Effects of Short and Long Duration Hypothyroidism and Hyperthyroidism on the Plasma Adrenocorticotropin and Corticosterone Responses to Ovine Corticotropin-Releasing Hormone in Rats*

Abstract

We report here a study of the plasma ACTH and corticosterone responses to synthetic ovine CRH (oCRH) in hypothyroid and hyperthyroid rats studied 7, 15, and 60 days after either thyroidectomy or the administration of pharmacological doses of T4. The purpose of this study was to further clarify the time-dependent effects of alterations in thyroid status on the functional integrity of the hypothalamic-pituitary-adrenal axis and to aid in the interpretation of the oCRH stimulation test in hypo- and hyperthyroid states. Our data demonstrate that hypothyroid rats have a significant reduction in the cerebrospinal fluid (CSF) levels of corticosterone and a significant decrease in adrenal weight in association with significant increases in the plasma ACTH response to oCRH. On the other hand, the corticosterone response to the ACTH released during the oCRH stimulation test was significantly reduced in hypothyroidism. With increasing duration of thyroidectomy-induced hypothyroidism, there was a progressive fall in CSF corticosterone levels, a progressive increase in the plasma ACTH response to oCRH, and a gradual normalization of the corticosterone responses to the ACTH released during oCRH stimulation. Our findings in hyperthyroid rats were generally the converse of those seen in hypothyroidism. Hence, there was a significant increase in the CSF levels of corticosterone and a significant increase in adrenal weight in association with an initial slight decrease in the ACTH response to oCRH. On the other hand, the corticosterone response to the ACTH released during oCRH stimulation was significantly increased. There was a gradual increase in the magnitude of the rise in CSF corticosterone levels with time, as well as a gradual normalization of adrenocortical responses during oCRH stimulation. The ACTH plasma clearance rates were similar in hypo-, hyper-, and euthyroid rats. Our data do not permit definitive identification of the precise locus in the hypothalamic-pituitary-adrenal axis that is principally affected by experimentally induced alterations in thyroid status. However, these data are most compatible with a subtle hypothyroid-induced centrally mediated adrenal insufficiency and a subtle hyperthyroid-induced centrally mediated hypercortisolism. These data also suggest that alterations in hypothalamic-pituitary-adrenal function in states of disturbed thyroid function become somewhat more pronounced as the duration of thyroid dysfunction increases. The fact that pituitary-adrenal responses to oCRH are consistently altered in states of thyroid dysfunction may be relevant to the clinical interpretation of oCRH stimulation tests.(ABSTRACT TRUNCATED AT 400 WORDS)

Experimentally-induced hyperthyroidism is associated with activation of the rat hypothalamic–pituitary–adrenal axis

“…Our results showed, as early as 7 days after experimentally-induced hyperthyroidism, a slight attenuation in the ACTH response to ovine (o)CRH, in association with a significant augmentation of the corticosterone response to the ACTH released during CRH stimulation (2). These data were found most compatible with a subtle hyperthyroidism-induced centrally mediated hyperstimulation of the adrenals in rats with short-and longterm hyperthyroidism.…”

“…cannulae as previously described (2). Briefly, cannulae were prepared from a 35 cm length of polyethylene tubing (0.965 mm, od; 0.58 mm id; PE-50, Clay Adams, Pasippany, NJ, USA).…”

“…Basal plasma corticosteroid binding globulin (CBG) binding capacity was measured in euthyroid and hyperthyroid animals as previously described (2). Briefly, endogenous corticosterone was stripped and plasma was diluted 1:20 with 50 mM PBS.…”

“…CBG binding capacity was defined as total binding minus the nonspecific binding corrected to micrograms [3H]-corticosterone bound/dl rat plasma. Levels of IR-ACTH and IR-corticosterone were assessed in CSF as we have previously described (2). Briefly, rats were anesthetized [pentobarbital (55 mg/kg body weight (BW), i.p.)…”

Modulation of adult hippocampal neurogenesis by thyroid hormones: implications in depressive-like behavior

“…59,60 Plasma corticosterone was lower in hypothyroid rats than in euthyroid and TH-treated rats, in agreement with previous studies. 61 Since high levels of glucocorticoids inhibit neurogenesis, it is unlikely that the effects of TH are exerted by changes in corticosterone levels. Moreover, this relationship between thyroidal status and corticosterone levels also discards the possibility that the increased floating behavior observed in hypothyroid rats could have been induced by differences in adrenal function, since low levels of glucocorticoids are associated with reduced immobility in the forced swimming test and vice versa.…”