Biomedical subjects

Heike Heuer

Publications and source records attributed to Heike Heuer.

4 recordsLinked to original sources

PubMed2003

Thyroid hormone induces cerebellar Purkinje cell dendritic development via the thyroid hormone receptor alpha1.

The thyroid hormone l-3,3',5-triiodothyronine (T3) plays an important role during cerebellar development. Perinatal T3 deficiency leads to severe cellular perturbations, among them a striking reduction in the growth and branching of Purkinje cell dendritic arborization. The molecular mechanisms underlying these effects are poorly understood. Despite the well documented broad expression of thyroid hormone receptors (TRs), analysis of different TR-deficient mice has failed to provide detailed information about the function of distinct TRs during neuronal development. The cerebellar cell culture systems offer an excellent model by which to study the effects of T3, because differentiation of cerebellar neurons in mixed and purified cultures proceeds in the absence of serum that contains T3. Addition of T3 to cerebellar cultures causes a dramatic increase in Purkinje cell dendrite branching and caliber in a dose- and time-dependent manner. Furthermore, we demonstrate for the first time that T3 acts on Purkinje cells directly through TRalpha1 expressed on the Purkinje cell and not on the granule cell, the presynaptic partner of Purkinje cells. In contrast, TRbeta isoforms are not involved, because Purkinje cells derived from TRbeta-/- mice show the same T3 responsiveness as wild-type cells. T3-promoted Purkinje cell differentiation was not mediated via neurotrophins, as suggested previously, because dendritogenesis of Purkinje cells from BDNF-/- mice could be effectively stimulated in vitro by T3 treatment. Furthermore, the effects of T3 observed were not abolished by tyrosine kinase receptor B (TrkB)-IgG, TrkC-IgG, or K252a, agents known to block the actions of neurotrophin. These results indicate that T3 directly affects Purkinje cell differentiation through activation of the TRalpha1.

Animals↗

PubMed2003

Expression of pituitary hormones in the Pax8-/- mouse model of congenital hypothyroidism.

Signaling mechanisms in pituitary morphogenesis as well as pituitary cell fate determination during early embryonic development are relatively well characterized. In contrast, the cues that determine the progression of the various anterior pituitary cell types during postnatal periods are poorly defined. Pax8-/- mice, which are born without a thyroid gland, were used to study the influence of thyroid hormones on the expression of pituitary hormones during early postnatal life. Serum pituitary hormones were determined by RIAs, and the pituitaries were analyzed by Northern blotting, in situ hybridization histochemistry, and immunocytochemistry. In 21-d-old Pax8-/- mice, the cellular composition of the anterior pituitary was dramatically distorted. Thyrotropes exhibited hypertrophy and hyperplasia, the number of detectable somatotropes was drastically reduced, and lactotropes were almost undetectable. Expression of LH and FSH was also reduced, but ACTH and proopiomelanocortin expression was not significantly different. Serum pituitary hormone levels were changed correspondingly. T(4) replacement therapy for variable time periods normalized TSH and GH mRNA expression within 3 d but not prolactin expression, not even when T(4) was administered for 6 d in combination with estradiol. These findings reveal the importance of thyroid hormones in developing the appropriate proportions of anterior pituitary cell types, especially with regard to lactotropes.

Age Factors↗

PubMed2003

CTGF expression during mouse embryonic development.

Connective tissue growth factor (CTGF) is a potent fibroblast mitogen and angiogenic factor which plays an important role in wound healing, cancerogenesis and fibrotic and vascular disease. Here we explored the regulation and the cellular site of the mRNA synthesis for this growth factor in the developing mouse embryo by in situ hybridisation. Strong and persistent CTGF gene expression was limited to three types of tissue: the vascular endothelium, particularly the high-pressure part of the cardiovascular system, condensed connective tissue around bone and cartilage, and maturing layer VII neurons in the cerebral cortex. With few exceptions (late tooth bud, neuroepithelium) epithelial tissue was negative. Very transient but strong expression was observed early during formation of cartilage, in late stages during perichondral ossification, on cerebral neuroepithelium, and in several discrete stages of tooth formation, on mesenchymal precursors of odontoblasts condensing on inner dental epithelium, and later on apposing regions of ameloblast and odontoblast epithelium. Altogether, the current study suggests that CTGF performs a dual role: a continuous function in the cardiovascular system, bone and cartilage-associated mesenchyme and maturing layer VII neurons, but also a more transient function associated with the formation of cartilage, bone, tooth and cerebral nerve cells.

Animals↗

PubMed2003

Regulation of iodothyronine deiodinases in the Pax8-/- mouse model of congenital hypothyroidism.

Thyroid hormones are essential for a variety of developmental and metabolic processes. Congenital hypothyroidism (CHT) results in severe defects in the development of different tissues, in particular brain. As an animal model for CHT, we studied Pax8(-/-) mice, which are born without a thyroid gland. We determined the expression of iodothyronine deiodinase D1 in liver and kidney, D2 in brain and pituitary, and D3 in brain, as well as serum T(4), T(3), and rT(3) levels in Pax8(-/-) vs. control mice during the first 3 wk of life. In control mice, serum T(4) and T(3) were undetectable on the day of birth (d 0) and increased to maximum levels on d 15. In Pax8(-/-) mice, serum T(4) and T(3) remained below detection limits. Serum rT(3) was high on d 0 in both groups and rapidly decreased in Pax8(-/-), but not in control mice. Hepatic and renal D1 activities and mRNA levels were low on d 0 and increased in control mice roughly parallel to serum T(4) and T(3) levels. In Pax8(-/-) mice, tissue D1 activities and mRNA levels remained low. Cerebral D2 activities were low on d 0 and increased to maximum levels on d 15, which were approximately 10-fold higher in Pax8(-/-) than in control mice. D2 mRNA levels were higher in Pax8(-/-) than in control mice only on d 21. Cerebral D3 activities and mRNA levels were high on d 0 and showed a moderate decrease between d 3 and 15, with values slightly lower in Pax8(-/-) than in control mice. One day after the injection of 200 ng T(4) or 20 ng T(3)/g body weight, tissue deiodinase activities and mRNA levels were at least partially restored toward control levels, with the exception of cerebral D3 activity. In conclusion, these findings show dramatic age and thyroid state-dependent changes in the expression of deiodinases in central and peripheral tissues of mice during the first 3 wk of life.

Aging↗