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.

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.

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.

Propranolol treatment affects ventral prostate blood vessels and serum testosterone concentrations in adult rats.

The influence of prolonged beta-adrenergic receptor blockade on stereologic parameters of the ventral prostate and serum testosterone concentrations was examined in adult rats injected with propranolol (0.1 or 0.4 mg kg-1/day) for 15 or 30 consecutive days. Both doses of propranolol reduced the relative and absolute volume of the ventral prostate blood vessels. This effect was prevented by simultaneous administration of urapidil, an alpha 1-adrenergic receptor antagonist, indicating that a compensatory vasoconstriction took place as a consequence of propranolol treatment. Serum testosterone concentration was significantly increased following the 30-day application of the lower dose of the drug. These results show that prolonged administration of propranolol, although not affecting the epithelial component of the gland, may indirectly influence prostatic function by reducing the blood flow to the gland.