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.

Histologic evaluation of parovarian nodules in the cat.

OBJECTIVES: A notable, although relatively uncommon, finding during feline ovariohysterectomy is the presence of parovarian nodules, located proximal to the ovary, near or within the ovarian vascular bundle. They are usually 2-3 mm in diameter, white-to-tan in color and glandular in appearance. The objective of this study was to either decisively reinforce the existing findings reported in the literature, which suggest that these parovarian nodules are incidental adrenocortical nodules that are clinically and surgically insignificant, or capture any samples that were not ectopic adrenal tissue in order to characterize them histologically. METHODS: Ninety-one formalin-preserved tissue sections containing parovarian nodules were collected during routine feline elective ovariohysterectomy and evaluated histologically. RESULTS: Definitive histologic information was obtained from 73/91 (80.2%) submitted samples. Fifty-two of 73 (71.2%) samples were determined to contain accessory adrenal gland cortex. Twenty of 73 (27.4%) samples were determined to contain residual mesonephric structures. While accessory adrenocortical nodules were found bilaterally in cats of all ages, mesonephric structures were predominantly right-sided, and only found in one cat over the age of 1 year. Ectopic or accessory ovarian tissue was not found in any of the samples. CONCLUSIONS AND RELEVANCE: This study adds to the existing body of data which suggest these nodules are incidental structures that do not need to be removed during surgical sterilization. However, further in vivo studies with larger sample sizes and years of follow-up would be required to more definitively prove this theory.

Hipertensión arterial mal controlada secundaria a quiste vascular suprarenal / Vascular adrenal cyst causing difficult to control high blood pressure

La hipertensión arterial supone un importante problema de salud pública en los países desarrollados. Las masas suprarrenales pueden pasar desapercibidas, ya que no son lesiones frecuentes y no producen síntomas o no se les atribuyen directamente. Estas circunstancias hacen que sea fundamental la actuación médica multidisciplinar. Comunicamos el caso de una mujer de 72 años, hipertensa mal controlada de años de evolución (3 fármacos antihipertensivos, sin alcanzar la tensión arterial en rango de normalidad), remitida por hallazgo incidental de lesión retroperitoneal derecha. Se diagnostica de quiste de origen suprarrenal posiblemente responsable del cuadro hipertensivo. Realizamos revisión de la literatura analizando diferentes actitudes diagnósticas y terapéuticas. Tras adrenalectomía por abordaje laparoscópico, conseguimos estabilizar a la paciente en cifras de tensión arterial dentro de la normalidad. La integración coordinada de servicios médicos y quirúrgicos es clave para el manejo de situaciones clínicas poco frecuentes. La cirugía laparoscópica constituye el tratamiento de elección en la enfermedad retroperitoneal (AU)

Hypertension is a prevalent disease in developed countries. Adrenal masses, and especially adrenal cysts, are a rare and usually asymptomatic finding, which can go unnoticed or be detected as incidental findings in imaging tests. These circumstances make the multidisciplinary approach mandatory. The case is presented on a 72 year-old woman with uncontrolled high blood pressure referred to the Urology Department due to the incidental finding of a right retroperitoneal mass. A functional and imaging study was performed, establishing a diagnosis of adrenal cyst causing hypertensive symptoms. A literature search was performed in order to assess diagnostic and therapeutic approaches. With the diagnosis of adrenal cyst causing uncontrolled high blood pressure, a right laparoscopic adrenalectomy was performed. After surgery the patient has maintained blood pressure within the normal range. A multidisciplinary approach is necessary for the management of rare diseases. The surgical approach, if possible, should be laparoscopic (AU)

Regulation of zonation and homeostasis in the adrenal cortex.

The adult adrenal cortex is organized into concentric zones, each specialized to produce distinct steroid hormones. Cellular composition of the cortex is highly dynamic and subject to diverse signaling controls. Cortical homeostasis and regeneration rely on centripetal migration of steroidogenic cells from the outer to the inner cortex, which is accompanied by direct conversion of zona glomerulosa (zG) into zona fasciculata (zF) cells. Given the important impact of tissue structure and growth on steroidogenic function, it is essential to understand the mechanisms governing adrenal zonation and homeostasis. Towards this end, we review the distinctions between each zone by highlighting their morphological and ultra-structural features, discuss key signaling pathways influencing zonal identity, and evaluate current evidence for long-term self-renewing stem cells in the adult cortex. Finally, we review data supporting zG-to-zF transdifferentiation/direct conversion as a major mechanism of adult cortical renewal.

[Heterozygosity for Mutations Affecting Coat Pigmentation in the American Mink (Neovison vison) Enhances Structural Stability of Adrenal Cortex under Stress Conditions].

The results of the study of the effects of heterozygosity for mutations affecting coat pigmentation on the response to the environmental stress caused by extreme feeding conditions are provided. The animals with the following genotypes were taken into the study: homozygotes standard (+/+), hedlund white (h/h), and aleutian (a/a) and heterozygotes hedlund white (h/+) and aleutian (a/+). The animals homozygous for the aleutian mutation (a/a) showed a statistically lower growth rate than the animals of other genotypes both in the ontrol and in the experiment (p < 0.05). Under the control conditions, the animals homozygous forboth the wild type standard allele (+/+) and the mutant hedlund white (h/h) and aleutian (a/a) alleles showed the evident tendency for the zona fasciculata and zona reticularis of the adrenal cortex broadening compared to the experimental conditions. At the same time, in the animals heterozygous for the hedlund white (h/+) and the aleutian (a/+) mutations, a clear tendency for increasing size of the zona fasciculata and zona reticularis under the experimental conditions was observed. In the heterozygous animals, although we observed single destructive changes in the adrenal cortex under stress conditions, they were much less profound than in the homozygous ones. This may be related to the broader range of morphological adaptation in the heterozygotes, which gives them the possibility of more significant enlargement of the secreting zone to provide for its adequate functioning.

Histocytological specificities of adrenal cortex in the New World Monkeys, Aotus lemurinus and Saimiri boliviensis.

The New World monkey Aotus spp. (night monkeys) are expected for use of valuable experimental animal with the close species of Saimiri spp. (squirrel monkeys). Saimiri is known to show spontaneous hypercortisolemia, although few reports in Aotus. We compared basic states of blood steroid hormones and histological structure of the adrenal glands in two monkeys. Serum cortisol and ACTH levels were statistically lower in Aotus than Saimiri. Conversely, Aotus adrenocortical area showed significant enlargement, especially at the zona fasciculata. Electron microscopic observation at Aotus fasciculata cells revealed notable accumulation of large lipid droplets and irregular shapes of the mitochondrial cristae. These results suggest potential differences in cellular activities for steroidogenesis between Aotus and Saimiri and experimental usefulness in adrenocortical physiology and pathological models.

Chronic welfare restrictions and adrenal gland morphology in broiler chickens.

Gait problems constitute an important and chronic welfare restriction for broiler chickens. The objective of the present study was to determine if adrenal gland morphology indicates chronic welfare restrictions in broiler chickens, using gait problems as the stressor. Sixty-six birds raised on a commercial unit were selected at 40 d of age and separated into groups according to gait score. One group was apparently healthy birds (AH) with gait scores of 0 to 2, and the other group had birds with gait problems (GP) that showed gait scores of 4 to 5. Birds were slaughtered and weighed, and their adrenal glands were measured and weighed; proportions of medullary and adrenocortical tissues, and lymphatic tissue and blood vessels were studied. GP birds had lower BW when compared to AH birds, and when adrenal gland weight values were adjusted to BW, a greater relative adrenal weight was observed for the GP group. Adrenals from GP birds also presented a higher proportion of blood vessels when compared to AH birds. These results might indicate increased adrenal activity and evidence of the inflammatory process as a consequence of chronic stress. Results showed that gait problems caused significant adrenal gland changes, suggesting a possible role for the study of adrenal gland morphology as an indicator of chronic welfare problems in broiler chickens.

Chromaffin cells of the adrenal gland in the beagle dog.

The distribution of adrenal chromaffin cells in the control beagle dog was investigated. The presence of chromaffin cells in the adrenal medulla, three zones of the adrenal cortex and capsule was identified by staining with H&E, chromium salts and TH (tyrosine hydroxylase) antibody. With H&E stain, there are morphological differences among the chromaffin cells in the medulla, cortex and capsule. In addition, the number of the capsular chromaffin cells was statistically significantly decreased in the 8-9, 11-12 and 15-16 month age groups compared with the 5-6 month age group. Both medullary and extra-medullary chromaffin cells contained catecholamines, demonstrated via special staining for chromium salts. TH is the first enzyme in catecholamine biosynthesis; it is a useful maker for all cells involved with catecholamine biosynthesis including chromaffin cells. TH antibody confirmed that the extra-medullary cells were chromaffin cells. Terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay for detecting the apoptotic signalling identified the apoptosis of the chromaffin cells in the capsule.

Adrenarche: a cell biological perspective.

Adrenarche is a cell biological and endocrinological puzzle. The differentiation of the zona reticularis in childhood in humans requires special techniques for study because it is confined to humans and possibly a small number of other primates. Despite the rapid progress in the definition of adrenocortical stem/progenitor cells in the mouse, the factors that cause the differentiation of adrenocortical cells into zonal cell types have not been identified. There are, however, many candidates in the Wnt, Hedgehog, and other families of signaling molecules. A suitable system for identifying authentic stem cells, capable of differentiation into all zones, has yet to be developed. It is proposed here that the in vitro differentiation of pluripotent cells, combined with appropriate in vitro and in vivo methods for validating authentic adrenocortical stem cells, is a promising approach to solving these questions.

Prenatal development of the adrenal gland in the one-humped camel (Camelus dromedarius).

UNLABELLED: With 14 figures and 3 tables SUMMARY: Each adrenal gland consisted of cortex and medulla that developed from different embryological origins and presented different cellular organization. One hundred male or female camel embryos or fetuses with crown vertebral rump lengths (CVRL) that ranged from 0.8 to 117 cm were examined. The adrenal cortex, which is derived from intermediate mesoderm, was first observed in the 0.8-cm CVRL camel embryo. The adrenal cortex initially was combined with the gonad as a thickened region of proliferating cells derived from splanchnic intermediate mesoderm. Adrenocortical tissue was first separated from the gonadal tissue in the 2-cm CVRL camel fetus and was observed as a separate dorso-medial mass of cells. At 2.5-cm CVRL, the adrenocortical tissue was surrounded by a capsule of undifferentiated mesenchymal cells, except at its proximal pole, where an invagination was located through which chromaffinoblast cells entered the cortex. The chromaffinoblast cells migrated from the neural crest to form the medulla of the developing adrenal gland. In the 3.5-cm CVRL camel fetus, the adrenocortical cells differentiated into two layers: the inner fetal cortex and the outer definitive cortex. As development proceeded, the fetal cortex degenerated and the definitive cortex formed the zona glomerulosa and zona fasciculata. The zona reticularis did not form until the end of gestation. During prenatal life, the adrenal medulla was much thicker than the cortex.

[Evaluation of androstenedione adrenal content and effects of castration on the domestic rabbit (Oryctolagus cuniculus)]. / Evaluation du contenu surrénalien en androstènedione et effets de la castration chez le lapin domestique (Oryctolagus cuniculus).

DHEA, DHEA sulphate and androstenedione are C19 steroïds secreted by the adrenal cortex. These hormones with a weak androgen activity are precursors of estrogens and androgens. In human and other primates these hormones are produced in important quantities, even though, in domestic and laboratory animals, a few secretion is measured. In this survey, the androstenedione is quantified both in plasma and adrenal gland of young, prepubertal and adult rabbits and the castration effects on adrenal cortex histology are noted too. The absolute weight (AW) of the left adrenal gland is slightly higher than the right (p>0.05) for all animals and the gland absolute weight (AW) for the adult rabbit is superior to the young and prepubertal rabitts (p<0.05). The castration effect in adult increases the adrenal weight (p<0.001). A zonation of adrenal cortex for young rabbits is observed. The zona fasciculata is important for young and prepubertal rabbits whereas, the zona reticularis is thicker for the adults. Thickness of glomerulosa, fasciculata and reticularis zonas increased with 6.55% (p>0.05), 15.9% (p<0.01) and 79.21% (p<0.001) for the castred adult rabbits and histological modifications were observed in the zona reticularis. The plasma androstenedione is negligible for the young (0.060+/-0.01 ng/mL), weak for the prepubertal (0.152+/-0.03 ng/mL) and reaches (0.263+/-0.03 ng/mL) for the adult. The androstenedione relative content (ng/100 mg of adrenal weight) is 2.90+/-0.30; 4.54+/-0.82 and 1.34+/-0.36 for the young, prepubertal and adult rabbits. In this work, an increase of the androstenedione adrenal content is observed for the prepubertal rabbits, which could intervene in the process of puberty.

Central effects of ghrelin on the adrenal cortex: a morphological and hormonal study.

Ghrelin, a growth hormone secretagogue that exerts an important role in appetite and weight regulation, participates in the activation of the hypothalamo-pituitary-adrenal (HPA) axis. Male Wistar rats (5/group) received daily for 5 days, via an ICV (intracerebroventricular) cannula, 5 microl phosphate buffered saline with or without 1 microg of rat ghrelin. Two hours after the last injection, blood and adrenal glands were collected from decapitated rats for blood hormone analyses and histologic and morphometric processing. Ghrelin treatment resulted in increased (p<0.05) body weight (13%), absolute whole adrenal gland weight (18%) and whole adrenal gland volume (20%). The absolute volumes of the entire adrenal cortex, ZG, ZF, and ZR also increased (p<0.05) after ghrelin by 20%, 21%, 21% and 11%, respectively. Ghrelin-treated rats had elevated (p<0.05) blood concentrations of ACTH, aldosterone and corticosterone (68%, 32% and 67%, respectively). The data clearly provide both morphological and hormonal status that ghrelin acts centrally to exert a global stimulatory effect on the adrenal cortex. Clarifying of the ghrelin precise role in the multiple networks affecting the stress hormone release, besides its well known energy and metabolic unbalance effects, remains a very important research goal.

SUMO and ubiquitin modifications during steroid hormone synthesis and function.

Steroid hormones control many aspects of animal physiology and behaviour. They are highly regulated, among other mechanisms, by post-translational modifications of the transcription factors involved in their synthesis and response. In the present review, we will focus on the influence of SUMO (small ubiquitin-related modifier) and ubiquitin modifications on the function of transcription factors involved in adrenal cortex formation, steroidogenesis and the hormonal response.

Molecular imaging of adrenal gland by desorption electrospray ionization mass spectrometry.

Subtle differences in the spatial distributions of closely related compounds including norepinephrine and epinephrine as well multiple lipids are easily distinguished in adult porcine (17 x 8 mm) and rabbit (7 x 4 mm) adrenal glands in a DESI-MS imaging experiment at atmospheric pressure with a spatial resolution of approximately 200 microm. Sensitive and specific detection in the course of DESI imaging discloses details of catecholamine distribution in porcine adrenal medulla and cortex; the average mass of epinephrine interrogated in each pixel is estimated to be about 150 pg. The distribution of ascorbic acid was revealed in the negative ion mode. In addition, the distribution of cholesterol, which cannot be observed using conventional DESI, was obtained using in situ reaction with betaine aldehyde added to the DESI spray while imaging the porcine adrenal gland tissue. Four characteristic types of distributions were observed, with major amounts of the components in the medulla, the cortex, the reticular zone or in the fourth case, being homogeneously distributed. The results agree with and extend information available from histological studies.

Quantitative analysis of patch patterns in mosaic tissues with ClonalTools software.

Quantitative analysis of mosaic tissues is a powerful method for following developmental lineages; however, analytical techniques are often subjective and repetitious. Here a flexible, semi-automated image analysis method for mosaic patterns is described. ClonalTools is a free customizable tool-set designed for the open-source image analysis package ImageJ. Circular, polygonal or linear one-dimensional mosaic arrays can be interrogated to provide measurements of the total number and width of positive and negative patches in a region of interest. These results are adjusted for the effects of random clumping using a previously described method to correct for differences in the contribution of the positive and negative cell type. The applicability of ClonalTools to different systems is discussed with reference to the analysis of mosaic patterns in the mouse corneal epithelium and adrenal cortex and in the outgrowth of neurites from explant cultures of mouse retina as example systems. To validate ClonalTools quantitatively, a recently published manual clonal analysis of the corneal epithelium of X-inactivation beta-Gal-mosaic mice was re-analysed. The semi-automated results did not differ significantly from the published data. Rapid quantification of such patterns to produce biologically relevant results represents a welcome improvement in terms of ease and speed of use over previous methods.

Development of the human adrenal zona reticularis: morphometric and immunohistochemical studies from birth to adolescence.

Age-related morphologic development of human adrenal zona reticularis (ZR) has not been well examined. Therefore, in this study, 44 human young adrenal autopsy specimens retrieved from large archival files (n=252) were examined for immunohistochemical and morphometric analyses. Results demonstrated that ZR became discernible around 4 years of age, and both thickness and ratio per total cortex of ZR increased in an age-dependent fashion thereafter, although there was no significant increment in total thickness of developing adrenal cortex. We further evaluated immunoreactivity of both KI67 and BCL2 in order to clarify the equilibrium between cell proliferation and apoptosis in the homeostasis of developing human adrenals. Results demonstrated that proliferative adrenocortical cells were predominantly detected in the zona glomerulosa and partly in outer zona fasciculata (ZF) before 4 years of age and in ZR after 4 years of age, but the number of these cells markedly decreased around 20 years of age. The number of BCL2-positive cells increased in ZR and decreased in ZF during development. Adrenal androgen synthesizing type 5 17beta-hydroxysteroid dehydrogenase (HSD17B5 or AKR1C3 as listed in the Hugo Database) was almost confined to ZR of human adrenals throughout development. HSD17B5 immunoreactivity in ZR became discernible and increased from around 9 years of age. Results of our present study support the theory of age-dependent adrenocortical cell migration and also indicated that ZR development is not only associated with adrenarche, but may play important roles in an initiation of puberty.

Structural reorganization of the adrenal cortex in OXYS rats during ontogeny.

Study of the structural reorganization of the adrenal cortex in OXYS and Wistar rats during aging showed that age-associated reorganization of the adrenal cortex in these rats consisted in atrophy, particularly pronounced in OXYS rats. Age-specific changes in the architectonics of the organ were noted mainly in the zona glomeruloza and zona fasciculata. The vessel-parenchyma relationships play the key role in the spatial reorganization of the adrenal cortex in OXYS and Wistar rats. The volume density of the sinusoidal capillaries in the zona fasciculata and zona reticularis increases during the late ontogeny, particularly so in Wistar rats, causing, in turn, an increase of the stroma/parenchyma volume proportion.

A morphometric study of the adrenal cortex of the female DDD mouse.

The aim of this study was to determine whether the thickness of the adrenocortical zone is associated with age in virgin and parous female DDD mice. The zona reticularis and zona glomerulosa of parous mice tended to be thicker than those of virgin mice at all ages. The zona fasciculata lactating parous mice was significantly thicker than that of virgin mice at 20 weeks of age (P<0.01). Age did not affect the thickness of the three outer adrenocortical zones in either group. However, in virgin mice, the X zone consisted of vacuolated and nonvacuolated cells at 5 weeks of age and only of vacuolated cells at 10 weeks of age; the number of vacuolated cells and the thickness of the zone decreased at 40 weeks of age. In contrast, parous mice of all ages lacked an X zone. The decrease in X zone thickness with age was most evident when expressed relative to organ weight. In conclusion, the thickness of the outer three adrenocortical zones is affected by endocrine changes associated with pregnancy and lactation but not by age. The thickness of the X zone is an index of growth and maturation in nulliparous female DDD mice less than one year of age.

Adrenal changes associated with adrenarche.

The mechanisms causing the rise in adrenal androgen production during the course of adrenarche remain to be defined. However, the increase in steroid release is clearly associated with a series of intra-adrenal changes in the expression of steroidogenic enzymes needed for dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) production, as well as an expansion of the adrenal zona reticularis (ZR). We and others have defined the adrenal expression pattern of key steroidogenic enzymes during adrenarche. As adrenarche proceeds, the expanding ZR expresses greater levels of cytochrome b5 (CYB5) and steroid sulfotransferase (SULT2A1) than the adjacent fasciculata. In contrast, the growing ZR is deficient in 3beta-hydroxysteroid dehydrogenase type 2 (HSD3B2). The resulting profile of steroidogenic enzymes lends itself to the production of adrenal androgens and appears to track the progression of adrenarche. This article reviews the intra-adrenal changes of the adrenal cortex associated with adrenarche.

Lesions of the adrenal cortex.

CONTEXT: In surgical pathology practice adrenal cortical tumors are rare. However, in autopsy series adrenal cortical nodules are found frequently. These are now being identified more commonly in life when the abdomen is scanned for other disease. It is important to differentiate between benign and malignant lesions as adrenal cortical carcinoma is an aggressive tumor. Molecular genetic investigations are providing new information on both pathogenesis of adrenal tumors and basic adrenal development and physiology. OBJECTIVE: To provide an overview of current knowledge on adrenal cortical development and structure that informs our understanding of genetic diseases of the adrenal cortex and adrenal cortical tumors. DATA SOURCES: Literature review using PubMed via the Endnote bibliography tool. CONCLUSIONS: The understanding of basic developmental and physiologic processes permits a better understanding of diseases of the adrenal cortex. The information coming from investigation of the molecular pathology of adrenal cortical tumors is beginning to provide additional tests for the assessment of malignant potential in diagnosis but the mainstay remains traditional histologic analysis.