Effects of short- and long-duration hypothyroidism on hypothalamic–pituitary–adrenal axis function in rats: In vitro and in situ studies

Abstract

The purpose of this study is to assess the effects of hypothyroidism on the hypothalamic-pituitary-adrenal (HPA) axis; the functional integrity of each component of the HPA axis was examined in short-term and long-term hypothyroidism. Neuropeptide synthesis, release, and content were evaluated in vitro both in the hypothalamus and anterior pituitary, and corticosterone release was assessed in primary adrenal cell cultures at 7 (short-term) and 60 days (long-term hypothyroidism) after thyroidectomy in male rats. Hypothyroid rats showed adrenal insufficiency in several parameters, which were associated with the duration of hypothyroidism. Cerebrospinal (CSF) ACTH was decreased in all hypothyroid animals, while CSF corticosterone levels were significantly decreased only in long-term hypothyroidism. Long-term hypothyroid animals showed decreased corticotropin-releasing hormone (CRH) mRNA expression in the hypothalamic paraventricular nucleus under both basal and stress conditions, decreased CRH release from hypothalamic organ cultures after KCL and arginine vasopressin stimulation, as well as an increased number of anterior pituitary CRH receptors. In contrast, short-term hypothyroid rats showed changes in anterior pituitary function with an increased responsiveness to CRH that was associated with an increase in CRH receptors. Although both short- and long-term hypothyroidism was associated with significant decreases in adrenal weights, only long-term hypothyroid rats showed changes in adrenal function with a significant decrease of ACTH-induced corticosterone release from cultured adrenal cells. The data suggest that long-term hypothyroidism is associated with adrenal insufficiency with abnormalities in all three components of the HPA axis. Short-term hypothyroidism, on the other hand, is associated with increased pituitary corticotroph responsiveness to CRH.

The Effect of Congenital and Postnatal Hypothyroidism on Depression-Like Behaviors in Juvenile Rats

“…Interestingly, in our study it was observed that the postnatal hypothyroidism group had the longest immobility time. Johnson et al (36) found that duration of hypothyroidism had different effects on the HPA axis in rats. According to their study, short-term hypothyroidism was associated with increased pituitary corticotroph responsiveness to corticotropin-releasing hormone in contrast with long-term hypothyroidism (36).…”

Glucocorticoid Functional Reserve in Full-Spectrum Intensity of Primary Hypothyroidism

“…This situation has been explained by decreased CRH mRNA expression in the hypothalamic paraventricular nucleus. At the adrenal level, in long-standing hypothyroidism, a significant reduction in cortisol secretion after ACTH has been documented in primary adrenal cell culture [15]. This finding was also supported by Tohei et al who suggest that hypothyroidism directly causes adrenal dysfunction and that hypersecretion of CRH and arginine vasopressin is due to a reduction in the negative feedback effect of glucocorticoids [23].…”

“…Once patients are clinically stable, glucocorticoids are discontinued. This therapeutic approach is based on small series of cases that have described transient adrenocortical impairment due to thyroid dysfunction and vice versa [8–15]. Most of the evidence, however, has methodological design problems that make the clinical implications of these conclusions uncertain.…”

A Novel Population of Inner Cortical Cells in the Adrenal Gland That Displays Sexually Dimorphic Expression of Thyroid Hormone Receptor-β1

“…Various correlations have been reported between thyroid hormone status and secretion of CRH, ACTH, or glucocorticoid. For example, in humans and animal models, hyperthyroidism may be associated with increased secretion (49 -52) and hypothyroidism with decreased secretion of glucocorticoid (53,54), possibly reflecting changes in adrenal function or sensitivity of the adrenal to ACTH. One explanation for these phenomena is that TR␤1 modifies the sensitivity of the adrenal cortex.…”