Ru-Lian Hsu

Chronic Effects of Propylthiouracil on Metabolism and Secretion of Adrenocorticotropin and Corticosterone in Male Rats

Background: Propylthiouracil (PTU) is a thioamide drug for treating hyperthyroidism. We have already found that chronic administration of PTU decreases the level of plasma corticosterone and attenuates both the activities of 11β- hydroxylase and the generation of cyclic adenosine monophosphate (cyclic AMP) in rat zona fasciculata-reticularis (ZFR) cells. The present study aimed to investigate the chronic effects of PTU on metabolism, adrenocorticotropic hormone (ACTH) and corticosterone secretion. Methods: Male rats were randomly divided into four groups and injected subcutaneously with saline, PTU, thyroxine (T4) or PTU plus T4 once daily for 2 weeks. For metabolism studies, the body weight, food intake, water intake, urine volume, and feces weight of every rat were recorded daily. The rats were sacrificed after treatment, and the plasma thyroid stimulating hormone (TSH), ACTH, and corticosterone were measured. ZFR cells were separated from adrenal glands and then stimulated by forskolin (an activator of adenylyl cyclase, 10^(-5) M), 8-bromo-cAMP (8-Br-cAMP, a permeable analogue of cAMP, 10^(-5) M), ACTH (a stimulator to increase corticosterone secretion, 10^(-9) M), and deoxycorticosterone (DOC, a steroidogenic precursor of corticosterone, 10^(-5) M) in order to investigate the alternation of corticosterone secretion and enzyme activity. Results: Chronic administration of PTU decreased food intake and feces weight but increased urine volume. The concentration of plasma TSH increased after chronic PTU treatment. PTU also suppressed release of ACTH and decreased production of corticosterone. After the isolation of ZFR cells from PTU and PTU plus T4-treated rats, both basal and evoked levels of corticosterone release were enhanced. Conclusion: Chronic administration of PTU inhibited pituitary gland from releasing ACTH, and this reaction led to decrease in corticosterone production in vivo. PTU treatment might upregulate downstream messengers of ACTH signal pathway in ZFR cells, thus enhancing release of corticosterone in vitro.