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Background  Age-dependent alterations of hormonal states have been considered to be involved in age related decline of cognitive abilities. Most of the studies in animal models are based on hormonal substitution in adrenal- and/or gonadectomized rodents or infusion of steroid hormones in intact rats. Moreover, the manipulations have been done timely, closely related to test procedures, thus reflecting short-term hormonal mechanisms in the regulation of learning and memory. Here we studied whether more general states of steroid and thyroid hormone profiles, independent from acute experiences, may possibly reflect long-term learning capacity. A large cohort of aged (17–18 months) intact male rats were tested in a spatial hole-board learning task and a subset of inferior and superior learners was included into the analysis. Young male adult rats (16 weeks of age) were also tested. Four to 8 weeks after testing blood plasma samples were taken and hormone concentrations of a variety of steroid hormones were measured by gas chromatography-tandem mass spectrometry or radioimmunoassay (17β-estradiol, thyroid hormones).    Results  Aged good learners were similar to young rats in the behavioral task. Aged poor learners but not good learners showed higher levels of triiodothyronine (T3) as compared to young rats. Aged good learners had higher levels of thyroid stimulating hormone (TSH) than aged poor learning and young rats. Both aged good and poor learners showed significantly reduced levels of testosterone (T), 4-androstenedione (4A), androstanediol-3α,17β (AD), dihydrotestosterone (DHT), 17-hydroxyprogesterone (17OHP), higher levels of progesterone (Prog) and similar levels of 17β-estradiol (E2) as compared to young rats. The learning, but not the memory indices of all rats were significantly and positively correlated with levels of dihydrotestosterone, androstanediol-3α,17β and thyroxine (T4), when the impacts of age and cognitive division were eliminated by partial correlation analyses.    Conclusion  The correlation of hormone concentrations of individuals with individual behavior revealed a possible specific role of these androgen and thyroid hormones in a state of general preparedness to learn.

Age and cognitive status dependent differences in blood steroid and thyroid hormone concentrations in intact male rats