Mechanisms of Suppression of Epinephrine Production in Rats by Low-Dose Developmental Exposure to DDT.

We studied the mechanisms underlying decreased production of epinephrine by adrenal glands in rats developmentally exposed to endocrine disruptor DDT was performed on the basis of assessment of morphology, fine structure, and function of the adrenal medulla and medullary cells. It was found that the main mechanisms of disruptive action of DDT leading to a decrease in epinephrine secretion into systemic circulation are a decrease in the growth rate of the adrenal medulla, a decrease in the number of mitochondria in adrenal cells, especially under the outer cytoplasmic membrane, destructive changes in mitochondria, and a progressive decrease in the synthesis of tyrosine hydroxylase. The decrease in the number of mitochondria and suppression tyrosine hydroxylase synthesis in adrenal cells predominate during the pubertal period, while slowdown of the growth of the adrenal medulla and progressive decrease in the synthesis of tyrosine hydroxylase seem to be the most evident mechanisms after puberty.

Low-Dose Exposure to Endocrine Disruptor Dichlorodiphenyltrichloroethane (DDT) Affects Transcriptional Regulation of Adrenal Zona Reticularis in Male Rats.

The study examined transcriptional regulation of adrenal zona reticularis development in male Wistar rats exposed to low doses of endocrine disruptor dichlorodiphenyltrichloroethane (DDT) prenatally and postnatally. At pubertal age, zona reticularis demonstrated a retarded growth with a low proliferative activity of its cells. At this age, zona reticularis was characterized with overexpression of ß-catenin by steroid-producing cells; a high percentage of cells with membrane and cytoplasmic localization of ß-catenin, and reduced number of cells with nuclear ß-catenin attesting to insufficient activation of Wnt signaling. Expression of transcriptional factor Oct4 by reticularis cells was down-regulated indicating their diminished proliferative potency. No significant alterations in Sonic Hedgehog expression were observed. Thus, DDT-provoked disorders of transcriptional regulation result in abnormal development of zona reticularis thereby disturbing sexual maturation in males.

Ultrastructural Mechanisms of Impaired Aldosterone Synthesis in Rats Exposed to DDT during Prenatal and Postnatal Development.

The study is aimed at elucidation of ultrastructural mechanisms underlying impaired aldosterone synthesis by glomerulosa cells in Wistar rats exposed to low doses of endocrine disrupter DDT during prenatal and postnatal development. Analysis of rat zona glomerulosa histology and function during the pubertal and postpubertal periods showed that exposure to endocrine disrupter DDT disturbs its development and reduced the production of aldosterone. Electron microscopy showed that changes in the aldosterone synthesis are related to impaired reorganization of the mitochondrial apparatus, one of the leading factors in the regulation of steroidogenesis, in glomerulosa cells in DDT-exposed rats during puberty.

Changes in Histophysiology of the Adrenal Medulla in Rats after Prenatal and Postnatal Exposure to Endocrine Disruptor DDT.

We studied histophysiology of the adrenal medulla in adult (70-day-old) male Wistar rats developmentally exposed to low doses of endocrine disruptor DDT. It was found that exposure to DDT during the prenatal and postnatal ontogeny decelerated the development of the adrenal medulla and reduced the synthesis of tyrosine hydroxylase, the rate-liming enzyme of catecholamine synthesis, in chromaffin cells, which led to a decrease in epinephrine secretion into the blood.

Application of Focal Photoinduced Thrombosis for Modeling Spinal Cord Ischemia.

Typical ischemic damage to neurons were detected in the focus of experimental photothrombosis and in the transition zone. They were associated with symptoms of impaired motor functions and dysfunction of pelvic organs. The applied method of focal photothrombosis can be used for simulation of spinal cord ischemia for the development of methods for pharmacological correction and restoration of impaired sensorimotor functions.

Morphological and Cytophysiological Changes in the Adult Rat Adrenal Medulla after Prenatal and Postnatal Exposure to Endocrine-Disrupting DDT.

The aim of the investigation was to study morphological and cytophysiological changes in the adult rat adrenal medulla after prenatal and postnatal exposure to endocrine-disrupting chemical dichlorodiphenyltrichloroethane (DDT). MATERIALS AND METHODS: The experiment was carried out on male Wistar rats (n=30). The rats were exposed to low doses of DDT during prenatal and postnatal development (n=10) and during postnatal development (n=10) only. The average daily intake of DDT by rats was 3.30±0.14 µg/kg. The control (n=10) and experimental animals were sacrificed at the age of 10 weeks (post-puberty), when rat adrenal glands reached their maximum development. Histological samples of the equatorial sections of the adrenal glands were prepared. The adrenal medulla was studied using light microscopy and computer morphometry. Immunohistochemistry was performed to evaluate tyrosine hydroxylase expression in chromaffin cells. Plasma epinephrine content was measured using enzyme-linked immunosorbent assay. RESULTS: Postnatal exposure of rats to low doses of the endocrine disruptor was found to interfere with adrenal medulla development and cytophysiology of chromaffin cells. Prenatal and postnatal exposure resulted in more profound delay in adrenal medulla development of adult rats as compared to the values of rats exposed postnatally, which was manifested by reduced area of the adrenal medulla and reduced total area of chromaffin cells in its section. Postnatal exposure is manifested by more significant functional disorders including decreased synthesis of tyrosine hydroxylase enzyme in the cytoplasm of chromaffin cells and elevated number of tyrosine-hydroxylase-negative cells in the medulla section, leading to a decrease in plasma epinephrine concentration. CONCLUSION: Exposure to low doses of DDT in the early stages of development leads to morphological and cytophysiological changes in the adult rat adrenal medulla and, therefore, reduced functional activity of chromaffin cells, which allows considering the endocrine disruptor DDT a potential risk factor disrupting the function of the neuroendocrine system.

Regulation of Proliferative Processes in Rat Adrenal Cortex by Transcriptional Factor PRH under Conditions of Developmental Exposure to Endocrine Disruptor DDT.

The effects of endocrine disrupters of transcriptional control of morphogenesis are poorly studied. Changes in the expression of transcriptional factor PRH and proliferation of adrenal cortical cells were analyzed in pubertal and postpubertal rats exposed prenatally and postnatally to low doses of endocrine disrupter DDT. In rats exposed to DDT, the expression of PRH and proliferation of adrenal cortical cells differed from those in control rats. Association between these parameters was weakened in the zona glomerulosa and zona reticularis and was absent in the zona fasciculata. These findings suggest that exposure to DDT in pre- and postnatal periods impairs the regulation of proliferative processes by transcriptional factor PRH in all zones of rat adrenal cortex, which can be a mechanism of the disruptive action of DDT.

Changes in Secretory Activity of Adrenal Zona Fasciculata Cells in Pubertal Rats Exposed to Low Doses of DDT in Different Periods of Ontogeny.

We studied secretory activity of adrenal zona fasciculata cells in pubertal rats exposed to low doses of endocrine disrupter DDT during prenatal and postnatal periods and only during postnatal period. In exposed animals, circulatory disturbances leading to degeneration and necrosis of cells as well as regeneration foci were revealed in the outer zona fasciculata. In rats exposed to DDT during the prenatal and postnatal periods, compensatory increase in secretory activity of cells due to increase in mitochondria content was noted in the inner zona fasciculata, which determined elevated serum concentration of corticosterone. In rats exposed to DDT only during the postnatal development, functional activity of zona fasciculata cells was suppressed, which attested to delayed upregulation of secretion.

Expression of Transcription Factor PRH/Hhex in Adrenal Chromaffin Cells in the Postnatal Development and Its Role in the Regulation of Proliferative Processes.

Transcription factor PRH/Hhex suppresses cell proliferation and contributes to regulation of prenatal and postnatal ontogeny. Neurons of the peripheral nervous system and chromaffin cells were previously considered as non-expressing PRH/Hhex in postnatal development. In our study, the expression of PRH/Hhex in chromaffin cells of rat adrenal glands and association between the decrease of proliferation and activation of PRH/Hhex expression were demonstrated.

Changes in Canonical ß-Catenin/Wnt Signaling Activation in the Adrenal Cortex of Rats Exposed to Endocrine Disruptor Dichlorodiphenyltrichloroethane (DDT) during Prenatal and Postnatal Ontogeny.

Prenatal and postnatal exposure to low doses of the endocrine disruptor dichlorodiphenyltrichloroethane (DDT) leads to delayed activation of the canonical ß-catenin/Wnt signaling in zona glomerulosa and zona reticularis of the adrenal cortex in rats, which changed the rate of their postnatal development. Suppression of the Wnt pathway in zona fasciculata promotes its regeneration after DDT-induced blood circulation disorders and cell death.

[Differences in adrenal steroid hormones production in pubertal rats exposed to low doses of endocrine disruptor DDT during prenatal and postnatal development]. / Osobennosti produktsii steroidnykh gormonov nadpochechnikov v pubertatnom periode u krys, podvergavshikhsia vozdeistviiu nizkikh doz éndokrinnogo disraptora DDT v prenatal'nom i postnatal'nom razvitii.

Production of adrenal steroid hormones in pubertal male Wistar rats exposed to low doses of DDT during both prenatal and postnatal and only postnatal development was evaluated. Altered production of all types of steroid hormones and serum steroid profile with opposite changes in rats exposed prenatally and postnatally, and only postnatally was found. The study showed that daily exposure to low doses of DDT enhanced conversion of progesterone to 17OH-progesterone and did not exert selective antiandrogenic or proestrogenic action unlike effect of toxic and subtoxic doses. Impaired morphogenesis of the adrenal cortex and circulatory disorders in zona glomerulosa contributed to reduced aldosterone and sex steroid hormones production.

Effect of Prenatal and Postnatal Exposure to Low Doses of DDT on Catecholamine Secretion in Rats in Different Period of Ontogeny.

We studied the effects of prenatal and postnatal exposure to low doses of DDT on secretion of basic catecholamines epinephrine and norepinephrine in pubertal and adult rats. It was found that the endocrine-disrupting chemical under study led to a progressive decrease in the content of epinephrine and especially norepinephrine in systemic circulation, which indicated their disturbed secretion by the adrenal medulla and sympathetic nervous system cells. In animals exposed to low doses of DDT in both pre- and postnatal periods, the decrease in catecholamine secretion after puberty was less pronounced than in animals exposed only during the postnatal period, which can indicate the development of compensatory processes.

[Alteration of rat adrenal cortex after low-dose exposure to endocrine disrupting chemical dichlorodiphenyltrichloroethane since the first day of postnatal development].

The purpose of the present study was to examine morphological and functional alterations in adrenal cortex of rats exposed to low doses of DDT since the first day of postnatal development till puberty. Daily consumption of DDT was 3.71±0.15 µg/kg bw. This level of exposure corresponds with human daily intake of DDT with food products according to maximum permissive levels of food contamination. Production of steroid hormones of the adrenal cortex was evaluated by quantification of aldosterone, corticosterone, estradiol, and estronе serum levels by enzyme-linked immunosorbent assay. Organometry and light microscopy of the adrenal glands were performed. After six weeks of exposure serum concentration of aldosterone was elevated by 50% in average, estradiol - by 25%, estrone - by 29%, but serum level of corticosterone was decreased by 53% compared to the control values. The adrenal glands had decreased weight and reduced cortex width from 897.75±23.31 to 776.25±19.91 µm mainly due to narrowing of reticularis zona by 11.35%. Histological examination also found proportional increase of cell number in mm2 of reticularis zona and therefore found no differences in total endocrine cell count in reticularis zona between the control (14 085.94±704.30) and DDT exposed rats (13 678.20±410.34). Light microscopy revealed hemorrhages between glomerulosa zona and fasciculata zona as well as fasciculate zona and reticularis zona, foci of discomplexity in fasciculate zona, dystrophy and decreased size of fasculata cells. The data obtained demonstrated that low-dose exposure to DDT during postnatal development led to obvious changes in morphology and function of rat adrenal gland. Low doses of DDT disrupt steroid hormone production by all layers of adrenal cortex in puberty. The results show that very low-dose exposure to DDT needs further investigations, and safety of maximum permissible levels of DDT and other endocrine disrupting chemicals in food products should be reassessed.

[Regulation of hair follicle cycle].

This review is devoted to the control of hair growth. The hair follicle undergoes cyclic transformation from the resting phase (telogen) to the growth phase (anagen). The latter phase is characterized by rapid proliferation of follicular keratinocytes and elongation and thickening of the hair shaft. The regression phase (catagen) leads to the involution of the hair follicle. These cyclic changes include rapid remodeling of both the epithelial and the dermal components. They are controlled by numerous different factors: sex hormones, neurotrophins, FGF, TGF, BMP, VEGF, Sonic Hedgehog, and other signaling pathways.

[Histophysiology of the epidermis].

This literature review summarizes the data on the general principles of the structure and functions of keratinocytes, melanocytes, dendritic cells (DC) and tactile epithelial cells. Special attention is paid to the process of keratinization, the formation of lipid barrier of the stratum corneum. The problem of the stem and transitional cell surface markers is discussed. Detailed current data are presented on the structure and functions of keratinosomes, their participation in the process of desquamation and the formation of intercellular cement, forming the basis of polar lipids. It is shown that lipid profile of the intercellular space of the stratum corneum is changing in the direction of the surface of the epidermis. Considerable part of the review is devoted to the data demonstrating the functions of keratinocytes: synthesis of mitogens, chemokines that attract DC and T-lymphocytes to the epidermis; production of antimicrobial peptides. In this report, the questions are discussed of the existence of two types of tactile epitheliocytes, of the participation of DC in the process of keratinization, on the transfer of information on an antigen to T-lymphocytes. The data are presented on the participation of melanocytes in the protective function of the epidermis.

Standardized and extended catalog of major proteins of the human kidney.

A new version of a two-dimensional electrophoretic catalog of proteins of the human kidney and of various morphological and functional structures of the human kidney is presented; it contains information about 179 polypeptides. The following proteins were identified: crystallin, albumin, mitochondrial superoxide dismutase, actin, fatty acid-binding protein, alpha-ATP-synthase, and transferrin. Some protein groups are specific for certain morphological structures.