corticosterone-acetate and Hypothyroidism

The low affinity glucocorticoid binding sites (LAGS) have been described and partially characterized in both the nuclei and microsomes of rat liver. The LAGS concentration is under endocrine regulation, as proved by their decrease after adrenalectomy and their almost complete disappearance after hypophysectomy. This article describes new data that also implicate the thyroid hormones in the endocrine regulation of LAGS. The LAGS were measured by [3H]dexamethasone exchange assay in crude microsome suspensions of rat liver. Propylthiouracil-induced hypothyroidism (TX) provoked a 90% reduction in the LAGS levels with respect to the control value. The administration of T3 to TX rats was able to completely restore the LAGS level. On the other hand, adrenalectomy (ADX) provoked a 50% decrease in LAGS levels, and this effect could be reverted by treatment with corticosterone acetate. TX rats that were also adrenalectomized (TX-ADX) showed a LAGS level similar to that of the TX rats. However, treatment of these rats with T3 was much less effective than in TX rats. A complete restoration of the LAGS level in TX-ADX rats could be achieved only with a combined treatment of corticosterone acetate plus T3. Similar results to those obtained in TX-ADX rats were also obtained in immature or hypophysectomized rats, two experimental models known to possess very low or undetectable levels of LAGS. From these findings we conclude that: 1) thyroid hormones, as well as glucocorticoids, play an important role in the regulation of the LAGS level; 2) glucocorticoids and thyroid hormones act synergistically in the endocrine regulation of LAGS; and 3) the results obtained in the hypophysectomized rats point to a direct action of glucocorticoids and T3 on the LAGS level of the rat liver.

Topics: Adrenalectomy; Animals; Binding Sites; Corticosterone; Dexamethasone; Drug Synergism; Glucocorticoids; Hypophysectomy; Hypothyroidism; Male; Microsomes, Liver; Propylthiouracil; Rats; Rats, Inbred Strains; Receptors, Glucocorticoid; Thyroid Hormones; Triiodothyronine

Two types of iodothyronine 5'-deiodination have been characterized previously in rat tissues. They can be distinguished by inhibition of type I but not type II by 6-n-propylthiouracil, by the relative suitability of T4 and rT3 as substrates, rT3 much better than T4 for type I and T4 as good as, or better than, rT3 for type II, and by the concentration of T4 required to inhibit deiodination of rT3, 1-10 microM for type I and 1-10 nM for type II. Type I activity (6-n-propylthiouracil sensitive) is most abundant in liver and kidney. Type II activity has, to date, been identified only in the pituitary, central nervous system, and brown adipose tissue. Iodothyronine tyrosyl deiodination has also been identified in homogenates of rat brain, liver, and placenta. It is not clear how many different enzymes carry out this latter reaction. In the present studies, we have extended previous work by determining maturational patterns of the deiodinating pathways in several thyroid hormone-responsive rat tissues, possible modulation of those patterns by glucocorticoids, and the age of onset of responsivity of the deiodinases to hypothyroidism. Iodothyronine 5'-deiodinating activity was found in rat lung and eye, and the reaction was all or nearly all type I in both. Activity in the eye was virtually absent from the lens and vitreous humor. In immature rat cerebrum, pituitary, lung, and eye, between gestational day 17 and postnatal day 21, there was a uniform pattern of an increase in type I 5'-deiodination activity over time, until adult levels were attained. The ages at which adult activity levels were reached varied from tissue to tissue, however. Type II activity was present at the earliest ages tested in the cerebrum (gestational day 17), pituitary, and brown adipose tissue (day of birth). In cerebral cortex, type II activity was highest at day 21 postnatally and equal at birth and in adulthood, and in pituitary and brown adipose tissue it was higher in adulthood than at birth. T3 tyrosyl ring deiodinating activity was several times greater in homogenates of eye and placenta than in cerebral homogenates. In all three tissues, there was similar, dose-dependent inhibition of [125I]T3 tyrosyl deiodination by 5 nM and 20 nM nonradioactive T3. In the eye and brain, T3 tyrosyl deiodination rates decreased progressively with age from gestational day 17 to postnatal day 7.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Adipose Tissue, Brown; Age Factors; Animals; Brain; Corticosterone; Eye; Female; Hypothyroidism; Lung; Male; Pituitary Gland; Pregnancy; Rats; Rats, Inbred Strains; Thyronines; Triiodothyronine, Reverse