Thyroid hormone homeostasis in brain: possible involvement of adrenergic phenomenon in adult rat.

BACKGROUND: Imbalance in thyroid hormone concentrations has been linked with profound neurobehavioral alterations in the adult. Peripheral hypothyroidism is associated with a phenomenon of central thyroid hormone homeostasis in adult rat. This central homeostasis mechanism could be maintained by adrenergic interplay due to close physiological association between sympathetic nervous system activity and thyroid hormones. The central homeostasis is characterized by increased cerebrocortical synaptosomal T(3) content, deiodinase type II (DII) activity, and cAMP content. METHODS: We injected specific alpha- and beta-adrenergic receptor (AR) agonists and antagonists along with an anti-thyroid drug to find out any AR-mediated action on central homeostasis. RESULTS: The alpha(2)-AR agonist did not alter the onset of central homeostasis, but prolonged its duration. Similar prolongation was observed with alpha(2)-AR antagonist and beta-AR agonist, but these compounds amplified the normal anti-thyroid drug-induced rise in cerebrocortical T(3) content on the day of onset of central homeostasis. Injections of the beta-AR antagonist did not cause any perturbations. All these observations have been supported by parallel changes in cerebrocortical DII activity, cAMP and [Ca(2+)](i) content. CONCLUSION: There emerges a close correlation between cerebral T(3) content, DII activity, cAMP and [Ca(2+)](i) content that are regulated by the AR system. Thus, thyroid hormone homeostasis in the adult mammalian brain is maintained primarily by the beta-adrenergic pathway along with an unexpected pharmacological involvement of the alpha-ARs.

Maintenance of homeostasis for thyroid hormone in the adult rat brain: possible involvement of a nuclear-mediated phenomenon.

During adult-onset peripheral hypothyroidism, the brain maintains normal levels of thyroid hormone for some time through a mechanism of 'central homeostasis'. Although onset, duration, and termination of such a homeostatic phenomenon have been recently evaluated in rat models, the mechanism behind remains unknown. During our investigation to understand the mechanism further, we injected the protein synthesis blockers actinomycin D and cycloheximide along with propylthiouracil to adult male rats during the days of onset (day 2) and termination (day 20) of the homeostatic mechanism. We evaluated synaptosomal T(3) level and neuronal Na(+)-K(+)-ATPase and acetylcholinesterase activities along with deiodinase II activity and cyclic adenosine monophosphate level in the cerebral cortex. The results indicated prevalence of unchanged or lower levels of synaptosomal T(3) on the 2nd and on the 20th day, respectively. Such a condition has been parallely supported by reflections in cerebrocortical deiodinase II activity and cyclic adenosine monophosphate levels. The activities of cerebrocortical synaptosomal Na(+)-K(+)-ATPase and acetylcholinesterase, which are the two important physiological parameters for neuronal function, have been found to be supportive of the involvement of a neuronal protein-mediated factor in the 'on' and 'off' reactions in central homeostasis during peripheral hypothyroidism. The results of our study indicate that the expression of 'central thyroid hormone homeostasis' is a genomic nuclear-mediated mechanism.

Variations in hepatic estradiol-17beta receptor concentrations during the annual reproductive cycle of diploid and triploid female catfish, Heteropneustes fossilis (Bloch).

Concentrations of hepatic estradiol-17beta (E2) receptors (ER) in cytosolic and nuclear fractions were evaluated in diploid and triploid female catfish Heteropneustes fossilis (Bloch) during four different reproductive periods of a complete reproductive cycle. Basal level of ER concentration was noted in the resting period of both diploids and triploids. Receptor level gradually elevated through the preparatory period and reached a peak in the pre-spawning period in both diploids and triploids. However, ER concentrations were overall reduced in triploid to that of diploid females. In a single point assay, in diploids, ER concentration showed about a 3-fold rise (p<0.001) in the cytosolic and a 4-fold rise (p<0.001) in the nuclear extracts from resting to the pre-spawning period. In triploids, only a 2-fold rise was observed both in cytosolic (p<0.01) and nuclear (p<0.05) ER concentration during the same span. Finally, a sudden fall of receptor level was observed in the spawning period in both the ploidy groups with a lower concentration in the triploids. The K(d) value did not differ between the females of diploids (cytosolic 1.12+/-0.21 nM and nuclear 6.9+/-0.9 nM) and triploids (cytosolic--1.13+/-0.17 nM, nuclear--6.8+/-2 nM). However, B(max) of the diploid showed about double the value than triploid females both in the cytosolic (diploid--367.4+/-33.24 pmol/mg protein, triploid--187.3+/-13.20 pmol/mg protein, p<0.001) and nuclear extracts (diploid--946+/-66 pmol/mg DNA, triploid-558+/-98 pmol/mg DNA, p<0.01) of liver. Lower E2 binding capacity and lower amount of E2 receptors of triploid catfish liver with a stunted vitellogenic status could be one of the major causes for reduced gonadal development and sterility in female triploids.

Estradiol-17beta: tracing its metabolic significance in female fatbody of fifth instar larvae of silkworm, Bombyx mori L (race: Nistari).

In recent years, various vertebrate peptide and steroid hormones have been identified in invertebrates, estradiol-17beta (E2) being a major one. We have specifically shown NADP-malate dehydrogenase (NADP-MDH) activity in fifth instar larval fatbody of female silkworm, Bombyx mori, as an E2 responsive parameter. Interestingly enough, estradiol-induced increase in the enzyme activity could be counteracted by simultaneous application of specific E2-inhibitor, ICI-182780. Further, a nice correlation was obtained among the E2 titre, specific *E2 binding and expression of NADP-MDH activity in fatbody during different days of normal fifth instar larval development. Though the nature of the binding sites is quite similar to known steroid receptors of vertebrate, the reported absence of estrogen receptor gene in some insects poses a question. A recent finding regarding the presence of an estrogen-related receptor ortholog in fruit fly may provide some answers. The specific effects elicited by estradiol in the female fatbody of this insect support its possibility of having an important metabolic function. This role played by E2, whether hormonal or not, is yet to be identified.

Maintenance of brain thyroid hormone level during peripheral hypothyroid condition in adult rat.

Thyroid hormones are essential for normal functioning of adult mammalian brain. The present investigation deals with the understanding of the time course of thyroid hormone homeostasis in adult rat brain. Animals were rendered hypothyroid by PTU injections (2 mg/100 g bw) for 30 consecutive days. Serum and synaptosomal T3/T4 content, synaptosomal AChE and Na+-K+-ATPase activities were determined on alternate days. While serum T4 level initially increased on the second day compared to control, serum T3 declined in a triphasic pattern; the first phase lasting from the second day to the 6th day, the second phase ended on the 14th day and last phase continued till the 30th day. Cerebro-cortical synaptosomal T3 level increased on the 2nd day from the control, attained a peak on the 4th day, remained stable until the 18th day, and abruptly declined on the 20th day. Synaptosomal T4 content remained negligible or undetected throughout. Synaptosomal membrane Na+-K+-ATPase and AChE activity exhibited an inverse relationship during the experimental regime, being much more prominent on the 2nd, 18th and 20th day coinciding with the variations in brain T3 level. Thus, the study identifies the onset of central homeostasis between the first and second day, its continuation for about 16-18 days and its termination between the 18th and 20th day.

Thyroid hormone profile during annual reproductive cycle of diploid and triploid catfish, Heteropneustes fossilis (Bloch).

Triploid fishes generally show sterility along with retarded gonadal development and aneuploid gametes. In teleosts, thyroid hormones influence seasonal adaptations and annual events such as reproduction. In addition, thyroid hormone deposition in matured ova is important for reproductive success as the role of thyroid hormones in early development and metamorphosis is well established. The present study deals with measurements of free and total thyroxine (T4) and triiodothyronine (T3) in the plasma of triploid and diploid catfish Heteropneustes fossilis (Bloch) in a complete reproductive cycle. Accumulations of total T4 and T3 within the oocytes have also been measured during the spawning period from fishes of both ploidy groups. No difference of plasma free hormones was noticed between the diploids and triploids of both the sexes in any period of reproductive cycle, although, seasonal variations were noted in both the groups. A significant decrease in the total thyroid hormone levels was noticed in plasma of the diploids in the spawning period compared to triploid fish. During the same period, accumulation of THs was significantly higher in the oocytes of diploids than that of the triploids. Thyroid gland structure also revealed a higher state of activity in the female diploids than the triploids during spawning period. Lower activity of thyroid tissue, higher levels of THs in plasma, and lower accumulation of maternally derived hormones in the oocytes of triploid females during spawning period may be associated with sterility of triploids.

Alterations in enzyme activities in vital organs of triploid female catfish Heteropneustes fossilis (Bloch).

Triploid Heteropneustes fossilis (Bloch) showed sterility and higher growth potential than the normal diploid fish. Activities of some metabolic enzymes such as cytosolic NADP-malate dehydrogenase (NADP-MDH), mitochondrial NAD-malate dehydrogenase (NAD-MDH) and glutamate pyruvate transaminase (GPT) were evaluated in liver, brain and kidney along with glucose-6-phosphate dehydrogenase (G-6-P D) in ovary of female triploid catfish. Activities of these enzymes showed distinct seasonal periodicity, mostly with highest activities in prespawning and spawning periods, in both diploid and triploid catfish but differed in magnitude. In triploid liver, GPT showed higher activity than the diploid counterpart in prespawning and spawning periods. On the contrary, mitochondrial NAD-MDH and cytosolic NADP-MDH in this organ showed a consistent lower activity than the diploid in all stages or in some stages of reproductive cycle respectively. Interestingly, none of the enzymes in brain and kidney of triploid female catfish showed significant changes in comparison to the diploid counterpart. The triploid ovary maintained a significantly lower level of G-6-P D activity throughout the resting, preparatory and pre-spawning periods compared to the diploid ovary. Lower level of malic enzymes (NAD-MDH and NADP-MDH) in liver and G-6-P D in ovary are in close synchrony with lower level of estradiol-17beta in plasma of female triploids as found in earlier study.