The Thyroid Hormone, 3,5,3′-Triiodothyronine, Is a Negative Modulator of Domestic Fowl (Gallus gallus domesticus) Adrenal Steroidogenic Function

Previous work with chickens (Gallus gallus domesticus) suggests a relationship between depressed thyroid hormone status and enhanced adrenal steroidogenic function. In addition, in hypophysectomized chickens, replacement of the thyroid hormone, 3,5,3′-triiodothyronine (T3), maintains chicken adrenal steroidogenic cell sensitivity to adrenocorticotropin (ACTH) but decreases steroidogenic capacity further than that due to hypophysectomy alone. The presentin vivoandin vitrostudies were conducted to determine the influence of thyroid status and T3per se on avian adrenal steroidogenic function. Chicks (1 day old) were thyroidectomized using combined surgical and chemical (6-propyl-2-thiouracil) treatments and were administered a replacement dose of T3(0, 1.5, 4.5, 15, and 45 μg/kg body wt/day) for 5 weeks. Whereas thyroidectomy (TX) decreased adrenal weight (−20%), it increased relative adrenal weight (mg/100 g body weight) (+171%), trunk plasma corticosterone (+880%), and aldosterone (+124%). In addition, TX increased basal, maximal ACTH-induced, maximal 8-bromo-cyclic AMP-induced, and maximal 25-hydroxycholesterol-supported corticosterone production (+520, +93, +124, and +195%, respectively) and aldosterone production (+578, +288, +280, and +275%, respectively) by isolated adrenal steroidogenic cells. T3, in a dose-dependent manner, reversed the effects of TX on thesein vivoandin vitroparameters of adrenal steroidogenic function. Restoration of most of these parameters to those in the sham-treated control was attained with 4.5–15 μg/kg body wt/day. Although some of the effects of TX and T3replacement on adrenal steroidogenic function may have been mediated through changes in circulating levels of ACTH, other data suggest a direct effect on adrenal steroidogenic cell function. Adrenal steroidogenic cells from sham-treated and TX birds were preincubated (0, 4, and 12 hr) with various concentrations of T3(0, 0.3, 3, and 30 nM), washed, and then incubated for an additional 2 hr in medium containing the same respective concentrations of T3, with or without a maximal steroidogenic concentration of ACTH (100 nM). T3had no acute effects on TX-dependent enhancement of adrenal steroidogenic cell function (2-hr incubation). However, with preincubation (4 and 12 hr), T3inhibited basal and maximal ACTH-induced corticosterone production in a dose-dependent manner. This concentration-dependent, direct effect of T3was not observed with cells from sham-treated birds. In addit