Opposite effects of dexamethasone and ACTH on the adrenal cortex response to ethane dimethanesulphonate (EDS).

Recently we have reported that ethane dimethane-sulphonate (EDS), the Leydig cell cytotoxin, caused marked atrophy of the adrenal cortex of adult male rats. The aim of this work was to examine whether a 9-day treatment with dexamethasone (0.25 mg/kg/d) or ACTH (40 IU/kg/d), which started 4 days prior to administration of a single dose of EDS (75 mg/kg), influenced the response of the inner adrenocortical zones to the toxin. On day 15 after administration of EDS, adrenal weight was significantly decreased in saline treated rats, but glandular and serum corticosterone levels were not altered. In dexamethasone-suppressed rats, the effect of EDS was augmented; an additional decrease in adrenal weight was accompanied by reduced adrenal and serum corticosterone levels. In ACTH-treated animals EDS was ineffective. These results demonstrate that the deleterious effects of EDS on rat adrenal cortex can be prevented by ACTH and potentiated by dexamethasone.

beta-Adrenergic receptor manipulation and acid phosphatase and zinc levels in the ventral prostate of the adult rat.

The influence of 15-day treatments with the beta-adrenergic receptor agonist isoproterenol (120 micrograms/kg/d) or the antagonist propranolol (1.00 mg/kg/d) on acid phosphatase and zinc levels in the ventral prostate was examined in intact rats, rats simultaneously injected with dexamethasone (0.25 mg/kg/d) and animals chemically castrated with a single dose of ethane dimethanesulphonate (75 mg/kg). Isoproterenol-treatment significantly increased acid phosphatase concentration in the ventral prostate of intact rats, whereas propranolol prevented a glandular zinc loss induced by dexamethasone administration. These results demonstrate that the levels of both biochemical parameters in the prostate can be altered by beta-adrenergic receptor manipulation. The responsiveness of the two secretory processes is different and depends on the functional status of the ventral prostate.

The influence of dexamethasone treatment of pregnant rats on the development of chromaffin tissue in their offspring during the fetal and neonatal period.

The aim of these examinations was to determine the influence of dexamethasone (Dx)-treatment of gravid females, on day 16 of gestation on the development of medullary chromaffin tissue of their fetuses and neonatal offspring. In conducting these investigations we used stereological as well as spectrofluorimetric measurements, in 20-day-old fetuses and 1-, 3-, 5-, 7-, 9-, 11-, 13- and 14-day-old neonatal rats. Single Dx-treatment (1.5 mg/kg bw) of the dams led to a significant decrease in body and adrenal weight of their fetuses and neonatal offspring, and also reduction of the medullary volume and the number of chromaffin cells during the entire period examined as a result of decreased cell proliferation in the fetal and early neonatal period (till the 5th day of age). The proliferative activity of the chromaffin cells was evaluated through the mitotic index after applying the cytostatic vincristine-sulphate. During the second neonatal week the mitotic index showed significantly higher values in comparison with the corresponding controls, which indicates that there is regeneration and recovery of the adrenal gland medulla. Adrenaline content in the adrenal gland tissue of offspring of Dx-treated dams was significantly reduced only on the 1st neonatal day. Thus, the change in blood glucocorticoid level of pregnant females after a single Dx injection during the period critical for development of the hypothalamo-pituitary-adrenal system in fetuses affects the development and kinetics of medullar chromaffin cell division.

Ventral prostate structure and serum testosterone levels after chronic treatment with isoproterenol in adult rats with different androgen status.

The effects of chronic administration of the beta-adrenergic agonist isoproterenol (ISO) (120 microg/kg per day; subcutaneously) on the ventral prostate structure and serum testosterone concentrations were examined in adult rats with different androgen status: intact, intact testosterone-injected (1 mg/rat), surgically and chemically castrated rats. Chemical castration was evoked by an intraperitoneal injection of ethane dimethanesulfonate (EDS) (75 mg/kg). A ventral prostate response was only observed in intact and chemically castrated animals. Stereological analysis revealed atrophic changes in the glandular compartment of the prostate of ISO-treated intact rats, but they were probably the consequence of significantly decreased serum testosterone levels. In addition, in these animals alterations were found in the morphometrical parameters of the ventral prostate blood vessels, their relative and total volumes being increased. In chemically castrated rats, administration of ISO from the day of EDS application partially prevented the postcastrational regression of the ventral prostate without affecting blood testosterone level. However, it seems that the discharge of glandular secretion was attenuated at the same time. These results show that chronic treatment with ISO may have both stimulatory and inhibitory effects on the rat ventral prostate depending on the androgen status of the animals and, accordingly, on the site of ISO-action.

Treatment of pregnant females with dexamethasone influences postnatal development of the adrenal medulla.

In the light of the mutual dependence between the adrenal cortex and medulla, the aim of this work was to examine whether glucocorticoid treatment of pregnant rats affects the development of the adrenal medulla of their offspring in the postnatal period. Pregnant rats were treated with dexamethasone (Dx) in a daily dose of 0.3 mg Dx/kg b.w. during days 16-20 of gestation. The structure and function of the adrenal medulla of their 14-day-old offspring were estimated on the basis of the morphometric parameters of the gland, chromaffin cell mitotic index and adrenal gland adrenaline content. Stereological analysis was carried out at the light microscopic level, the mitotic index was determined by counting the number of metaphase arrested chromaffin cells following the administration of vincristine-sulphate, whereas adrenaline content in the adrenal gland was measured fluorimetrically. Plasma ACTH concentrations of the offspring were also determined by RIA. Long term Dx treatment of pregnant rats caused a significant decrease of the total volume of adrenal chromaffin tissue in the 14-day-old offspring as well as a reduction in the number of chromaffin cells and the average cell and nuclear volumes. The proliferative activity of the chromaffin cells was also lower than in the control offspring. These changes were accompanied by a significantly reduced adrenaline content in the adrenals. The results of this work show that glucocorticoid excess during the period of pregnancy when the fetal adrenal medulla is formed has a strong inhibitory effect on the adrenal medulla of the offspring at the age of 14 days.

The influence of prolonged dexamethasone treatment of pregnant rats on the perinatal development of the adrenal gland of their offspring.

The effects of prolonged dexamethasone (Dx) administration to pregnant rats on the structure and function of the adrenal glands of fetal and neonatal offspring have been investigated by combined stereological and ultrastructural methods, as well as by metaphase index determination. Pregnant rats were injected subcutaneously with Dx (0.3 mg/kg body weight/day) during 5 days, starting from day 16 of gestation. The dams and their fetuses were killed 24 hr after the last injection. The neonatal offspring were killed in the same way on the 3rd and 14th day of life. Because in fetal and 3-day-old neonatal rats zona reticularis (ZR) was poorly defined and could not be clearly seen as a separate zone, zona fasciculata (ZF) and ZR were analyzed as one, inner zone (IZ). In 14-day-old rats ZF and ZR were analyzed separately. Proliferative activity of adrenocortical cells was estimated following the application of Vincristine sulphate. Dx treatment of pregnant rats induced a marked decrease of fetal adrenal gland volume and the volumes of zona glomerulosa + capsula (ZG + C) and IZ as the consequence of atrophic changes in the gland and reduction of the average volume and total number of adrenocortical cells. Similar morphometric changes were found in 3- and 14-day-old pups. However, in 3-day-old animals the number of cortical cells in the ZG was increased, whereas on the 14th postnatal day cortical cell number remained decreased only in the ZF. The multinuclear giant cells, numerous lymphocytes, and the resorption zones, present in the adrenal cortex of fetuses and 3-day-old pups of both experimental and control dams, were not seen in 14-day-old offspring. These results demonstrate that prolonged treatment of pregnant rats with Dx in the period when intensive differentiation of the fetal hypothalamo-hypophyseal system takes place inhibits proliferative activity of adrenocortical cells and evokes considerable atrophic changes in the adrenal glands of offspring from 20 days gestation to 14 days after birth. The histological appearance of the adrenal cortex and the ultrastructure of adrenocortical cells suggest that cortical cell function was inhibited.

Effects of ethane dimethanesulfonate on the structure of adult male rat adrenal cortex.

The influence of ethane dimethanesulfonate (EDS), a specific toxicant for Leydig cells, on the morphometric characteristic of adult male rat adrenal cortex was examined on day 15 after administration. As expected, the dose of 75 mg kg-1 of EDS produced drastic reduction in serum testosterone levels followed by a decrease in testis and seminal vesicle weight. However, a considerable drop (over 50%) in adrenal weight was also found. Stereological analysis of the adrenal cortex, performed under light microscope, revealed atrophy of all adrenocortical zones. The changes were most prominent in the inner zones. Thus, in the zona fasciculata the number of parenchymal cells was markedly decreased. In the zona reticularis a layer consisting mostly of atrophic parenchymal cells was localised at the border between zona reticularis and zona fasciculata. The remaining small number of cortical cells in this zone displayed a notable hypertrophy. It is concluded that EDS at a dose that destroys Leydig cells has a strong deleterious effect on steroidogenic cells of adult male rat adrenal cortex.

Detection of perforin and tumour necrosis factor alpha mRNA expressing cells in sclerosing lymphocytic lobulitis of the breast.

The contribution of a cellular immune response to tissue destruction in sclerosing lymphocytic lobulitis of the breast is not well understood. In this study, comparison of one case with two age matched control cases showed an increased frequency of activated perforin mRNA expressing cells at the site of tissue destruction in lobulitis. Along with the detection of tumour necrosis factor alpha (TNF alpha) mRNA expressing cells in the infiltrates, the striking association of perforin expressing activated cytotoxic cells with remaining gland parenchyma and the high level of perforin mRNA suggests activation of cytotoxic cells in situ. These findings are evidence that cell mediated cytotoxicity plays a significant role in the destruction of mammary gland tissue in sclerosing lymphocytic lobulitis.

The effect of dexamethasone on the adrenal gland in fetal and neonatal rats.

The development and regeneration of the adrenal glands were examined by stereological and morphological methods in 20-day-old fetal, as well as 3-day- and 14-day-old neonatal male rats born to dams treated with dexamethasone (Dx) on day 16 of gestation. In the fetuses and 3-day-old rats, zona fasciculata (ZF) and zona reticularis (ZR) were analyzed as one inner zone (IZ), while in 14-day-old animals they were analyzed separately. Single Dx treatment (1.5 mg/kg b.w.) of the dams led to atrophic changes in the adrenal cortex of the fetuses. These changes were visible to a certain degree up to the 14th neonatal day. Administration of Dx to pregnant rats induced a significant decrease of both adrenal weight and volume, as well as the volume of zona glomerulosa + capsule (ZG + C) and IZ, both in fetuses and 3-day-old rats. This was due to a decrease in the number but not the volume of cortical cells. Also, necrotic cortical cells, infiltrations and resorption zones accompanied by the presence of macrophages, giant cells and lymphocytes were observed. In 14-day-old animals, the degree of atrophic changes in the adrenal cortex was reduced. Changes were observed only in ZR which was decreased in volume resulting from both a significant decrease of the volume and number of cortical cells. Then number of macrophages was somewhat increased, while giant cells were not present. However, the total number of parenchyma cells in ZG was increased, pointing to the possibility of renewal of cortical cells within this zone. The results of the present study demonstrate that even a single Dx dose given to pregnant rat during the period critical for the development of the hypothalamo-pituitary-adrenal system in the fetuses leads to marked changes in the structure and function of the fetal adrenal glands which are partially maintained up to the 14th day of postnatal life.

Mitotic activity and cell deletion in ventral prostate epithelium of intact and castrated oxytocin-treated rats.

Previous study has shown that oxytocin (OT) attenuated the postcastration regression of ventral prostate epithelium in rats. To decide if this effect is associated with stimulation of cell division or improvement of cell survival, metaphase index of secretory cells and frequency of apoptotic bodies in the epithelium, combined with stereological parameters, were determined in the present study. OT was injected subcutaneously in a dose of 0.25 IU/100 g/d during 5 postorchiectomal days and the same treatment was applied to intact rats. Only the prostate of castrated animals responded to OT. They had greater total volume of the epithelium, total number and metaphase index of secretory cells, but lower frequency of apoptotic bodies. These findings demonstrate the ability of OT to stimulate mitotic activity and to diminish mortality of secretory cells caused by orchiectomy.

The response of rat adrenal zona fasciculata and zona reticularis to oxytocin treatment.

The response of the adrenal zona fasciculata (ZF) and zona reticularis (ZR) to oxytocin (OT) was examined in male rats using a stereological method. The 10-day administration of 0.25 IU OT/100 g daily caused an enlargement of ZF due to cell hypertrophy associated with striking lipid accumulation. The volume of ZR was decreased, this change being the consequence of the reduced cell population. The possible site of OT action is discussed.

Stereologic analysis of ventral prostate of oxytocin-treated rats.

Ventral prostate response to oxytocin (OT) was examined in intact and castrated adult rats. The treatment consisted of 10 daily subcutaneous injections of 0.25 IU OT per 100 g body weight, which for orchiectomized rats began immediately after surgery. OT induced prostatic response only in castrated animals. Stereologic analysis revealed changes in the epithelial component, its total volume and surface being increased. The acinar lumen as well as the glandular weight were also enhanced. A possibility that the ventral prostate is the target organ for OT is discussed.

The response of rat adrenal medulla to oxytocin.

Effects of oxytocin (OT) on the adrenal chromaffin tissue of male rats were examined by coupled morphometric and biochemical techniques. Synthetic OT was administered in doses of 0.14 and 0.25 IU/100 g/d during 7 or 10 consecutive days and the effects were followed 1, 24, 72 and 168 hours after the last injection. The function and structure of chromaffin cells were affected by the higher dose of OT only. They caused divergent responses on their amine contents. Adrenaline, noradrenaline and dopamine contents were increased, while serotonin content was decreased. These changes were different in duration and time of incidence. Stereological analysis showed an enhanced number of chromaffin cells and an increase in their total volume. The parallelism between the changes in chromaffin cell number and the catecholamine content strongly suggests a mitogenic effect of the applied OT.

[Incorporation of 3H-cortisol into the dental pulp and the induced changes]. / Incorporation du 3H-cortisole dans la pulpe dentaire et changements induits.

The incorporation of labelled hydrocortisone (3H-cortisol) in the dental pulp of Wistar rats has been tested using autoradiography. Light microscopy showed that an hour after injection the hormone is incorporated in the nuclei of the odontoblasts, subodontoblastic and endothelial cells of the dental pulp. It was also demonstrated at the ultrastructural level that a 4 week-treatment with high rates of hydrocortisone (16 and 32 mg/kg) at the time of rat intensive growth induces degeneration of the odontoblasts, pulp connective tissue cells and capillaries. High rates of hydrocortisone thus induces a decrease in the protective and reparative responses of rat molar pulp.

Influence of maternal adrenalectomy on the ultrastructure of the adrenal gland in neonatal rats.

Maternal adrenalectomy at 7 or 14 days of gestation produced increased cell necrosis within zona reticularis cells on the day of birth and at 24 or 48 h after birth. Small remnants or large portions of adrenocortical cells were present within macrophages. In otherwise normal adrenocortical cells, lipid droplets were incorporated within some mitochondria. Autophagocytosis of single mitochondria was observed within adrenocortical cells. Undoubtedly ultrastructural changes represent stimulation of adrenocortical cells in neonatal rats in response to maternal adrenalectomy.

Adrenocorticotropic (ACTH) cells of rats after head irradiation.

The heads of intact rats and of rats 15 days after adrenalectomy were irradiated with 1200 R. Some of the adrenalectomized animals with irradiated heads were treated with 5 mg of deoxycorticosterone acetate. In adrenocorticotropic cells of adrenalectomized rats 15 and 30 days after irradiation, the decreased amount of the granular endoplasmic reticulum and the Golgi regression imply a considerably decreased protein synthesis. The finding of an increased number of granules and of granules larger than normal suggests that they are the result of slowed down transport and secretion of the products of these cells' activities. After head irradiation an increased number of degenerative cells was evident in the pituitary of both intact and adrenalectomized rats. The degree of the degenerative changes and the number of degenerative cells was higher 30 than 15 days after irradiation and both were decreased if the adrenalectomized rats were treated with deoxycorticosterone acetate.