The effect of long-term exposure to combinations of growth promoters in Long Evans rats: part 1: Endocrine adrenal function.

UNLABELLED: The aim of the study was to investigate whether the chronic administration (45 days) of clenbuterol (CB) at a growth promoting dose (1 mg kg(-1) bw) and/or dexamethasone (DEX: 0.1 mg kg(-1) bw) may cause the disruption of rat endocrine adrenal function. Blood samples were taken weekly during the whole experiment (S0-S7), and at different days of withdrawal (W0, W5, W10, W15 and W20). Hormone profiles were determined by RIA (ACTH) or EIA (corticosterone and catecholamines). ACTH showed significantly elevated concentrations from S1 until W5 (p<0.05) with CB administration. It began to decrease the day of DEX and CB-DEX administration. DEX showed significantly lowered ACTH concentrations from the day of drug injection (p<0.05). Corticosterone showed significantly elevated levels until W10 (p<0.01) with CB and CB+DEX. DEX showed lowered levels of corticosterone during the whole withdrawal period. Epinephrine presented significantly elevated plasma levels until W5 with CB and CB+DEX. With DEX, epinephrine was also elevated from W5 to W15 (p<0.05). Norepinephrine also presented significantly elevated plasma levels until S7 with CB and CB+DEX (p<0.001). With DEX no differences were found. CONCLUSION: Long-term administration of CB and/or DEX causes an endocrine adrenal disruption with changes in ACTH, glucocorticoid and catecholamine secretion.

The effect of long-term exposure to combinations of growth promoters in Long Evans rats: part 2. Adrenal morphology (histopathology and immunochemical studies).

The aim of the study was to investigate the effects of long-term exposure (45 days) to growth promoters: clenbuterol (CB: 1 mg kg(-1) bw) and/or dexamethasone (DEX: 0.1 mg kg(-1) bw), in adrenal gland morphology, and the possibility of recovery after the withdrawal of drug treatment. Animals were sacrificed at different days of withdrawal (W0, W5, W10, W15 and W20), and adrenal glands processed for histopathology and immunohistochemistry. Adrenals of CB treatment showed typical features of long-term administration of beta-agonists at W0 such as capillary dilatation in the fasciculata-reticularis zone, and this feature was also presented at W20. Adrenals of CB+DEX treatments showed the same results of CB treatment at days W0 and W20. However, DEX treatment presented the typical results of the exposure to corticoids with the atrophy of adrenal cortex. Immunohistochemistry of adrenal cortex steroidogenic enzymes (P450: scc, 3beta-HSD, aromatase) denoted that neither positive staining nor localization was affected by treatments. Aromatase enzyme was immunolocalized in adrenal medulla cells in controls as well as in treated groups. The immunolocalization of glucocorticoid receptors showed an increase in CB (+++) and CB+DEX (++) treatments compared to the control group (0) and DEX treatment (0). Histopathological and immunohistochemical results are closely related to those found for adrenal endocrine function. We can conclude that chronic administration of growth promoters influence adrenal morphology and glucocorticoid receptor expression.