Biomedical subjects

H Kaji

Publications and source records attributed to H Kaji.

At least 19 recordsLinked to original sources

PubMed2006

Serum levels of insulin-like growth factor (IGF); IGF-binding proteins-3, -4, and -5; and their relationships to bone mineral density and the risk of vertebral fractures in postmenopausal women.

We previously found that serum levels of insulin-like growth factor I (IGF-I) and IGF-binding protein (IGFBP)-3, but not IFGBP-2, were associated with bone mineral density (BMD) and the risk of vertebral fractures. The aim of the present study was to investigate the roles of IGFBP-4 and -5 in age-dependent bone loss and vertebral fracture risk in postmenopausal Japanese women and to compare them with those of IGF-I and IGFBP-3. One hundred and ninety-three Japanese women aged 46-88 years (mean 62.5) were enrolled in the cross-sectional study. BMD was measured at the lumbar spine, femoral neck, ultradistal radius (UDR), and total body by dual-energy X-ray absorptiometry. Serum levels of IGFBP-4 and -5 as well as IGF-I and IGFBP-3 were measured by radioimmunoassay. Serum levels of IGF-I, IGFBP-3, and IGFBP-5 declined with age, while serum IGFBP-4 increased with age. Multiple regression analysis was performed between BMD at each skeletal site and serum levels of IGF-I and IGFBPs adjusted for age, body weight, height, and serum creatinine. BMD at the UDR was significantly and positively correlated with all serum levels of IGF-I and IGFBPs measured (P < 0.01), while BMD at the femoral neck was correlated with none of them. Serum IGF-I level was significantly and positively correlated with BMD at all sites except the femoral neck (P < 0.01), while serum IGFBP-3 and -4 levels were significantly and positively correlated with only radial BMD (P < 0.01). Serum IGFBP-5 level was positively correlated with UDR BMD (P < 0.001) and negatively correlated with total BMD (P < 0.05). Serum IGF-I, IGFBP-3, and IFGBP-5 levels were significantly lower in women with vertebral fractures than in those without fractures (mean +/- SD: 97.1 +/- 32.1 vs. 143.9 +/- 40.9 ng/dl, P < 0.0001; 2.18 +/- 1.02 vs. 3.23 +/- 1.07 microg/ml, P < 0.0001; 223.6 +/- 63.3 vs. 246.5 +/- 71.5 ng/ml, P = 0.0330, respectively). When multivariate logistic regression analysis was performed with the presence of vertebral fractures as a dependent variable and serum levels of IGF-I and IGFBPs adjusted for age, body weight, height, serum creatinine, and serum alubumin as independent variables, IGF-I and IGFBP-3 were selected as indices affecting the presence of vertebral fractures [odds ratio (OR) = 0.29, 95% confidential interval (CI) 0.15-0.57 per SD increase, P = 0.0003 and OR = 0.31, 95% CI 0.16-0.61 per SD increase, P = 0.0007, respectively]. To compare the significance values, IGF-I, IGFBP-3, and age were simultaneously added as independent variables in the analysis. IGFBP-3 was more strongly associated with the presence of vertebral fractures than IGF-I and age (P = 0.0006, P = 0.0148, and P = 0.0013, respectively). Thus, after comprehensive measurements of serum levels of IGF-I and IGFBPs, it seems that serum IGF-I level is most efficiently associated with bone mass and that serum IGFBP-3 level is most strongly associated with the presence of vertebral fractures in postmenopausal women among the IGF system components examined.

Aged↗

PubMed2006

Serum soluble factors induce the proliferation, alkaline phosphatase activity and transforming growth factor-beta signal in osteoblastic cells in the patient with hepatitis C-associated osteosclerosis.

Hepatitis C-associated osteosclerosis (HCAO) is a rare syndrome characterized by severe, acquired, generalized osteosclerosis and hyperostosis in adults who are infected with the hepatitis C virus. However, the detail of the pathogenesis of HCAO is still unknown. We examined the effects of serum of the HCAO patient on the proliferation, alkaline phosphatase (ALP) activity and transforming growth factor (TGF)-beta-Smad signaling in mouse osteoblastic cells. The patient was compatible with HCAO, characterized by high bone mass, bone thickening and bone pain with normal lamelar bone. The serum from the HCAO patient increased the levels of TGF-beta and Smad3 expression in osteoblastic MC3T3-E1 cells, compared with the control subject. Moreover, the serum from the HCAO patient significantly augmented TGF-beta-induced transcriptional activity with luciferase assay using 3TP-Lux with a Smad3-specific responsive element. In addition, the serum from the HCAO patient significantly stimulated the MTT intensity, the level of proliferating cell nuclear antigen expression, a proliferation marker, and ALP activity in MC3T3-E1 cells, compared with that from the control subject. In conclusion, the present study indicated that the serum from the HCAO patient stimulated TGF-beta-Smad signaling, as well as the proliferation and ALP activity in osteoblastic cells. Some soluble factors other than parathyroid hormone might be related to the pathogenesis of HCAO.

3T3 Cells↗

PubMed2006

The usefulness of bone metabolic indices for the prediction of changes in bone mineral density after parathyroidectomy in patients with primary hyperparathyroidism.

Patients with primary hyperparathyroidism (pHPT) have reduced bone mineral density (BMD). Although pHPT causes high bone turnover, the exact metabolic bone markers useful for predicting changes in BMD after parathyroidectomy (PTX) remain elusive. The present study was performed to examine the relationship between bone metabolic indices and BMD changes after PTX in 29 pHPT Japanese patients, which received PTX successfully. BMD values were measured by dual-energy X-ray absorptiometry in the lumbar spine and distal one third of radius. As for bone metabolic indices, serum bone-type alkaline phosphates (BAP), serum osteocalcin (OCN), urinary deoxypiridinoline (Dpd), and urinary type I collagen cross-linked N-telopeptides (NTX) were measured. The study included 10 male and 19 female patients (17 postmenopausal). Urinary Dpd, but not NTX was significantly correlated with serum BAP and OCN. Either bone formation or bone resorption indices were significantly and highly correlated with Z-score of BMD in the radius, but not at lumbar spine. Urinary Dpd was significantly correlated with BMD changes at both lumbar spine and radius and at all time points over the two years after PTX. These correlations were most potent among bone metabolic indices in this study. The measurement of urinary Dpd would be useful for predicting long-term changes in BMD at radial and lumbar spine after PTX than other bone metabolic indices.

Bone Density↗

PubMed2006

Smad3 differently affects osteoblast differentiation depending upon its differentiation stage.

Smad3, a critical component of the TGF-beta signaling pathways, plays an important role in the regulation of bone formation. However, how Smad3 affects osteoblast at the different differentiation stage remains still unknown. In the present study, we examined the effects of Smad3 on osteoblast phenotype by employing mouse bone marrow ST-2 cells and mouse osteoblastic MC3T3-E1 cells at the different differentiation stage. Smad3 overexpression significantly inhibited bone morphogenetic protein-2 (BMP-2)-induced ALP activity in ST-2 cells, indicating that Smad3 suppresses the commitment of pluripotent mesenchymal cells into osteoblastic cells. Smad3 increased the levels of COLI and ALP mRNA at 7 day cultures in MC3T3-E1 cells, and its effects on COL1 were decreased as the culture periods progress, although its effects on ALP were sustained during 21 day cultures. Smad3 overexpression enhanced the level of Runx2 and OCN mRNA at 14 day and 21 day cultures. Smad3 increased the levels of MGP and NPP-1 mRNA, although the extent of increase in MGP and NPP-1 was reduced and enhanced during the progression of culture period, respectively. Smad3 did not affect the level of ANK mRNA. On the other hand, Smad3 enhanced the level of MEPE mRNA at 14 and 21 day cultures, although Smad3 decreased it at 7 day cultures. In conclusion, Smad3 inhibits the osteoblastic commitment of ST-2 cells, while promotes the early stage of differentiation and maturation of osteoblastic committed MC3T3-E1 cells. Also, Smad3 enhanced the expression of mineralization-related genes at the maturation phase of MC3T3-E1 cells.

3T3 Cells↗

PubMed2006

Bronchogenic glomangiomyoma with local intravenous infiltration.

Most glomus tumours occur in the dermis and subcutaneous tissues. Lung glomus tumours are quite rare. The current authors present the first reported case of a lung-derived glomangiomyoma, the rarest variant of glomus tumour. A 56-yr-old female was admitted with haemoptysis. Chest computed tomography showed an approximately 5-cm-diameter mass in the right lower lobe with mucoid impaction. After a right lower lobectomy, a diagnosis of glomangiomyoma was made. The tumour had grown endobronchially and its maximal diameter was 5.5 cm. Although cytologically benign, glomus tumour cells had visibly infiltrated neighbouring vessels. These results suggest that a bronchogenic glomangiomyoma has a low-grade malignancy potential and warrants close follow-up.

Carcinoma, Bronchogenic↗

PubMed2005

Body composition and vertebral fracture risk in female patients treated with glucocorticoid.

INTRODUCTION: Glucocorticoid (GC) causes bone loss and an increase in bone fragility. However, fracture risk was found to be only partly explained by bone mineral density in GC-treated patients (GC patients). Although GC causes a change in the distribution of fat in the body, the relationship between body composition and fracture risk in GC patients remains unknown. METHODS: The present study examined the relationship between the presence or absence of vertebral fractures and various indices, including body composition, in 92 premenopausal GC patients, 122 postmenopausal GC patients and 122 postmenopausal age-matched control subjects. Dual-energy X-ray absorptiometry was employed to analyze body composition. RESULTS: Percentage lean body mass (LBM), % fat and % trunk fat were not significantly different between postmenopausal GC patients and the control women. When groups with and without vertebral fractures were compared, % LBM and % fat were significantly higher and lower in groups with vertebral fractures, respectively, in postmenopausal GC patients, but not in the postmenopausal control women, although % trunk fat was not significantly different between groups with and without vertebral fractures. Femoral neck BMD was negatively correlated with % LBM and positively correlated with % fat. In premenopausal GC patients, % trunk fat was significantly higher in the fracture group, although % LBM and % fat were not significantly different between groups with and without vertebral fractures. CONCLUSION: The present study revealed that body composition is related to vertebral fracture risk in GC-treated patients. Lower % fat can be included in the determination of vertebral fractures in postmenopausal GC-treated patients. The influence of body composition on vertebral fracture risk may be different between the pre- and postmenopausal state in GC patients.

Absorptiometry, Photon↗

PubMed2005

Menin and TGF-beta superfamily member signaling via the Smad pathway in pituitary, parathyroid and osteoblast.

PITUITARY: Menin is a Smad3-interacting protein; inactivation of menin blocks transforming growth factor (TGF)-beta and activin signaling, antagonizing their growth-inhibitory properties in anterior pituitary cells. Menin is also required for the activin-induced inhibition of prolactin expression mediated by the Smads and the transcription factor, Pit-1. The interaction between menin and Smad3 is direct. PARATHYROID: In cultured parathyroid cells from uremic hemodialysis patients, in which the menin signaling pathways are probably still intact, menin inactivation achieved by menin antisense oligonucleotides leads to loss of TGF-beta inhibition of parathyroid cell proliferation and parathyroid hormone (PTH) secretion. Moreover, TGF-beta does not affect the proliferation and PTH production of parathyroid cells from multiple endocrine neoplasia type 1 (MEN1) patients. OSTEOBLAST: Men1-null mouse fetuses that die at day 12 or earlier have cranial/facial hypoplasias implicating menin in bone development. Menin is required for the commitment of multipotential mesenchymal stem cells into the osteoblast lineage. This is achieved by menin interacting physically and functionally with bone morphogenetic protein (BMP)-2 regulated Smads, such as Smad1 and Smad5, and the key osteoblast regulator, Runx2. These interactions are lost as the committed osteoblasts differentiate further at which time menin interacts with Smad3, mediating the negative regulation of Runx2 by TGF-beta. Menin also suppresses osteoblast maturation, partly by inhibiting the differentiation actions of JunD.

Animals↗

PubMed2005

Statins modulate the levels of osteoprotegerin/receptor activator of NFkappaB ligand mRNA in mouse bone-cell cultures.

Statins stimulate bone formation partly by inducing osteoblast differentiation, although there is controversy about the effects of statins on bone mineral density and fracture risk. Several studies have revealed that statins suppress bone resorption. However, the mechanism by which statins inhibit bone resorption is still unclear. The present study was performed to clarify the effects of statins on osteoclast formation as well as the levels of osteoprotegerin (OPG) and receptor activator of NFkappaB ligand (RANKL) mRNA in mouse bone-cell cultures by semiquantitative RT-PCR. 10(-8) M 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] significantly stimulated osteoclast formation and 10(-6) M statins (mevastatin and simvastatin) significantly antagonized osteoclast formation stimulated by 1,25(OH)2D3 in mouse bone-cell cultures, including both osteoblasts and osteoclasts. 10(-6) M mevastatin and simvastatin increased the level of OPG mRNA in mouse bone-cell cultures. On the other hand, 10(-6) M mevastatin and simvastatin inhibited the level of RANKL mRNA in these cultures. In conclusion, the present study demonstrates that statins inhibit osteoclast formation in mouse bone-cell cultures. Moreover, statins also increased and decreased the levels of OPG and RANKL mRNA expression in these cultures, respectively. The modulation of OPG/RANKL may be involved in the inhibition of osteoclast formation by statins.

Animals↗

PubMed2004

Testosterone increases osteoprotegerin mRNA expression in mouse osteoblast cells.

The role that androgens play in the regulation of bone metabolism has been substantiated in animals and humans. We previously demonstrated that testosterone inhibits osteoclast differentiation stimulated by parathyroid hormone through the androgen receptor in mouse bone-cell cultures. However, the details of this mechanism are still unknown. The present study was aimed at examining whether testosterone would affect the mRNA levels of osteoprotegerin (OPG) and receptor activator of Nf kappa B ligand (RANKL) in mouse bone-cell cultures as well as mouse osteoblastic cell-line, MC3T3-E1 cells by employing semi-quantitative RT-PCR. Testosterone increased OPG mRNA expression in both mouse bone-cell cultures and MC3T3-E1 cells. 10-8 M PTH-(1-34) as well as 10-8M 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] inhibited OPG mRNA expression in mouse bone cells. 10-8 M testosterone antagonized OPG mRNA expression inhibited by 10-8 M PTH-(1-34), but failed to affect OPG mRNA expression inhibited by 10-8 M 1,25(OH)2D3. 10-8 M alpha-dehydrotestosterone, a non-aromatizable androgen, increased OPG mRNA expression. On the other hand, testosterone did not affect RANKL mRNA expression in MC3T3-E1 or mouse bone cells. In conclusion, the present study demonstrated that testosterone increased OPG mRNA expression in mouse bone-cell cultures and the osteoblastic cell line. These effects are likely to take place through the androgen receptor.

Animals↗

PubMed2004

A novel splice site mutation of the thiazide-sensitive NaCl cotransporter gene in a Japanese patient with Gitelman syndrome.

Gitelman syndrome (GS, MIM 263800) is an inherited disorder characterized by metabolic alkalosis with hypokalemia, hypomagnesemia, and hypocalciuria. The genetic abnormalities causing GS are known to lie in the thiazide-sensitive NaCl cotransporter (TSC), which is expressed in the distal tubule of the kidney. The TSC gene, located at chromosome 16, consists of 26 exons and encodes the protein containing 12 putative transmembrane domains with long intracellular amino and carboxy termini. Most of the abnormalities identified in GS were missense mutations, distributed throughout the TSC gene without a hot spot. A 42-year-old Japanese man was introduced for close examination of hypokalemia. In renal clearance studies using furosemide or thiazide, chloride clearance was increased after furosemide but not after thiazide administration. Furthermore, the distal fractional chloride reabsorption was dramatically decreased by furosemide but not thiazide administration, suggesting a defect in the distal tubule. We then analyzed the TSC gene to confirm the diagnosis of GS, and identified a novel G to T mutation at the acceptor splice site preceding exon 14, resulting in disruption of a conventional 3'AG consensus splice site. Abnormal splicing by this mutation is predicted to cause the formation of truncated TSC with a partial deletion of the transmembrane domain, which will loose the function of transporter. In conclusion, we have identified a unique novel splice site mutation of the TSC gene in GS. The predicted structure of this mutant TSC can conceivably cause an impairment of the transporter activity and thereby be responsible for the development of GS in our patient.

Adult↗

PubMed2003

Lactogenic hormone responsive element reporter gene activation assay for human growth hormone.

We investigated the bioactivity of GH and compared with their immunoactivity in GH bioassay system using lactogenic hormone responsive element (LHRE) reporter gene in Chinese hamster ovary cells transiently co-transfected with human GH receptor cDNA and LHRE/TK-luciferase reporter gene (LHRE/Luc). The recombinant and serum GH but not prolactin almost equally were able to induce LHRE/Luc in a significant and dose-dependent manner, which were equally suppressed by anti-GH. Recombinant GH binding protein (GHBP) at 100 ng/ml but not at 20 ng/ml slightly attenuated GH-induced LHRE/Luc. The serum GH bioactivity (ng/ml) in patients with acromegaly were equal near to their immunoactivity, whereas the bioactivity of the serum GH in a short child with mutant GH (R77C) revealed lower than their immunoactivity. The bioactivity of the recombinant mutant GH was as half as that of wild type GH, thus confirming an antagonistic property of mutant GH. LHRE reporter gene activation assay is useful to measure the GH bioactivity in addition to the conventional bioassay using cell proliferation.

Animals↗

PubMed2003

Effect of parathyroidectomy on bone mineral density in hemodialysis patients with secondary hyperparathyroidism: possible usefulness of preoperative determination of parathyroid hormone level for prediction of bone regain.

PURPOSE: To examine longitudinal changes of bone mineral density (BMD) after parathyroidectomy (PTx) in patients undergoing maintenance hemodialysis (HD) with severe secondary hyperparathyroidism (HPT) to determine which factor contributes most to bone changes. METHODS: Fifteen Japanese HD patients who had been refractory to medical therapy were subject to PTx with autotransplantation. We measured BMD by dual energy X-ray absorptiometry (DXA) at the lumbar spine (L2 - 4 BMD) and the distal 1/3 region of the radius (1/3R BMD) at 1, 3, 6, 12, 24, and 36 months after PTx. RESULTS: Baseline Z-score of BMD was markedly low at 1/3R (- 3.07) and slightly low at L2 - 4 (-0.59) in this group. A significant increase in L2 - 4 BMD was observed as early as one month after PTx, which was sustained afterwards. Annual percent changes in L2 - 4 and 1/3R BMD were + 15.6 % and + 6.4 %, respectively. The annual percent changes in BMD at both sites were positively associated with preoperative intact PTH levels (L2 - 4; r = 0.642, p = 0.010, 1/3R; r = 0.884, p < 0.001) and total alkaline phosphatase (ALP) levels (L2 - 4; r = 0.663, p = 0.007, 1/3R; r = 0.858, p < 0.001). Stepwise multiple regression analysis revealed that serum levels of intact PTH and ALP were the best predictors of both percentage and net changes in radial BMD with high determination coefficients (r 2 > 0.8). CONCLUSION: Successful PTx following appropriate supplementation with vitamin D and calcium provides a marked increase in lumbar BMD and a modest increase in radial BMD in HD patients with secondary HPT. Preoperative levels of PTH and ALP are useful for predicting postoperative changes in bone mass.

Absorptiometry, Photon↗

PubMed2001

[Survey on opinions among employers regarding special health examinations in small-scale enterprises].

In order to clarify the employers' opinions regarding special health examinations and follow-up measures, we conducted a survey targeting small-scale enterprises that had less than fifty employees and no obligation to assign an occupational physician. We received 354 answers, a response rate of 49.5%. More than 60% of the employers felt that the special health examination was useful for preventing occupational diseases and for the health promotion of employees, and 83.9% of employers felt that the special health examinations were effective. On the other hand, about 30% of the employers felt that it was difficult to allocate a time and pay financial costs for special health examinations. The limited number of employees and financial restriction might prohibit them from carrying out and performing appropriate follow-up measures after the special health examination. Only 21.2% of enterprises had an occupational physician, 44.7% of employers had no information regarding the local occupational health service center, 51.4% of employers did not request an opinion related to employee's health problems after health examination. We concluded that it is important to build a social system to give employers information on where and how they may find sufficient medical resources for the effective application of the special health examination in small-scale enterprises.

Attitude to Health↗

PubMed2001

Hormonal regulation of the human ghrelin receptor gene transcription.

The aim of this study is to clarify the hormonal regulation of the human ghrelin receptor gene expression in GH(3) cells transfected with our previously cloned 5'-flanking region inserted into a luciferase reporter vector. Phorbor 12-tetradecanoate 13-acetate (TPA) with simultaneous addition of Bay K8644 mimicking ghrelin action caused a significant inhibition of the luciferase activity through the ghrelin receptor gene upstream proximal to -669 but not to -608 base pairs (bp). Glucocorticoid caused a weak but significant inhibition of the luciferase activity through the ghrelin receptor gene upstream proximal to -531 but not to -475 bp. Electrophoretic mobility shift assay resulted in binding of oligonucleotides between -669 and -640 bp, and between -520 and -491 bp to GH(3) cell nuclear proteins unlike AP(2) or glucocorticoid receptor. These results suggest that both TPA/Bay K8644 and glucocorticoid downregulate human ghrelin receptor gene expression through the transcriptional mechanism involving some nuclear factors.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed2001

Dual action of eicosapentaenoic acid in hepatoma cells: up-regulation of metabolic action of insulin and inhibition of cell proliferation.

Exogenous administration of eicosapentaenoic acid (EPA) improves insulin sensitivity, but its precise mechanism remains unknown. Here we show that EPA stimulates the intracellular insulin signaling pathway in hepatoma cells. Exposure of these cells to EPA caused up-regulation of several insulin-induced activities including tyrosine phosphorylation of insulin receptor substrate-1, insulin receptor substrate-1-associated phosphatidylinositol 3-kinase, and its downstream target Akt kinase activity as well as down-regulation of gluconeogenesis. In contrast, EPA decreased mitogen-activated protein kinase activity and inhibited cell proliferation. These findings raise the possibility that EPA up-regulates metabolic action of insulin and inhibits cell growth in humans.

Adaptor Proteins, Signal Transducing↗

PubMed2001

Upregulation of the klotho gene expression by thyroid hormone and during adipose differentiation in 3T3-L1 adipocytes.

A defect in the klotho gene expression in mice leads to a syndrome resembling human aging. The klotho gene encodes a single membrane protein whose extracellular domain carries homology to beta-glucosidases. However, either its function or regulatory mechanism of the gene expression still remains unknown. In the present study, we investigated the klotho gene expression in 3T3-L1 adipocytes using quantitative reverse transcription-polymerase chain reaction. Both membrane and secreted forms of the klotho gene were expressed in 3T3-L1 preadipocytes. Accompanied with adipose differentiation, not the secreted form but the membrane form was gradually increased. In 3T3-L1 adipocytes, triiodothyronine significantly increased the expression levels of membrane form of the klotho gene. These results suggest that the expression of membrane and secreted forms of klotho transcripts are regulated by different mechanisms and that the klotho gene product may play a role in adipose differentiation.

3T3 Cells↗

PubMed2001

Inactivation of menin, a Smad3-interacting protein, blocks transforming growth factor type beta signaling.

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by endocrine tumors of parathyroids, pancreatic islets, and anterior pituitary. The MEN1 gene encodes a nuclear protein called menin. In MEN1 carriers inactivating mutations give rise to a truncated product consistent with menin acting as a tumor suppressor gene. However, the role of menin in tumorigenesis and its physiological functions are not known. Here, we show that menin inactivation by antisense RNA antagonizes transforming growth factor type beta-mediated cell growth inhibition. Menin interacts with Smad3, and antisense menin suppresses transforming growth factor type beta-induced and Smad3-induced transcriptional activity by inhibiting Smad3/4-DNA binding at specific transcriptional regulatory sites. These results implicate a mechanism of tumorigenesis by menin inactivation.

Active Transport, Cell Nucleus↗

PubMed2001

Testosterone inhibits osteoclast formation stimulated by parathyroid hormone through androgen receptor.

Androgens play an important role in the regulation of bone metabolism in animals and humans. The present study was performed to investigate whether androgens would affect osteoclast formation stimulated by parathyroid hormone (PTH) in mouse bone cell cultures and its mechanism. Testosterone as well as alpha-dihydrotestosterone (DHT) concentration-dependently inhibited osteoclast formation induced by PTH-(1-34). 10(-8) M ICI 182780, an estrogen receptor inhibitor, did not affect PTH-induced osteoclast formation antagonized by 10(-8) M testosterone, although it completely antagonized the effects of 10(-8) M 17beta-estradiol. Moreover, 3 microM 4-androsten-4-ol-3,17-dione, an aromatase inhibitor, did not affect PTH-induced osteoclast formation antagonized by testosterone. Hydroxyflutamide, an androgen receptor antagonist, concentration-dependently antagonized the inhibitory effects of testosterone as well as DHT on PTH-stimulated osteoclast formation. In conclusion, the present study first demonstrated that testosterone inhibited osteoclast formation stimulated by PTH through the androgen receptor, but not through the production of intrinsic estrogen in mouse bone cell cultures.

Androgen Antagonists↗