Registration Dossier

Administrative data

Endpoint:
biochemical or cellular interactions
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Non-GLP, non-guideline study

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1992

Materials and methods

Test guideline
Qualifier:
no guideline available
GLP compliance:
no
Type of method:
in vivo
Endpoint addressed:
not applicable

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
not specified

Examinations

Examinations:
Isoelectric focusing (IEF) of serum samples incubated with 125-I-labelled T4

Results and discussion

Any other information on results incl. tables

IEF study of TBG microheterogeneity during ontogenesis

Serum from rats of different ages, from 19-day embryos to 60-day post-natal animals, was incubated with radioiodinated T4 and then submitted to IEF in the pH range 4-5 (Fig. 1). The age-related labelling density pattern of the TBG zone on the autoradiogram was consistent with the developmental trend of the protein, as demonstrated in previous binding, immunological and biosynthetic studies: absence in the foetus, appearance and increasing concentration in neonates, then decline and finally disappearance in young adults. The weak labelling of transthyretin (TTR) in the growing pups reflects the

successful competition of the co-existing TBG for the common T4 ligand.

The polymorphism of TBG, first observed in serum from 8-day-old rats, is maintained throughout development, with respect to both number and isoelectric points (pl) of isoforms.

The protein is separated into six bands with pl values between 4.25 and 4.55. The distribution of the T4 ligand among TBG isoforms is uneven at all ages. Moreover, this pattern of unequal labelling markedly changes during ontogenesis: in the neonates, the greatest labelling is seen with the most alkaline bands, but with increasing age of the animals it shifts gradually tot the most acidic bands.

Applicant's summary and conclusion

Conclusions:
Thyroxine-binding globulin (TBG), the major carrier of thyroid hormones in human and murine sera, is in the rat a developmentally regulated protein, showing a large surge during post-natal growth followed by virtual disappearance in adults.