Endocrine and metabolic function in male Carioca High-conditioned Freezing rats.

The aim of this study was to characterize Carioca High-conditioned Freezing rats (CHF) regarding their endocrine and metabolic backgrounds. We found an increase in serum corticosterone (CTRL: 96.7 ± 21.65 vs CHF: 292.0 ± 4 0.71 ng/ml) and leptin (CTRL: 9.5 ± 1.51 vs CHF: 19.2 ± 4.32 ng/ml). Serum testosterone (CTRL: 3.3 ± 0.29 vs CHF: 2.0 ± 0.28 ng/ml) and T3 (CTRL: 52.4 ± 2.74 vs CHF: 42.7 ± 2.94 ng/dl) were decreased in the CHF group, but serum TSH and T4 were unaffected. Body weight and food intake were unchanged, nevertheless retroperitoneal fat (CTRL: 2.2 ± 0.24 vs CHF: 4.8 ± 0.64 g) and epididymal fat (CTRL: 2.6 ± 0.20 vs CHF: 4.8 ± 0.37 g) depot weights were around 2-fold higher in CHF animals. BAT weight was similar in both groups. Serum triglycerides (CTRL: 41.4 ± 6.03 vs CHF: 83.2 ± 17.09 mg/dl) and total cholesterol (CTRL: 181.6 ± 5.61 vs CHF: 226.4 ± 13.04 mg/dl) were higher in the CHF group. Fasting glycemia (CTRL: 68.7 ± 3.04 vs CHF: 82.3 ± 2.99 mg/dl) was also higher in the CHF group, however glucose tolerance test response and serum insulin levels were similar between the groups. Oxygen consumption (CTRL: 10.5 ± 0.40 vs CHF: 7.9 ± 0.58 VO2ml/min/kg(0.75)) and BAT D2 activity (CTRL: 0.7 ± 0.17 vs CHF: 0.3 ± 0.04 fmolT4/min/mg ptn) were lower in the CHF group. Our data show that anxiety could impair endocrine and metabolic functions and may contribute to the development of metabolic diseases.

Effects of ageing and pharmacological hypothyroidism on pituitary-thyroid axis of Dutch-Miranda and Wistar rats.

To evaluate the ability of the aged rat pituitary to increase TSH secretion in response to major decreases in serum thyroid hormones, hypothyroidism was induced by methimazole in young and old, male and female, Dutch-Miranda and Wistar rats. Before MMI-treatment there were no differences in serum TSH of young and old rats, but serum T(4) was significantly decreased in aged rats from both genders and strains, while serum T(3) was significantly decreased in aged male rats from both strains, and in old Wistar females. MMI treatment significantly decreased serum T(4) and T(3) in all treated animals, and progressively increased serum TSH in both male and female rats, but the increase was significantly smaller in the elder rats. The pituitary TSH content was higher in Wistar than in Dutch-Miranda rats, of both genders, and was not significantly affected by age. MMI treatment decreased the pituitary TSH in both young and old Dutch-Miranda rats, but in the Wistar strain only the old females had a significant decrease. Our results show that the ability of the pituitary thyrotrophs to increase hormonal secretion in response to decreased levels of thyroid hormones is impaired in the old rat, even when the thyroid hormone levels are dramatically reduced.

Bradykinin B1 receptor stimulates the proximal tubule Na(+)-ATPase activity through protein kinase C pathway.

Recently, our group described a B1-mediated stimulatory effect of des-Arg(9)-bradykinin (DABK) on the Na(+)-ATPase activity of proximal tubule basolateral membranes (BLM) [Biochim. Biophys. Acta 1431 (1999) 483.]. Data in the present report suggest the participation of a phosphatidylinositol-specific PLC (PI-PLC)/protein kinase C (PKC) pathway as the molecular mechanism of DABK-mediated stimulation of the Na(+)-ATPase activity since (i) 10(-8) M DABK activates PI-PLC activity; (ii) 10(-9) M U73122, a PI-PLC inhibitor, abolishes the effect of 10(-8) M DABK on the Na(+)-ATPase activity; (iii) 10(-8) M DABK increases phosphoprotein formation by 34%. This effect is completely reversed by 10(-7) M calphostin C, an inhibitor of PKC; (iv) 20 ng/ml TPA, an activator of PKC, and 10(-8) M DABK stimulate the Na(+)-ATPase activity in a similar and nonadditive manner. Furthermore, the effect of 10(-8) M DABK is completely reversed by calphostin C; (v) 10(-8) M DABK increases phosphoserine residue levels by 54%. This effect is completely reversed by 10(-7) M calphostin C.

Thyroid and pituitary thyroxine-5'-deiodinase activity and thyrotrophin secretion in lithium-treated rats.

Some authors have reported increased serum thyrotrophin (TSH) in animals chronically treated with lithium, suggesting that lithium might decrease pituitary thyroxine (T(4))-5'-deiodinase activity. On the other hand, the effect of lithium treatment on thyroidal T(4)-5'-deiodinase activity is also unknown. The present study was undertaken to evaluate the effects of lithium treatment on pituitary and thyroid T(4)-5'-deiodinase activity. Serum and pituitary TSH levels and thyroidal and pituitary T(4)-5'-deiodinase activities were determined in 3-month-old isogenic male Dutch-Miranda rats treated with lithium for 8 weeks. Chronic lithium treatment produced a slight increase in pituitary TSH content, but no change in serum TSH, and a significant increase in the thyroidal T(4)-5'-deiodinase activity. However, the pituitary T(4)-5'-deiodinase activity was unaffected by lithium administration. As far as we know, the present data show for the first time that chronic lithium treatment can increase the thyroxine to tri-iodothyronine conversion in the murine thyroid gland, be it directly or indirectly.

Effect of aging on thyroidal and pituitary T4-5'-deiodinase activity in female rats.

Some alterations in hypothalamo-pituitary-thyroid axis occur during aging. In this study we evaluated the changes induced by aging in pituitary and thyroid iodothyronine-deiodinase (DI) activities, and in serum T4, T3 and TSH. Groups of 6-18 female Dutch-Miranda rats aged 3-5 months (young adults) were studied in parallel with similar groups of old (10-12 months) and senescent (24-30 months) animals. DI activities were determined in the microsomal fraction of pooled pituitary or thyroid glands (6 glands per pool), using T4 as substrate and DTT as cofactor; the T3 formed was measured by specific radioimmunoassay. Serum T3, T4 and TSH were measured by specific radioimmunoassays. Serum T4 was significantly decreased in both groups of aged rats, but serum TSH was unaffected. Serum T3 was just slightly decreased in the senescent rats. Total pituitary DI activity was significantly decreased in the aged rats (10-12 and 24-30 months). Both type I and type II DI activities were affected, although the decrease in type I DI only became significant in the senescent rats. In contrast, to its effect in the pituitary, aging does not decrease, even slightly, the DI activity in the thyroid gland. The thyroid DI activity may contribute to the unaltered serum T3 levels found in aged rats in the present study.