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Biomedical subjects

Stephanie Christ

Publications and source records attributed to Stephanie Christ.

6 recordsLinked to original sources
PubMed2005

Gene expression of connective tissue growth factor in adult mouse.

The connective tissue growth factor (CTGF) is a well-known fibroblast mitogen and angiogenic factor that plays an important role in bone formation during embryogenesis. In the adult, CTGF is involved in wound healing as well as fibrotic and vascular disease. However, little is known about its physiological functions under non-pathological conditions in the adult organism. Here, we describe the cellular site of the CTGF mRNA expression in adult male and female mice as revealed by in situ hybridization histochemistry. Strong and persistent CTGF gene expression was particularly prominent in the mesenchyme of the cardiovascular system (aorta, auricular tissue, renal glomeruli), the mesenchyme surrounding the ovarian follicles or the testicular tubes in the gonadal tissue, and the subcapsular mesenchyme bordering densely innervated parts of whisker hair vibrissae. CTGF hybridization signals were not observed in the mesenchyme of many other organs including gut, muscle, liver or most parts of the lymphatic tissue. Strong expression was also present in the primary (early) ovarian follicles, the epithelium of the deep uterine glands and on myenteric ganglia neurons. These data suggest a selective and continuous mesenchymal function in the gonads and those tissues attracting very strong vascular supply or peripheral innervation. CTGF may also be involved in the cyclical proliferation of the uterine gland epithelium and in the early stages of follicular maturation, as well as in the neuropeptide regulation in the gut, cardiovascular and renal systems.

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↗
PubMedDate not supplied

Hearing loss in athyroid pax8 knockout mice and effects of thyroxine substitution.

Pax8-/- mice do not develop thyroid follicular structures and thus provide an ideal animal model to study the consequences of congenital hypothyroidism. Despite their athyroidism, Pax8-/- mice survive up to postnatal day 21 (P21). No auditory brain stem responses (ABR) to sound could be recorded in these animals at 130 dB SPL, even at P21, when hearing reaches adult sensitivity in control mice. Abnormalities in the outer and middle ear structures were found in a considerable percentage of Pax8-/- animals. Maturation of the inner ear appeared delayed by about 1 week with respect to euthyroid controls. Hearing of adult Pax8-/- mice could be nearly normalized by early postnatal substitution with thyroxine (T(4)), but structural and functional restoration of hearing was incomplete. Even when T(4) substitution was initiated at P1, ABR thresholds, measured at 6 weeks of age or more, were increased by about 20 dB, and each day of delay in the start of T(4) substitution resulted in an additional threshold loss of about 4 dB. The most prominent structural deficit in Pax8-/- animals in which T(4) substitution was started at P8 or later was an abnormally thick tectorial membrane. In these late-substituted animals, disarray of stereovilli from inner and outer hair cells was observed and also outer hair cell loss was found, predominantly in the basal part of the cochlea. The degree of structural disorder increased the later T(4) substitution was initiated. The structural and functional consequences of postnatal athyroidism observed in Pax8-/- mice are largely in agreement with and extend those data obtained from hypothyroid animal models in which hypothyroidism was induced by goitrogenic agents (methimazole, propylthiouracil) or animal models with disrupted genes for the TSH receptor or the thyroid hormone receptors. The hearing loss and also the recovery effect by T(4) substitution in Pax8-/- mice is larger than that in the other models. Although Pax8-/- mice are born by euthyroid Pax8+/- dams, the Pax8-/- phenotype could not be completely restored by immediate postnatal T(4) substitution, indicating that some deficits are the consequence of prenatal T(4) deficiency of the offspring.

Animals↗