title: Effects of experimentally induced hyperthyroidism on central hypothalamic-pituitary-adrenal axis function in rats: in vitro and in situ studies.
abstract: Hyperthyroidism is associated with hypercorticosteronemia, although the locus that is principally responsible for the hypercorticosteronism remains unclear. The purpose of this study was to assess the effects of hyperthyroidism on the functional integrity of the hypothalamic-pituitary-adrenal (HPA) axis, to identify the locus in the HPA axis that is principally affected, and address the time-dependent effects of alterations in thyroid status. The functional integrity of each component of the HPA axis was examined in vitro and in situ in sham-thyroidectomized male Sprague-Dawley rats given placebo or in thyroidectomized rats given pharmacological dose (50 μg) of thyroxin for 7 or 60 days. Basal plasma corticosterone and corticosterone binding globulin (CBG) concentrations were significantly increased in short- and long-term hyperthyroid rats, and by 60 days. Basal plasma ACTH levels were similar to controls. Both hypothalamic CRH content and the magnitude of KCL- and arginine vasopressin (AVP)-induced CRH release from hypothalamic culture were increased in long-term hyperthyroid rats. There was a significant increase in the content of both ACTH and β-endorphin in the anterior pituitaries of both short- and long-term hyperthyroid animals. Short-term hyperthyroid rats showed a significant increase in basal POMC mRNA expression in the anterior pituitary, and chronically hyperthyroid animals showed increased stress-induced POMC mRNA expression. Adrenal cultures taken from short-term hyperthyroid rats responded to exogenous ACTH with an exaggerated corticosterone response, while those taken from 60-day hyperthyroid animals showed responses similar to controls. The findings show that hyperthyroidism is associated with hypercorticosteronemia and HPA axis dysfunction that becomes more pronounced as the duration of hyperthyroidism increases. The evidence suggests that experimentally induced hyperthyroidism is associated with central hyperactivity of the HPA axis.
authors.affiliation: Department of Anatomy, School of Medicine, University of Athens, 75 Mikras Asias Str., 11527 Goudi, Athens, Greece. elizabethojohnson@gmail.com
authors.forename: Elizabeth O
authors.initials: EO
authors.lastname: Johnson
authors.forename: Aldo E
authors.initials: AE
authors.lastname: Calogero
authors.forename: Maria
authors.initials: M
authors.lastname: Konstandi
authors.forename: Themis C
authors.initials: TC
authors.lastname: Kamilaris
authors.forename: Sandro
authors.initials: S
authors.lastname: La Vignera
authors.forename: Sandro La
authors.initials: SL
authors.lastname: Vignera
authors.forename: George P
authors.initials: GP
authors.lastname: Chrousos
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D006980:Hyperthyroidism / Q000503:physiopathology*; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism / Q000473:pathology*; D008297:Male; D010913:Pituitary-Adrenal System / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013963:Thyroid Hormones / Q000378:metabolism
chemical_list: D013963:Thyroid Hormones; D000324:Adrenocorticotropic Hormone