A crosstalk between bone and gonads.
ABSTRACT The sex steroid hormones testosterone and estrogen are essential determinants not only of reproductive functions but also for bone growth and the maintenance of skeletal integrity. The importance of this latter form of regulation is best exemplified by the fact that gonadal failure triggers bone loss in both genders and causes osteoporosis in postmenauposal women. Traditionally, bone physiology is studied with the view that the skeleton is simply a recipient of hormonal inputs. However, a richer picture of bone physiology has recently emerged, and it is now clear that the skeleton is an endocrine organ itself. This is particularly relevant to the interplay between bone and gonads because genetics and biochemical evidence have established that bone, via the osteoblast-derived hormone osteocalcin, promotes testosterone biosynthesis. This review will present the mechanism of action of osteocalcin and will discuss the implications of this novel regulation.
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ABSTRACT: Available evidence indicates that transforming growth factor beta (TGFbeta) is produced by bone cells, that production is enhanced by testosterone and dihydrotestosterone, and that TGFbeta is an important modulator of bone formation, induction, and repair. To determine the relative concentrations of isoforms of skeletal TGFbeta, whether orchiectomy alters the concentration of TGFbeta in long bones, and whether alteration is prevented by testosterone replacement, male Sprague-Dawley rats were either sham-operated and given placebo (n = 20) or orchiectomized and given either placebo (n = 20) or 100 mg testosterone (n = 20) by slow-release pellets implanted sc at the back of the neck and killed at 6 weeks. Orchiectomy did not change serum calcium and lowered serum testosterone and serum phosphorus; these reductions were prevented by testosterone replacement. TGFbeta1 in skeletal extracts was much more abundant than TGFbeta2 or TGFbeta3. Orchiectomy reduced skeletal TGFbeta by over 80 percent, and reduction was prevented by testosterone replacement. The relative abundance of the three isoforms of TGFbeta in bone was not influenced by orchiectomy or testosterone replacement, and skeletal messenger RNA of TGFbeta1 and TGFbeta2 was not altered 4 weeks after orchiectomy. Messenger RNA for TGFbeta3 was below the limits of detection. Thus, testosterone deficiency markedly diminishes skeletal TGFbeta, and reduction is prevented by testosterone replacement. The findings support the hypothesis that testosterone and TGFbeta are required for maintenance of the skeleton in male rats.Endocrinology 03/1998; 139(2):546-50. · 4.72 Impact Factor
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ABSTRACT: The effects of estrogen on bone are possibly mediated by several cell types. In the present study, the effect of 17beta-estradiol (E2) on osteoblast-like cells was investigated by using mouse bone marrow cultures. Bone marrow cells were harvested from the shafts of femurs of 10-week-old NMRI mice and cultured. On day 6, confluent primary cultures were trypsinized and subcultured. Under the conditions used (Keila, S., Pitaru, S., Grosskopf, A., and Wernreb, M. Bone marrow from mechanically unloaded rat bones expresses reduced osteogenic capacity in vitro. J Bone Miner Res 9:321-327; 1994), the bone marrow cultures showed differentiation towards the osteoblastic phenotype. This was demonstrated by the appearance of osteoblastic markers such as alpha1(I) collagen (COL1), alkaline phosphatase (ALP), osteocalcin (OCN), osteopontin (OP), and transforming growth factor-beta1 (TGFbeta1), which were detected by using reverse transcriptase polymerase chain reaction (RT-PCR). Bone nodule formation, including deposition of collagen fibers and matrix mineralization, was also studied at several time points of the 3-week culture period. The effect of E2 on the appearance of osteoblastic markers was studied by incubating cultures in the presence or absence of the hormone. The messenger ribonucleic acid (mRNA) for the estrogen receptor (ER) was found to be expressed at all time points as demonstrated by RT-PCR. When grown with E2, the rate of cell proliferation was increased in the early phase of cultures, but not after day 6. The addition of E2 in subcultures resulted in an increase of levels of mRNA for COL1, ALP, OCN, OP, and TGF-beta1. ALP activity was also increased. Bone nodule formation, as well as calcium contents, were significantly increased in the cultures grown in the presence of E2. All E2 concentrations used (0.01-10 nmol/L) were effective but the maximum response was obtained with 0.1 nmol/L E2. Addition of the antiestrogen ICI 182,780 abolished the E2-induced stimulation of proliferation and later an increase in ALP activity. Addition of ICI 182,780 without the hormone did not cause any changes when compared to control cultures. In conclusion, our results demonstrate that E2 stimulates sequential differentiation of osteoblasts and increases deposition and mineralization of matrix in mouse bone marrow cultures in an estrogen receptor-dependent manner.Bone 03/1998; 22(3):201-9. · 3.82 Impact Factor
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ABSTRACT: The incidence of distal forearm fractures peaks during the adolescent growth spurt, but the structural basis for this is unclear. Thus, we studied healthy 6- to 21-yr-old girls (n = 66) and boys (n = 61) using high-resolution pQCT (voxel size, 82 microm) at the distal radius. Subjects were classified into five groups by bone-age: group I (prepuberty, 6-8 yr), group II (early puberty, 9-11 yr), group III (midpuberty, 12-14 yr), group IV (late puberty, 15-17 yr), and group V (postpuberty, 18-21 yr). Compared with group I, trabecular parameters (bone volume fraction, trabecular number, and thickness) did not change in girls but increased in boys from late puberty onward. Cortical thickness and density decreased from pre- to midpuberty in girls but were unchanged in boys, before rising to higher levels at the end of puberty in both sexes. Total bone strength, assessed using microfinite element models, increased linearly across bone age groups in both sexes, with boys showing greater bone strength than girls after midpuberty. The proportion of load borne by cortical bone, and the ratio of cortical to trabecular bone volume, decreased transiently during mid- to late puberty in both sexes, with apparent cortical porosity peaking during this time. This mirrors the incidence of distal forearm fractures in prior studies. We conclude that regional deficits in cortical bone may underlie the adolescent peak in forearm fractures. Whether these deficits are more severe in children who sustain forearm fractures or persist into later life warrants further study.Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 01/2009; 24(6):1033-42. · 6.04 Impact Factor