BACKGROUND CONTEXT-The therapeutic strategies that have thus far been employed for the treatment of intervertebral disc degeneration (IDD) have focused on relieving the symptoms, while reversal of the degeneration remains an important challenge for the effective treatment of IDD. Growth and differentiation factor-5 (GDF5), of which deficiency leads to early disc degeneration changes, has the potential to increase proliferation of disc cells and expression of extracellular matrix proteins.

We studied the regulation of mRNAs encoding the alpha- and beta-subunits of TSH by thyroid hormones (T4 and T3) in mouse thyrotropic tumors and pituitary glands. Hypothyroid male (LAF1) mice bearing thyrotropic tumor (TtT97) were injected daily with T4 for 0, 1, 5, 12, or 33 days. After day 33, plasma levels of TSH and free (unassociated) TSH beta-subunit were reduced to less than 1% of control levels, whereas free alpha-subunit was reduced to 6% of control levels. Steady state levels of subunit mRNAs in extracts of the thyrotropic tissues were measured by blot hybridization analyses using mouse subunit-specific cloned cDNAs. Treatment of mice with T4 caused a rapid decline in the levels of tumor mRNAs for both alpha and TSH beta; after day 1, alpha and TSH beta mRNA levels decreased to 35% and 10% of control values, respectively. Levels of TSH beta mRNA were undetectable after 5 days of T4 treatment, whereas levels of alpha-subunit mRNA remained at 30-35% of control levels even after day 33. In a separate experiment, TSH beta mRNA decreased to 42% of the control level (P less than 0.05), whereas alpha-subunit mRNA remained at 64% of the control level (P = NS) 4 h after a single injection of T4. Finally, T3 also caused a rapid decrease in the levels of both subunit mRNAs in the anterior pituitary glands of hypothyroid mice, but the effect was more complete on TSH beta mRNA levels. We conclude that thyroid hormones have rapid suppressive effects on the levels of mRNAs encoding the subunits of mouse TSH in the thyrotrope. The suppressive effects of thyroid hormones occur more rapidly and are greater for TSH beta than alpha-subunit mRNAs. The parallel changes observed in the subunit mRNA levels and the plasma subunit protein levels in animals treated with thyroid hormones suggest that the changes in the plasma levels of TSH and subunits may reflect effects of thyroid hormones on TSH gene expression in addition to effects on secretion.

We determined the occurrence of the single nucleotide polymorphisms (SNPs) -403A/G and -28C/G in the promoter region of RANTES in 1082 Chinese blood donors from northern and southern China and 249 HIV patients from southern China. Compared to healthy adults, Chinese AIDS patients had a significantly higher frequency of the -403G allele and haplotype I, -403G/-28C (P < 0.05), and a lower frequency of the -403A/A genotype (P < 0.01). Symptomatic patients had a higher frequency of the -28G allele and a lower frequency of the -28C/C genotype (P < or = 0.01). The plasma RANTES level was significantly lower in blood donors homozygous for haplotype I than in those who were homozygous for haplotypes II and III (P < 0.05). The frequency of the -403G allele was found to be higher in Chinese than in indigenous Africans, but lower than in Caucasians, Hispanics, and African Americans. The frequency of the -28G allele was comparable in Chinese and Japanese; this allele is rare in other ethnic groups. Results suggest that -403G may be associated with increased susceptibility to HIV infection, while -28G may be associated with advanced disease progression. The impact of SNPs on HIV infection appears to be unique in Chinese.