Search

Local production of prostaglandins by osteoblasts may be important in controlling the bone resorbing activity of some hormones which have receptors on osteoblasts. We have demonstrated that osteoblast-like cells derived from human bone can incorporate [14C]arachidonic acid into phospholipids and synthesise immunoreactive PGE. Parathyroid hormone increases both the release of incorporated arachidonic acid and the synthesis of PGE. This is the first demonstration of modulation of bone cell prostaglandin synthesis by a bone resorbing hormone.

BACKGROUND: Dietary iron intake is associated with bone metabolism in human and animals. Previous studies have suggested that iron deficiency diminishes bone formation and causes bone loss in rats, however, the detailed mechanisms remain unclear. To clarify the mechanism of the diminishing bone formation in iron deficiency, we examined the renal 25-hydroxyvitamin D3-1α-hydroxylase (1α-hydroxylase) activity and femoral expression of bone formation-related genes in iron-deficient rats. METHODS: Male Wistar rats (n = 18) at 3 weeks of age were divided into three groups of six rats each. Two groups of rats were given free access to a control diet or an iron-deficient diet for 4 weeks. Rats in the third group were pair-fed the control diet, calculated as the mean food intake of the iron-deficient group. RESULTS: Following the treatment, compared with the control and pair-fed groups, hemoglobin and liver iron concentrations were significantly lower and heart weight was significantly higher in the iron-deficient group. Serum 1,25-dihydroxyvitamin D3 concentration and renal 1α-hydroxylase activity were significantly lower in the iron-deficient group compared with the control and pair-fed groups. Serum osteocalcin concentration and bone mineral density of the femur were also significantly lower in the iron-deficient group compared with the control and pair-fed groups. Furthermore, iron-deficient diet decreased runt-related transcription factor 2, osteocalcin, and type I collagen mRNA expression in the femur. CONCLUSIONS: Our findings indicate that iron deficiency reduces renal 1α-hydroxylase activity, leading to a decreased bone formation in rats.

Background Aromatase converts testosterone into 17beta-estradiol in granulosa cells, and the converted 17beta-estradiol contributes to follicular maturation. Additionally, excessive testosterone inhibits aromatase activity, which can lead to concerns regarding polycystic ovary syndrome (PCOS). Generally, 1,25-dihydroxyvitamin D3 (1,25D3) supplements help to improve the symptoms of PCOS patients who exhibit low blood levels of 1,25D3. Therefore, this study investigated the interaction effects of 1,25D3 and testosterone on estrogenesis and intercellular connections in rat granulosa cells. Methods Primary cultures of granulosa cells were treated with testosterone or testosterone plus 1,25D3, or pre-treated with a calcium channel blocker or calcium chelator. Cell lysates were subjected to western blot analysis to determine protein and phosphorylation levels, and 17beta-estradiol secretion was examined using a radioimmunoassay technique. Cell viability was evaluated by MTT reduction assay. Connexin 43 (Cx43) mRNA and protein expression levels were assessed by qRT-PCR, western blot, and immunocytochemistry. Results Testosterone treatment (0.1 and 1 microg/mL) increased aromatase expression and 17beta-estradiol secretion, and the addition of 1,25D3 attenuated testosterone (1 microg/mL)-induced aromatase expression but improved testosterone-induced 17beta-estradiol secretion. Furthermore, testosterone-induced aromatase phosphotyrosine levels increased at 10 min, 30 min and 1 h, whereas 1,25D3 increased the longevity of the testosterone effect to 6 h and 24 h. Within 18–24 h of treatment, 1,25D3 markedly enhanced testosterone-induced 17beta-estradiol secretion. Additionally, pre-treatment with a calcium channel blocker nifedipine or an intracellular calcium chelator BAPTA-AM reduced 1,25D3 and testosterone-induced 17beta-estradiol secretion. Groups that underwent testosterone treatment exhibited significantly increased estradiol receptor beta expression levels, which were not affected by 1,25D3. Neither testosterone nor 1,25D3 altered 1,25D3 receptor expression. Finally, at high doses of testosterone, Cx43 protein expression was decreased in granulosa cells, and this effect was reversed by co-treatment with 1,25D3. Conclusions These data suggest that 1,25D3 potentially increases testosterone-induced 17beta-estradiol secretion by regulating aromatase phosphotyrosine levels, and calcium increase is involved in both 1,25D3 and testosterone-induced 17beta-estradiol secretion. 1,25D3 reverses the inhibitory effect of testosterone on Cx43 expression in granulosa cells.