Oestrogens in the mammalian brain: from conception to adulthood--a review.

Environmental and plant oestrogens have been identified as compounds that when ingested, disrupt the physiological pathways of endogenous oestrogen actions and thus, act as agonists or antagonists of oestrogen. Although the risks of exposure to exogenous oestrogens (ExEs) are subject to scientific debate, the question of how ExE exposure affects the central nervous system remains to be answered. We attempt to summarise the mechanisms of oestrogenic effects in the central nervous tissue with the purpose to highlight the avenues potentially used by ExEs. The genomic and rapid, non-genomic cellular pathways activated by oestrogen are listed and discussed together with the best known interneuronal mechanisms of oestrogenic effects. Because the effects of oestrogen on the brain seem to be age dependent, we also found it necessary to put the age-dependent oestrogenic effects in parallel to their intra- and intercellular mechanisms of action. Finally, considering the practical risks of human ExE exposure, we briefly discuss the human significance of this matter. We believe this short review of the topic became necessary because recent data suggest new fields and pathways for endogenous oestrogen actions and have generated the concern that the hidden exposure of humans and domestic animal species to ExEs may also exert its beneficial and/or adverse effects through these avenues.

Cloning and characterization of the bovine MHC class I-like Fc receptor.

In the cow, maternal immunity is exclusively mediated by colostral Igs, but the receptor responsible for the IgG transport has not yet been identified. The role of an IgG-Fc receptor (FcRn) that resembles a class I MHC Ag in transporting IgGs through epithelial cells was recently shown in selected species. We now report the cloning and characterization of the bovine FcRn (bFcRn). The cDNA and deduced amino acid sequences show high similarity to the FcRn in other species, and it consists of three extracellular domains, a hydrophobic transmembrane region, and a cytoplasmic tail. Despite the high similarity of the extracellular domains with other species, the bovine cytoplasmic tail is the shortest thus far analyzed. Aligning the known FcRn sequences, we noted that the bovine protein shows a 3-aa deletion compared to the rat and mouse sequences in the alpha1 loop. Furthermore, we found a shorter transcript of the bFcRn reflecting an exon 6-deleted mRNA, which results from an inadequate splice acceptor site in intron 5 and produces a transmembrane-deficient molecule, as was previously demonstrated in the related MHC class I gene family in mouse and humans. The presence of bFcRn transcripts in multiple tissues, including the mammary gland, suggests their involvement both in IgG catabolism and transcytosis.

Expression of the murine wild-type tyrosinase gene in transgenic rabbits.

The tyrosinase gene is known to be essential for melanization and has been shown to rescue pigmentation in albino mice. Previously we have described the strict copy-number-dependent expression of a murine wild-type tyrosinase gene construct over several generations in transgenic mice. In this study, we analysed the same gene construct as a marker gene for the transmission and expression of transgenes in rabbits. Using an albino hybrid strain, we produced transgenic rabbits expressing the murine tyrosinase gene. Strict correlation between integration and expression of the transgene and stable germline transmission of the integrated gene construct according to the Mendelian pattern of inheritance was observed. Thus, breeding control was facilitated by simple phenotypic examination of the transgenic animals. In contrast to mice transgenic for the same gene construct, tyrosinase-transgenic rabbits showed a greater variety in hue, intensity and extent of coat pigmentation, which is caused by the diversity in the loci affecting the melanization. Benefits and limitations of tyrosinase as a marker gene for the detection of homozygous individuals in the albino hybrid strain used are discussed.

T-cell subsets in blood and lymphoid tissues obtained from fetal calves, maturing calves, and adult bovine.

Assessment of CD2, CD4, CD8 and gamma delta cell distribution among mononuclear cells obtained from the blood and lymphoid tissues of fetal calves, 0-150-day-old calves and adult cows was the focus of this investigation. The distributions of some of the lymphocyte subsets in peripheral blood showed variation in fetal and maturing calves as well as being markedly different from those observed in adult cows. We provide evidence that as early as 1 month prepartum, fetal calves have a full complement of at least four of the major T-cell subsets found in the normal bovine. In blood, CD2(+) were significantly higher at 1, 30 and 90 days of age, CD4(+) and CD8 cells demonstrated a peak in the fetuses that dropped below adult levels from 1 to 120 days of age, and gamma delta (+) cells were highest at birth and decreased to adult levels by 150 days of age. Except for the gamma delta (+) cells, the subsets were significantly higher in lymphoid tissues obtained from fetal and maturing calves than in the mature animals. All four subsets were significantly higher in fetal and young calf splenic tissues. No significant differences were observed in the distribution of the four subsets in thymuses assayed in this study. An interesting pattern was seen in a longitudinal study of T-cell subsets that showed 7-8 day cyclical changes in CD2 and CD4 marked cells in adult peripheral blood.

Thyroid hormone deiodination in the brain of young chickens acutely adapts to changes in thyroid status.

The brain represents a special organ in respect of thyroid hormone handling. This was analyzed in one-week-old chickens. The effect of sham-operation (SH), thyroidectomy (TX) and thyroidectomy plus thyroxine supplementation (TX+T4) on the intracerebral triiodothyronine (T3) content and on the activity of different types of deiodinases was investigated. it was found that in spite of very low T3 levels in the serum of TX animals, the brain displayed close to normal tissue T3 levels. Kinetic studies of the deiodinase system showed an increase in type II activity (increased T4 to T3 conversion) and decreased type III activity (decreased degradation of intracellular T3) in the brain of TX animals vs. SH or TX+T4. It is concluded that a considerable part, if not the total of the T3 preserved in hypothyroidism may be ascribed to adaptive changes of the deiodinase system in the brain of young chickens.

The isotypic, allotypic and idiotypic heterogeneity of bovine IgG2.

The antigenic heterogeneity of bovine IgG2 observed by single radial diffusion, when different cattle sera are tested with a panel of IgG2-specific reagents, was examined by a combination of biochemical and serological assays. Using an autologous anti-A1 allotypic reagent, the major antigenic heterogeneity detected by swine, rabbit and goat anti-IgG2 reagents was due to their propensity to recognize the AI allotope. All heterologous reagents and most monoclonals so far test are biased in their specificity toward this determinant. A second type of serological heterogeneity, recognized by only certain heterologous reagents, was their specificity for what we have called the IgG2b isotype of IgG2. This isotype is found in all cattle, has a restricted ion-exchange elution behaviour and does not bear a-locus allotypic determinants; molecules bearing the latter are now designated IgG2a. IgG2a elutes from anion-exchange columns in subpopulations over a wide range of ionic strength including fractions which contain IgG2b and IgG1 as well. Using IgG2a from an AI homozygous steer, these subpopulations were shown to result from idiotypic variation which appears to primarily reside in their VH-regions.

The heterogeneity of bovine IgG2. II. The identification of IgG2b.

Goat and rabbit polyclonal reagents can be raised which recognize a new isotype of bovine antibodies. The polyclonal goat reagent was raised against a preparation enriched in the major IgG2 isotype (IgG2a) which contained the new isotype as a contaminant. The polyclonal rabbit reagent was prepared against a trypsin-derived Fc fraction of bovine IgG1 which contained the Fc of the new isotype as a contaminant. This new isotype is present in the sera of the cattle of all breeds tested regardless of their IgG2a allotype and is antigenically distinct from IgG2a, IgG1, IgA, IgM and IgE. The new isotype coelutes from DEAE anion exchangers with IgG1 and the more acidic populations of IgG2a. The isotype is tentatively designated IgG2b. The distribution of IgG2b antibody activity to E. coli K99 and phosphorylcholine among 15 cattle of different A allotypes is not correlated with the IgG2a or IgG1 antibody activity in these animals.