Biomedical subjects

Liesbeth Vandenput

Publications and source records attributed to Liesbeth Vandenput.

5 recordsLinked to original sources

PubMed2007

Serum levels of specific glucuronidated androgen metabolites predict BMD and prostate volume in elderly men.

UNLABELLED: Androgens are important regulators of bone and prostate health in elderly men. The role of serum levels of glucuronidated androgen metabolites as predictors of BMD and prostate volume in men is unclear. We show that specific glucuronidated androgen metabolites predict BMD and prostate volume in elderly men. INTRODUCTION: Androgens are important regulators of bone and prostate health in elderly men. Local synthesis and degradation of androgens are likely to be important parameters of biological action of androgens in androgen-responsive tissues. The aim of this study was to determine the role of serum levels of glucuronidated androgen metabolites as predictors of BMD and prostate volume in elderly men. MATERIALS AND METHODS: A subsample of the population-based Swedish part of the MrOS study (n = 631, average age = 75.9 years) was investigated. Bone parameters were measured using DXA. Serum levels of total testosterone (T) and dihydrotestosterone (DHT) were measured by gas chromatography/mass spectroscopy (GC-MS); androstane-3alpha,17beta-diol-3glucuronide (3G) and androstane-3alpha,17beta-diol-17glucuronide (17G) were measured by liquid chromatography/mass spectroscopy. Prostate volume (n = 159) was measured by transrectal ultrasound. RESULTS: The general pattern is that two of the glucuronidated androgen metabolites, namely 17G and 3G, are stronger positive predictors of BMD than the bioactive androgens (T and DHT). In addition, 17G is a clear positive predictor of prostate volume, explaining 4.5% of the variance in prostate volume, whereas the bioactive androgens do not display any association with prostate volume. CONCLUSIONS: Serum levels of specific glucuronidated androgen metabolites predict BMD and prostate volume in elderly men. Future studies should determine if the glucuronidated androgen metabolites also reflect other biological correlates of androgenic activity, including prostate cancer, and if low levels might be a marker of general androgen deficiency in men.

Absorptiometry, Photon↗

PubMed2005

Bone and muscle protective potential of the prostate-sparing synthetic androgen 7alpha-methyl-19-nortestosterone: evidence from the aged orchidectomized male rat model.

This study reports the preclinical evaluation of the bone and muscle protective potential of the synthetic androgen 7alpha-methyl-19-nortestosterone (MENTtrade mark), as assessed in the aged orchidectomized rat model. Aged (13-month-old) orchidectomized Wistar rats were treated with different doses of MENT (4, 12 or 36 microg/day) subcutaneously for 16 weeks via mini-osmotic pumps. Analysis of the effects of androgen deficiency versus MENT replacement was performed using quantitative computed tomography (pQCT), dual energy X-ray absorptiometry (DEXA) and biochemical markers of bone turnover. At the end of the study period, prostate weight in orchidectomized rats treated with low- (4 microg/day) or mid-dose (12 mug/day) MENT remained significantly lower compared to the sham-operated animals (-47% and -25%, respectively). High-dose MENT (36 microg/day), on the other hand, induced prostate hypertrophy (+21% versus sham). Low-, mid- and high-dose MENT were found to be effective in suppressing the acceleration of bone remodeling following orchidectomy, as assessed by osteocalcin and deoxypyridinoline. In addition, low-, mid- and high-dose were able to prevent the orchidectomy-induced bone loss, as evaluated by DEXA at the femur and total-body and by pQCT at the femur. Compared to sham-operated animals, the low- and mid-dose MENT groups showed no decline in lean body mass and no muscle atrophy (as measured by m. quadriceps weight) at 16 weeks, whereas high-dose MENT was associated with a significant decline in lean body mass (-8.5% versus sham) and quadriceps weight (-10.6%). We conclude that, in the aged orchidectomized rat model, low- and mid-doses of the synthetic androgen MENT have bone and muscle protective effects and do not induce prostate hypertrophy. The bone protective action of high-dose MENT, however, occurs at the expense of muscle wasting and prostate hypertrophy. Our findings support the need for human studies to explore the potential of MENT as an option for androgen replacement in aging men.

Absorptiometry, Photon↗

PubMed2005

Reversing sex steroid deficiency and optimizing skeletal development in the adolescent with gonadal failure.

During puberty, the acquisition of skeletal mass and areal bone mineral density (BMD) mainly reflects an increase in bone size (length and perimeters) and not true volumetric BMD. Sexual dimorphism in bone mass and areal BMD is also explained by differences in bone size (longer and wider bones in males) and not by differences in volumetric BMD. Androgens stimulate skeletal growth by activation of the androgen receptor, whereas estrogens (following aromatization of androgens and stimulation of estrogen receptors) have a biphasic effect on skeletal growth during puberty. Recent evidence from clinical cases has shown that many of the growth-promoting effects of the sex steroids are mediated through estrogens rather than androgens. In addition, skeletal maturation and epiphyseal fusion are also estrogen-dependent in both sexes. Nevertheless, independent actions of androgens in these processes also occur. Both sex steroids maintain volumetric BMD during puberty. Androgens interact with the growth hormone (GH)-insulin-like growth factor-I (IGF-I) axis neonatally, resulting in a sexual dimorphic GH pattern during puberty, whereas estrogens stimulate GH and hereby IGF-I in both sexes. Hypogonadism in adolescents impairs not only bone size but also maintenance of volumetric BMD, hereby severely reducing peak areal BMD. Delayed puberty in boys and Turner's syndrome in women impair both bone length and size, reducing areal BMD. Whether volumetric BMD is also reduced and whether fracture risk is increased in these conditions remains controversial. Replacing sex steroids according to a biphasic pattern (starting at low doses and ending at high-normal doses) seems the safest approach to reach targeted height and to optimize bone development.

Adolescent↗

PubMed2004

Role of the androgen receptor in skeletal homeostasis: the androgen-resistant testicular feminized male mouse model.

UNLABELLED: The role of androgen receptor-mediated androgen action on bone was investigated in testicular feminized male (Tfm) mice. Cortical bone was found to be unresponsive to testosterone (T) in orchidectomized Tfm mice, whereas cortical thickness as well as trabecular BMD and structure were fully maintained by T in the corresponding Tabby control mice. These data show an essential role for androgen receptor-mediated androgen action in periosteal bone formation. INTRODUCTION: Androgens can affect the male skeleton both directly-through activation of the androgen receptor (AR)-and indirectly-through stimulation of estrogen receptors after aromatization. We assessed the importance of AR-mediated androgen action on bone in a mouse model of androgen resistance. MATERIALS AND METHODS: Eight-week-old androgen-resistant testicular feminized male (Tfm) and Tabby control mice were orchidectomized (ORX) and treated for 4 weeks with a slow-release testosterone (T) pellet (delivering 167 microg/day) or a placebo pellet. A comprehensive analysis of the skeletal effects of androgen deficiency and replacement was performed using histomorphometry, QCT, and biochemical assessment of bone turnover. RESULTS: As expected, T increased trabecular BMD, volume, number, and width in ORX Tabby mice. In ORX Tfm mice, however, T had less effect on trabecular BMD and no effect on trabecular bone structure. T action on trabecular bone was associated with opposite changes in bone turnover: trabecular and endocortical bone turnover and serum levels of osteocalcin were all reduced by T in ORX Tabby mice, but not in ORX Tfm mice. T also increased cortical thickness (+16%), area, and density in ORX Tabby mice, but not in Tfm mice, resulting in greater bone strength in the Tabby control strain. The positive effects of T on cortical bone reflected a stimulatory effect on periosteal bone formation (+137%), which was again absent in Tfm mice. CONCLUSIONS: These data show that, in male mice, AR-mediated T action is essential for periosteal bone formation and contributes to trabecular bone maintenance.

Androgen-Insensitivity Syndrome↗

PubMed2004

Androgens and bone.

Loss of estrogens or androgens increases the rate of bone remodeling by removing restraining effects on osteoblastogenesis and osteoclastogenesis, and also causes a focal imbalance between resorption and formation by prolonging the lifespan of osteoclasts and shortening the lifespan of osteoblasts. Conversely, androgens, as well as estrogens, maintain cancellous bone mass and integrity, regardless of age or sex. Although androgens, via the androgen receptor (AR), and estrogens, via the estrogen receptors (ERs), can exert these effects, their relative contribution remains uncertain. Recent studies suggest that androgen action on cancellous bone depends on (local) aromatization of androgens into estrogens. However, at least in rodents, androgen action on cancellous bone can be directly mediated via AR activation, even in the absence of ERs. Androgens also increase cortical bone size via stimulation of both longitudinal and radial growth. First, androgens, like estrogens, have a biphasic effect on endochondral bone formation: at the start of puberty, sex steroids stimulate endochondral bone formation, whereas they induce epiphyseal closure at the end of puberty. Androgen action on the growth plate is, however, clearly mediated via aromatization in estrogens and interaction with ERalpha. Androgens increase radial growth, whereas estrogens decrease periosteal bone formation. This effect of androgens may be important because bone strength in males seems to be determined by relatively higher periosteal bone formation and, therefore, greater bone dimensions, relative to muscle mass at older age. Experiments in mice again suggest that both the AR and ERalpha pathways are involved in androgen action on radial bone growth. ERbeta may mediate growth-limiting effects of estrogens in the female but does not seem to be involved in the regulation of bone size in males. In conclusion, androgens may protect men against osteoporosis via maintenance of cancellous bone mass and expansion of cortical bone. Such androgen action on bone is mediated by the AR and ERalpha.

Androgens↗