Elevated thyroid-stimulating hormone (TSH) and hypercholesterolemia commonly coexist, as typically seen in hypothyroidism, but there is no known mechanism directly linking the two. Here, we demonstrated that in liver cells, TSH promoted the expression of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMGCR), a rate-limiting enzyme in cholesterol synthesis, by acting on the TSH receptor in hepatocyte membranes and stimulating the cyclic adenosine monophosphate / protein kinase A / cyclic adenosine monophosphate-responsive element binding protein (cAMP/PKA/CREB) signaling system. In thyroidectomized rats, the production of endogenous thyroid hormone was eliminated and endogenous TSH was suppressed through pituitary suppression with constant administration of exogenous thyroid hormone, and hepatic HMGCR expression was increased by administration of exogenous TSH. These results suggested that TSH could up-regulate hepatic HMGCR expression, which indicated a potential mechanism for hypercholesterolemia involving direct action of TSH on the liver. (HEPATOLOGY 2010;52:1401-1409 H ypothyroidism is well known to be associated with elevated serum TC, which can result in hypercholesterolemia. 1,2 The underlying mechanism is widely thought to be TH deficiency.However, elevation of serum TC has also been observed in patients with subclinical hypothyroidism (SCH), in which TSH is elevated but TH stays within its normal range. 1,3,4 Thus, the development of

The aim of this study was to investigate the osteoporosis prevalence and the risks of postmenopausal women and elderly men in Gansu province.This cross-sectional study involved 3359 postmenopausal women and 3205 elderly males who were randomly selected from 7 areas in Gansu province. Areal bone mineral density (BMD) (g/cm2) was measured at the distal one-third radius of the nonstressed forearm using dual-energy X-ray absorptiometry (DXA: Osteometer MediTech). Factors related to osteoporosis were analyzed.The prevalence of osteoporosis in the entire study population was 9.65% for postmenopausal women and 8.08% for elderly males by WHO criteria, while the rate of osteopenia were 27.09% for postmenopausal women and 26.68% for elderly males. Risk of osteoporosis was significantly associated with age, menopause age, duration of menopause, body mass index (BMI), educational level, and alcohol consumption in postmenopausal women. In elderly men, age, BMI, current smoking, alcohol consumption, physical activity, and sun exposure were associated with osteoporosis. The bone turnover markers osteocalcin (OC) and C-terminal cross-linked telopeptides of type I collagen (β-CTX) were inversely correlated with BMD in both genders; serum P and 25(OH)D found no significant correlation with BMD. Serum Ca showed a positive effect on BMD in elderly men only.The osteoporosis prevalence of postmenopausal women and the men aged over 60 years in Gansu province is presented. Risk of osteoporosis was significantly associated with age, menopause age, year since menopause, BMI, and educational level in postmenopausal women. In elderly men, age, BMI, and current smoking were associated with osteoporosis. This study also found that higher OC and β-CTX level were associated with lower BMD. Poor 25(OH)D, Ca, P status were not associated with an increased risk of low BMD.

The function of thyrotropin (TSH) in the thyroid gland is mediated by thyrotropin receptor (TSHR). In addition to the thyroid, TSHR expression has been described in some non-thyroidal tissues, although it is uncertain whether TSHR is present in hepatocytes. One study has reported hepatic expression of TSHR mRNA, but this was considered to be because of illegitimate transcription, and there has not been a study investigating its protein expression and function in hepatocytes. Here, we examined the expression of TSHR in human and rat liver tissues, as well as human normal hepatocyte cell line L-02. Our results demonstrated that hepatic TSHR mRNA could be detected and had the same sequence as that of thyroid-derived mRNA. TSHR protein was also expressed and mainly located in the hepatocyte cell membrane. Moreover, bovine TSH and immunoglobulin from sera of patients with Graves’ disease stimulated cAMP production in these cells. Taken together, these data show that TSHR is present and functional in hepatocytes, and this expression is not a case of illegitimate transcription. Given the pivotal role of the liver in body metabolism and many human diseases, our findings provide important implications for a potentially novel physiopathological role of TSH via acting on the TSHR in hepatocytes besides its classical role in regulating the thyroid function.