Aging in rats is characterized by low plasma concentrations of thyroid hormones with unchanged levels of TSH, suggesting an altered TSH action in addition to the impaired regulation of TSH secretion. To evaluate TSH action we determined TSH binding to thyroid membranes of young and old male rats (3–4 and 24–26 months of age), as well as the activity of adenylate cyclase in basal and stimulated conditions. Saturation analyses of [125I]-bTSH to thyroid membranes in the presence of increasing quantities of unlabelled bTSH (0.03–100 mU) show two types of binding sites, one of high affinity (Ka 1.5 109 mol l−1) the other of lower affinity (Ka 1.2 108 mol l−1), which are similar in both age groups. The number of TSH binding sites of high affinity is less in old rats than in young rats (7.6±0.9 vs 14.8±1.1 TSH mU/mg protein, N = 11 and 10 respectively, p< <0.001), whereas the number of binding sites of low affinity is not significantly different (76.0±8.2 vs 99.1±9.0 TSH mU/mg protein). The activity of adenylate cyclase determined in basal conditions is similar in both old and young rats (1.11±0.12 vs 1.04±0.9 nmol cAMP/2 h x mg/protein). TSH (10 mU) induced a significant increase in cAMP formation with the thyroid membranes from young rats but not with those from old rats. In contrast, the stimulation of cAMP formation by GTP (2 mmol/l) or forskolin (10 mmol/l), two direct stimulators of adenylate cyclase, is similar in both groups of rats (200% and 250%, respectively). These data suggest that the reduced action of TSH on the thyroid gland of old rats is due to the decreased number of TSH binding sites, which may also be partly responsible for the low thyroid hormone secretion with aging in spite of the unchanged levels of TSH. A postreceptor defect does not seem to be involved, since direct stimulations of adenylate cyclase by GTP or forskolin are just as effective in old rats as in young rats.
Frédéric Reymond, Nicole Dénéréaz and Thérèse Lemarchand-Béraud
Alena Donda, Frédéric Reymond, François Rey and Thérèse Lemarchand-Béraud
The sex-related differences observed in the regulation of TSH secretion was further investigated by determination of the densities of T3 nuclear and TRH membrane receptors as well as the activity of 5'-deiodinase (5'D) in the anterior pituitary gland of adult male and female rats. The respective modulatory roles of androgens and estrogens on these parameters were evaluated by similar determinations carried out in castrated and in estrogen-treated male rats. The density of pituitary T3 and TRH receptors and the activity of 5'D type II were significantly greater in the female than in the male rats. The E2-treated male rats disclosed a female profile, viz. also greater densities of T3 and TRH receptors when compared with control male rats (2.3 ± 0.2 vs 1.8 ± 0.2 fmol T3/mg gland and 9.4 ± 0.8 vs 6.0 ± 0.8 fmol TRH/mg gland, mean ± sem), whereas no changes were found in the castrated rats. The E2-treated rats and the castrated rats exhibited an increased pituitary activity of 5'D, type II (0.87 ± 0.10 and 0.66 ± 0.05, respectively, vs control 0.34 ± 0.07 pmol rT3 · h−1 · (mg protein)−1), suggestive of a stimulatory effect of E2 and of an inhibitory effect of androgens on this parameter. In contrast, no differences in hepatic 5'D were found between all groups, illustrating the well-known tissue-specific regulation of 5'D. These results demonstrate that the sex difference in the density of pituitary T3 and TRH receptors and the activity of 5'D in the adult rat is mainly due to a modulatory effect of estrogens, which may be responsible for the sex-dependent regulation of TSH secretion.