Search Results

You are looking at 1 - 3 of 3 items for

  • Author: CJ McCabe x
  • Refine by Access: All content x
Clear All Modify Search
Free access

CJ McCabe and NJ Gittoes

The pathogenesis of sporadic pituitary tumours remains elusive. Recently, a new candidate gene has been described which is able to induce pituitary cell transformation, and the expression of which appears to be strongly correlated with pituitary tumorigenesis. The so-called pituitary tumour transforming gene (PTTG) encodes a 23 kDa, 202 amino acid protein, and is located on chromosome 5q33, a locus previously associated with recurrent lung cancer and acute myelogenous leukaemias. Although the precise function of PTTG protein is unknown, in vitro experiments have demonstrated that it is capable of inducing fibroblast growth factor (FGF) expression. Mutation of the two proline-rich domains of the PTTG protein has also been shown to abolish subsequent FGF induction. Furthermore, in patients with pituitary adenomas, serum FGF concentrations fall post-operatively after successful excision of the tumour.

Free access

CM Bishop, CJ McCabe, NJ Gittoes, PJ Butler, and JA Franklyn

Skeletal muscles are important target tissues for thyroid hormone action. The present study examines the influence of thyroid status on muscle growth and tissue-specific expression of thyroid receptor (TR) mRNA isoforms in a commercial strain of the domestic duck (Anas platyrhynchos). Four groups (n=5) of 1-week-old ducklings were rendered either hypothyroid by treatment with methimazole (6 mg 100 g(-1) body mass or 12 mg 100 g(-1) body mass), or hyperthyroid by treatment with methimazole (6 mg 100 g(-1) body mass) in combination with thyroid hormones (5 microg thyroxine (T(4)) and tri-iodothyronine (T(3)) 100 g(-1) body mass or 10 microg T(4) and T(3) 100 g(-1) body mass). Serum and tissue samples (cardiac, pectoralis and semimembranosus leg muscle, liver, pituitary and cerebral cortex) were collected from these four groups, and from a group of untreated controls, at 8 weeks of age. Development of duckling morphology was retarded in methimazole-treated birds compared with that in euthyroid controls, as evidenced by differences in skeletal dimensions, primary feather length, and body and muscle masses. Body mass was lower by 18%, and relative masses of cardiac and pectoralis muscles were lower by 28% and 32% respectively. Heterologous oligonucleotides for TR alpha, TR beta 0, TR beta2 and the housekeeping gene beta-actin were derived from chicken sequences. RT-PCR showed that TR alpha mRNA was expressed in all tissues but was not significantly affected by any of the experimental treatments. TR beta 0 mRNA expression was significantly lower in the leg muscles of ducklings treated with 12 mg methimazole 100 g(-1) body mass (0.109+/-0.047 TR:beta-actin ratio, P<0.05) compared with that in euthyroid controls (0.380+/-0.202), but was unaltered in the pectoralis and cardiac muscles. Expression of TR beta 0 mRNA was significantly higher in pectoralis (by 3.5-fold, P<0. 05), cardiac (by 4.2-fold, P=0.003) and leg (by 4.0-fold, P<0.001) muscles of ducklings treated with thyroid hormones compared with those in euthyroid controls (0.098+/-0.019, 0.822+/-0.297 and 0. 38+/-0.202 TR:beta-actin respectively). Only the pituitary gland expressed significant levels of TR beta 2 mRNA.

Free access

S Chan, CJ McCabe, TJ Visser, JA Franklyn, and MD Kilby

N-TERA-2 cl/D1 (NT2) cells, a human embryonal cell line with characteristics of central nervous system precursor cells, were utilised to study thyroid hormone action during early neuronal growth and differentiation. Undifferentiated NT2 cells expressed mRNAs encoding thyroid hormone receptors (TRs) alpha1, alpha2 and beta1, iodothyronine deiodinases types 2 (D2) and 3 (D3) (which act as the pre-receptor regulators), and the thyroid hormone-responsive genes myelin basic protein (MBP) and neuroendocrine specific protein A (NSP-A). When terminally differentiated into post-mitotic neurons (hNT), TRalpha1 and TRbeta1 mRNA expression was decreased by 74% (P=0.05) and 95% (P<0.0001) respectively, while NSP-A mRNA increased 7-fold (P<0.05). However, mRNAs encoding TRalpha2, D2, D3 and MBP did not alter significantly upon neuronal differentiation and neither did activities of D2 and D3. With increasing 3,5,3'-triiodothyronine (T(3)) concentrations, TRbeta1 mRNA expression in cultured NT2 cells increased 2-fold at 10 nM T(3) and 1.3-fold at 100 nM T(3) (P<0.05) compared with that in T(3)-free media but no change was seen with T(3) treatment of hNT cells. D3 mRNA expression in NT2 cells also increased 3-fold at 10 nM T(3) (P=0.01) and 2.4-fold at 100 nM T(3) (P<0.05) compared with control, but there was no change in D3 enzyme activity. In contrast there was a 20% reduction in D3 mRNA expression in hNT cells at 10 nM T(3) (P<0.05) compared with control, with accompanying reductions in D3 activity with increasing T(3) concentrations (P<0.05). There was no significant change in the expression of the TRalpha isoforms, D2, MBP and NSP-A with increasing T(3) concentrations in either NT2 or hNT cells. Undifferentiated NT2 and differentiated hNT cells show differing patterns of T(3)-responsiveness, suggesting that there are different regulatory factors operating within these cell types.