiates without dependence of ACTH. ACTA PATH. JAP. 27: 759-773, 1977.     

Differentiation of the fetal adrenal cortex of rats--its experimental observation in vivo.

The development and tissue differentiation of the adrenal cortex of rats were studied by giving experimental treatments to the fetus in vivo. A low-ACTH-condition was given to the fetus by administrating Dexamethasone through its mother, or directly into the subcutaneous tissue of the fetus, or by decapitation, brain aspiration or hypophysectomy. When the fetus was given the low-ACTH-condition for the last 5 days or more, the hypoplastic adrenal cortex developed specifically. It had nearly normal zona glomerulosa (ZG), and poorly differentiated zona fasciculo-reticularis (ZF-R) without differentiated ZF-R. The observing day was settled at 21 1/2 days old. The shorter the period of low-ACTH-condition was, the more thickened the differentiated zone (ZF-R) grew. On the contrary, the poorly differentiated layer became thinner in proportion to the period of low-ACTH-condition. The poorly differentiated cortical cell had ACTH-reactivity. It seems that the development and tissue differentiation of the ZF-R depend on fetal own ACTH, and poorly differentiated cortical cells appear below the ZG, and differentiate by ACTH and were gradually pushed inside. The zona glomerulosa develops and differentiates without dependence of ACTH.     

EFFECTS OF EXOGENOUS ACTH ON THE RAT FETAL ADRENAL CORTEX: A HISTOCHEMICAL AND ELECTRON-MICROSCOPICAL OBSERVATION

ACTH was administered subcutaneously to rat fetus directly at the late stage of fetal development and acute reaction on the fetal adrenal cortex was observed histochemically and electron microscopically. By administration of ACTH the adrenal cortex became remarkably hyperemic and there were swollen cells in all layers, particularly in the middle and inner layers (corresponding to the zona fasciculata and reticularis in adult rat). Marked reduction of lipid, enlarged mitochondria with increased vesicular cristae and increased smooth-surfaced endoplasmic reticulum (SER) were characteristic. The alterations of mitochondria preceded the change of SER, and thereafter mitochondria showed rapid degeneration. The outer layer (corresponding to the zona glomerulosa in adult rat) also showed similar changes by ACTH to those of the other two layers. These results indicated that the fetal adrenal cortex of rats was exogenous ACTH-reactive and its reaction which was different from that of adult cortical cells, seemed to be speciflcally related to the development and differentiation of the cells. ACTA PATH. JAP. 27 : 477–484, 1977.     

Effects of exogenous ACTH on the rat fetal adrenal cortex: a histochemical and electron-microscopical observation.

ACTH was administered subcutaneously to rat fetus directly at the late stage of fetal development and acute reaction on the fetal adrenal cortex was observed histochemically and electron microscopically. By administration of ACTH the adrenal cortex became remarkably hyperemic and there were swollen cells in all layers, particularly in the middle and inner layers (corresponding to the zona fasciculata and reticularis in adult rat). Marked reduction of lipid, enlarged mitochondria with increased vesicular cristae and increased smooth-surfaced endoplasmic reticulum (SER) were characteristic. The alterations of mitochondria preceded the change of SER, and thereafter mitochondria showed rapid degeneration. The outer layer (corresponding to the zona glomerulosa in adult rat) also showed similar changes by ACTH to those of the other two layers. These results indicated that the fetal adrenal cortex of rats was exogenous ACTH-reactive and its reaction which was different from that of adult cortical cells, seemed to be specifically related to the development and differentiation of the cells.     

Quantitative ultrastructural study of the rat adrenal cortex in renal encapsulation-induced hypertension.

Hypertension was induced in young rats by latex encapsulation of both kidneys. By the fourth week, 85% of the renal-encapsulated (RE) rats became hypertensive. Varying degrees of cardiovascular involvement were evident in the moderately to severely hypertensive rats. The level of systolic blood pressure was directly correlated with the width and the volume of zona glomerulosa of the adrenal cortex. Electron microscopy combined with morphometric-stereologic techniques was employed to quantitate change in the adrenal cortex. The cells of both zona glomerulosa and zona fasciculata of RE rats showed significant increases in the volume of the cell, nucleus, smooth endoplasmic reticulum, and lipid droplets; only in the zona glomerulosa cells was the increase in surface area of the smooth endoplasmic reticulum statistically significant. It is suggested that these structural changes associated with renal-encapsulation hypertension are related at least in part to stress of the hypertensive cardiovascular disease.     

The effect of zinc deficiency on the ultrastructure of rat adrenal cortex

The adrenal cortex of male Sprague-Dawley weanling rats maintained on a zinc-deficient diet was studied by electron microscopy. There was a gradual increase in lipid droplets in the zona fasciculata which was quite marked at 7 weeks, but increased lipid was not observed in the zona glomerulosa or reticularis of zinc-deficient rats. The adrenal cortex of the control animals did not show altered lipid content. A possible explanation for the effect of zinc deficiency on the adrenal cortex is offered.     

人胎儿肾上腺的组织发生

用光镜、透射电镜观察了４例胚、９０例胎，４例新生儿肾上腺。结果表明，７周胚已可分辨胎儿皮质和永久皮质，１５周时永久皮质开始分化，出生时初级球状带和束状带已形成，网状带未出现；７周时神经嵴细胞开始迁入肾上腺，１３周时髓质形成，嗜铬细胞出现，１６周时交感神经节细胞出现，出生时仍有少量神经嵴细胞向肾上腺内迁移。     

The adrenal cortex in spontaneously hypertensive rats. A quantitative ultrastructural study.

The adrenal cortex of spontaneously hypertensive rats (SHR) has been examined by quantitative morphologic techniques for electron microscopy. The volume and surface area of smooth endoplasmic reticulum and the volume of Golgi apparatuses in zona glomerulosa cells of SHR was significantly greater than those of Wistar-Kyoto strain (W/KY) normotensive controls; the volume of lipid droplets and nucleus was significantly less in SHR than in W/KY animals. A stimulation of the zona glomerulosa in SHR may well be attributable to the elevation in systolic blood pressure. A distinct lipid-free subglomerulosa was observed in the adrenal gland of W/KY rats; the cell volume was similar to that of the zona glomerulosa although the cells showed a significantly greater volume of mitochondria and surface area of mitochondrial membranes and greater volume of smooth endoplasmic reticulum and lysosomes. In the zona fasciculata, cell volume, volumes and surface area of mitochondria and smooth endoplasmic reticulum, and volume of lipid droplets were significantly lower in SHR than in W/KY rats. The volume of the Golgi apparatus was greater in SHR than in W/KY rats. Glycogen particles were observed in focal areas of some zona fasciculata cells. The adrenal cortex of another strain of normotensive Wistar rat (W/CFN) was compared with that of the W/KY and SHR. Although the relative adrenal weights of SHR and W/KY animals were identical, the weight of that in W/CFN was significantly smaller. The volume of the zona glomerulosa of SHR was significantly greater than that of W/KY although the volume of the zona glomerulosa in W/CFN was significantly greater than the other two groups. The volume of nucleus and lipid droplets of zona glomerulosa in W/KY was significantly greater than that in the S/CFN; the volume of the cell, mitochondria, smooth endoplasmic reticulum, lipid droplets, and lysosomes, and the surface area of smooth endoplasmic reticulum and mitochondrial membranes of W/KY animals was significantly greater than those of W/CFN animals. It is concluded that the W/CFN rat is not an appropriate control for spontaneously hypertensive rats.     

雌性大鼠肾上腺皮质形态及功能的增龄变化

30只Wistar雌性大鼠分为青年组(3～4月龄)、中年组(12～14月龄)及老年组(24～26月龄)。用光镜、电镜及放射免疫技术对其肾上腺皮质进行了形态及功能增龄变化的研究。见老年大鼠球状带变薄,血浆醛固酮浓度下降;束状带结构紊乱,出现出血灶,部分线粒体嵴退化、消失,滑面内质网扩张,胞浆呈现空泡,脂滴减少;网状带溶酶体及脂褐素增多,细胞间胶原纤维增多,血浆脱氢表雄酮(DHEA)浓度下降。提示老年大鼠肾上腺皮质发生了退行性变化。     

ZONATION OF THE ADRENAL CORTEX II. EFFECT OF BSA ON COUPLING EFFICIENCY OF MITOCHONDRIA ISOLATED FROM THE ZONA GLOMERULOSA OF THE BOVINE ADRENAL CORTEX

Effect of bovine serum albumin on coupling efficiency of mitochondria Isolated from the zona glomerulosa of the bovine adrenal cortex in various media was examined polarographically and electron microscopically. Albumin restored the coupling efficiency of mitochondria isolated from the zona glomerulosa regardless of isolation media when succinate or malate was oxidizable substrate. Respiratory controls greater than 5 were obtained. Albumin, however, had no effect when glutamate, β-hydroxybutylate and pyruvate were the oxidizable substrates. The conditions have been found under which mitochondria of the zona glomerulosa stay In the orthodox configuration and yet coupled.     

ZONATION OF THE ADRENAL CORTEX

Isolation procedures for mitochondria from the zona glomerulosa of the bovine adrenal cortex are described in comparison to those isolated from the zona fasciculo-reticularis. The cristal membranes of mitochondria in the zona glomerulosa in situ are tubular or tubulo-vesicular, whereas those of mitochondria in the zona fasciculo-reticularis in situ are vesicular. When mitochondria are isolated from the former zone, they Invariably showed a condensed configuration regardless of isolation media, whereas those isolated from the latter zone in a ST medium showed an orthodox configuration. When Ca²⁺ was added to mitochondria isolated from either zone in an STE medium in the condensed configuration, transition from the condensed to the orthodox configuration took place; the cristel membrane of mitochondria from the zona glomerulosa became tubular or tubulo-vesicular and those of mitochondria from the zona fasciculo-reticularis became vesicular. Purity of mitochondria thus obtained from the zona glomerulosa was examined by electron microscope and marker enzymes. Coupling efficiency of mitochondria was found to be remarkably affected by temperature during the isolation procedures and a choice of substrates.     

Effect of enalapril injected in the early period of postnatal ontogeny on structure of adrenal glands in mature hypertensive NISAG rats

Blood pressure in 6-month hypertensive NISAG rats daily treated with enalapril in the early postnatal period was lower than in control rats. Enalapril produced significant morphological alterations only in the zona glomerulosa of the adrenal cortex. The volumes of this area and the corresponding endocrine cells were lower than in the control. Enalapril produced a delayed modifying effect on the structure of the adrenal zona glomerulosa by moderating hyperplasic alterations, which are characteristic of intact mature NISAG rats. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 141, No. 2, pp. 133–136, February, 2006     

Degeneration of the rat and canine adrenal cortex caused by alpha- (1,4-dioxido-3-methylquinoxalin-2-yl) -N-methylnitrone (DMNM)

The antibacterial drug alpha- (1,4-dioxido-3-methylquinoxalin-2-yl)-N-methylnitrone (DMNM) given at a dose of 22.5 mg/kg/bid to 4 dogs for 14 days caused diminished adrenal cortical reserves as determined by decreased plasma corticol (3 dogs) and lower aldosterone levels (4 dogs) following the intravenous infusion of ACTH. A dose of 100 mg/kg/day of DMNM administered to rats for 31 or 35 days resulted in significant decreases in blood glucose. Histologically, the adrenal glands of both species treated with DMNM for a maximum period of 21 days (dogs) and 35 days (rats) had widespread granular and vacuolar degeneration of the cortex. The degeneration, as demonstrated in treated rats, began in the zona reticularis and inner regions of the zona fasciculata and eventually involved the entire cortex including the zona glomerulosa. As a result of treatment, significant ultrastructural alterations within cells of the rat and canine adrenal cortex consisted of degeneration of the mitochondria and an increase in the numbers and lipolysis of lipid droplets. The ultrastructure of the zona reticularis and fasciculata was most severely affected.     

大鼠肾上腺的NADPH,NPY,CGRP,SP,c—fos细胞化学特性

目的 探讨肾上腺内分泌组织和神经组织的双重组织学特性。方法 组织化学和免疫组织化学技术,在光学显微下观察ＮＡＤＰＨ、ＮＰＹ、ＣＧＲＰ、ＳＰ、ｃ－ｆｏｓ在大鼠肾上腺的分布。结果 肾上腺皮质分布有ＮＰＹ阳性神经细胞和神经纤维、ＣＧＲＰ阳性神经纤维;肾上腺髓质分布有ＮＡＤＰＨ－ｄ阳性神经细胞和神经纤维、ＣＧＲＰ阳性神经纤维、ＳＰ阳性神经纤维、ｃ－ｆｏｓ阳性神经细胞和神经纤维。肾上腺皮质球状带、网状带、束状带细胞均ＮＡＤＰＨ－ｄ阳性,髓质部分嗜铬细胞ＮＡＤＰＨ－ｄ阳性,部分嗜铬细胞ＮＰＹ阳性,部分嗜铬细胞ＣＧＲＰ阳性,部分嗜铬细胞ＳＰ阳性。结论 大鼠肾上腺接受广泛的非经典递质的神经支配,特别是肽能神经支配的肾上腺实质细胞及髓质嗜铬细胞,能分泌多种神经肽物质。提示肾上腺的内分泌活动不仅受到复杂的神经调节而且也受到自身的活     

卵巢切除对大鼠肾上腺雌激素受体亚型表达的影响

目的通过对去卵巢大鼠雌激素受体(ER)亚型在肾上腺表达的观察,研究去卵巢对大鼠肾上腺功能影响的机制。方法选择成年Wistar大鼠20只,10只为假手术组,10只为模型组(去卵巢组),6周后处死大鼠,分离摘取肾上腺,称重后常规石蜡包埋切片,分别进行ERα、ERβ抗体的免疫组织化学染色,并取动物血清测量雌二醇(E2)和促卵泡生成素(FSH)的含量。结果1.ERα与ERβ在大鼠肾上腺均有表达,主要分布在肾上腺皮质部,以球状带和束状带为主,网状带有少量分布,ERβ的表达强于ERα。2.ERβ在大鼠模型组的表达强于假手术组,有统计学意义,ERα在模型组的表达略强于假手术组,但无统计学意义。3.卵巢切除后,大鼠血清FSH升高,E2下降,与假手术组相比,有显著差异。结论卵巢切除可影响雌激素受体在大鼠肾上腺的表达,尤其是对ERβ表达的影响较为显著。卵巢切除能够减少大鼠血清雌激素的分泌,使垂体反馈性的增加FSH的分泌。     

Spironolactone bodies in an adrenal adenoma.

Spironolactone bodies were observed in an adrenal cortical adenoma that was removed from a patient with primary hyperaldosteronism (Conn syndrome) treated preoperatively with spironolactone. The electron microscopical evaluation of this adrenal cortical adenoma shows origin of spironolactone bodies from whorls of endoplasmic reticulum in cells with the cytoplasmic features of those from the zona glomerulosa of the adrenal gland. There was no evidence that the bodies were derived from mitochondria, which confirms recent ultrastructural findings in patients treated with spironolactone. These bodies have been described in the adrenal cortex only in patients who have received spironolactone, and the pharmacologic specificity of the bodies strongly suggests a direct mode of action by spironolactone on aldosterone production by cells of the adrenal zona glomerulosa.     

Fine structure and morphogenesis of spironolactone bodies in the zona glomerulosa of the human adrenal cortex

Numerous spironolactone bodies have been detected in the zona glomerulosa cells of the adrenal cortex of a 36-year-old spironolactone-treated woman whose non-tumorous right adrenal gland was removed surgically because of primary hyperaldosteronism. Electron microscopy revealed spherical laminated whorls which consisted of a central core composed of an amorphous electron-dense material surrounded by numerous smooth-walled concentric membranes. Continuous with and deriving from the endoplasmic reticulum, they were present in viable cells and were not associated with ultrastructural features indicating cellular injury. Cytoplasmic inclusions similar to spironolactone bodies can be detected in other organs after the administration of various compounds. Thus, they can be regarded as neither specific to spironolactone treatment nor exclusively inducible in the zona glomerulosa of the adrenal cortex.     

HISTOCHEMICAL AND ULTRASTRUCTURAL STUDIES OF THE ADRENAL CORTEX IN SPONTANEOUSLY HYPERTENSIVE RATS WITH HIGH SALT SOLUTION

The response of the adrenal cortex In weanling Spontaneously Hypertensive Rats (SHR, OKAMOTO and AOKI) and Wistar-Kyoto Rats (WKR) when given 1% NaCl In drinking water was studied histochemically and electron microscopically. The development of hypertension was accelerated in SHR given 1% NaCl in drinking water. The thickness of the zona glomerulosa In WKR receiving 1% NaCl in drinking water remarkably diminished following the course of experiment and lipid droplets In the zona glomerulosa decreased gradually. The zona glomerulosa cells revealed shrinkage of the cells and a decreased number of mitochondrial crlstae were observed at three weeks of experiment. The remaining tubular crlstae of mitochondria possessed a milled outline. Golgi apparatus became small and fragmental. Membrane -bounded dense bodies were prominent in the peripheral portion of the cell and around Golgl apparatus. In SHR given 1% NaCl in drinking water, the width of the zona glomerulosa less diminished. A marked decrease in number and size of lipid droplets was seen. However, there was no distinct alteration of cytoplasmic organelles. These morphological changes were discussed from the standpoint of functional state In the zona glomerulosa with relation to the development of hypertension in SHR.     

应用组织芯片技术研究A103和inhibin α在肾上腺皮质肿瘤中的诊断价值

目的 研究肾上腺皮质肿瘤的免疫组织化学和临床病理特点及A103与inhibin α在其中的诊断价值并探讨组织芯片技术的可行性。方法 制备肾上腺皮质腺瘤(ACA)、肾上腺皮质癌(ACC)及嗜铬细胞瘤组织芯片各1个。肾上腺皮脂腺瘤芯片(79例),其中正常肾上腺皮质3例,胎儿肾上腺皮质2例,肾上腺皮质结节状增生2例,ACA72例;肾上腺皮质癌芯片(56例),其中ACC39例,肾上腺转移肿瘤17例(恶性黑色素瘤4例,转移癌13例);嗜铬细胞瘤芯片(44例)中含肾上腺髓质3例,嗜铬细胞瘤41例;20例正常成人肾上腺的常规石蜡组织作对照。用免疫组织化学EnVision法检测A103、inhibin α、calretinin、Ki-67等的表达情况。结果 A103阳性表达情况分别为正常肾上腺皮质100％(23／23),胎儿肾上腺皮质2／2,皮质增生2／2,ACA90．9％(60／66),ACC94．6％(3,5／37),肾上腺髓质及嗜铬细胞瘤阴性,转移肿瘤中除恶性黑色素瘤3／3阳性外其余均为阴性;inhibin α在正常肾上腺皮质、胎儿肾上腺皮质及皮质增生中100％表达,阳性部位主要在网状带与束状带内层,ACA阳性率75．8％(50／66),ACC75．7％(28／37),肾上腺髓质、嗜铬细胞瘤及转移肿瘤均为阴性。结论 组织芯片技术为快速原位检测提供了强有力的手段。应用组织芯片技术大规模高效检测组织样本是可行的。A103及inhibin α的联合应用对于明确肾上腺皮质肿瘤的诊断与鉴别诊断有较高价值。