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Biomedical subjects

Gerhard Schreiber

Publications and source records attributed to Gerhard Schreiber.

3 recordsLinked to original sources

Developmental profile of thyroid hormone distributor proteins in a marsupial, the tammar wallaby Macropus eugenii.

The ontogeny of thyroxine distributor proteins in serum of the marsupial Macropus eugenii (tammar wallaby) was investigated from day 3 after birth until adulthood. The thyroxine distributor proteins in the serum of adult M. eugenii are transthyretin and albumin. Northern analysis of RNA prepared from liver showed that transthyretin mRNA levels were initially high (about adult levels at the earliest ages tested), reduced to about 60% adult levels (between days 50 and 150), and then steadily increased to adult levels (by days 200 to 250). Albumin mRNA levels were initially about 50% of adult levels (day 3) and steadily rose to 90% of adult levels by days 175 to 220. A globulin, "wallaby thyroxine-binding protein" (W-TBP), bound [(125)I]thyroxine from day 3 until about day 200. Of the protein-bound thyroxine, the proportion bound by transthyretin had a similar pattern to the transthyretin mRNA levels. From day 26 onward, about half of the protein-bound thyroxine was bound to albumin. On day 3, less than 10% was bound to W-TBP and the proportion steadily increased to a maximum of about 46% by about day 120 and then reduced to undetectable levels by around day 250. The developmentally regulated W-TBP was present throughout pouch life, when the pouch young is dependent on obtaining thyroxine required for normal growth and development from the mother. After the young tammar wallaby leaves its mother's pouch, a time when it has reached a level of physiological development approximately equivalent to that at the time of birth in precocious eutherian mammals such as cattle and sheep, W-TBP was no longer detected as a thyroxine distributor protein in serum.

Aging↗

Crocodile transthyretin: structure, function, and evolution.

Structure and function were studied for Crocodylus porosus transthyretin (crocTTR), an important intermediate in TTR evolution. The cDNA for crocTTR mRNA was cloned and sequenced and the amino acid sequence of crocTTR was deduced. In contrast to mammalian TTRs, but similar to avian and lizard TTRs, the subunit of crocTTR had a long and hydrophobic NH(2)-terminal region. Different from the situation in mammals, triiodothyronine (T(3)) was bound by crocTTR with higher affinity than thyroxine (T(4)). Recombinant crocTTR and a chimeric construct, with the NH(2)-terminal region of crocTTR being replaced by that of Xenopus laevis TTR, were synthesized in the yeast Pichia pastoris. Analysis of the affinity of the chimeric TTRs showed that the NH(2)-terminal region modulates T(4) and T(3) binding characteristics of TTR. The structural differences of the NH(2)-terminal regions of reptilian and amphibian TTRs were caused by a shift in splice sites at the 5' end of exon 2. The comparison of crocodile and other vertebrate TTRs shows that TTR evolution is an example for positive Darwinian evolution and identifies its molecular mechanism.

Alligators and Crocodiles↗

The evolution of transthyretin synthesis in the choroid plexus.

Choroid plexus has the highest concentration of transthyretin (TTR) mRNA in the body, 4.4 microg TTR mRNA/g wet weight tissue, compared with 0.39 microg in the liver. The proportion of TTR to total protein synthesis in choroid plexus is 12%. All newly synthesized TTR is secreted towards the ventricles. Net transfer of T4 occurs only towards the ventricle and depends on ongoing protein synthesis. Thyroxine-binding globulin (TBG), TTR and albumin form a "buffering" system for plasma [T4] because of their overlapping affinities and on/off rates for L-thyroxine (T4)-binding. The individual components of this network determining T4 distribution are functionally highly redundant. Absence of TBG (humans), or TTR (mice), or albumin (humans, rats) is not associated with hypothyroidism. Natural selection is based on small, inheritable alterations improving function. The study of these alterations can identify function. TTR genes were cloned and sequenced for a large number of vertebrate species. Systematic, stepwise changes during evolution occurred only in the N-terminal region, which became shorter and more hydrophilic. Simultaneously, a change in function occurred: TTR affinities for T4 are higher in mammals than in reptiles and birds. L-triiodothyronine (T3) affinities show the opposite trend. This favors site-specific regulation of thyroid hormones by tissue-specific deiodinases in the brain.

Animals↗