Biomedical subjects

J M Janssen

Publications and source records attributed to J M Janssen.

5 recordsLinked to original sources

PubMed1999

Estradiol formation by human osteoblasts via multiple pathways: relation with osteoblast function.

The importance of estrogens in bone metabolism is illustrated by the accelerated bone loss and increase in osteoporotic fractures associated with postmenopausal estrogen deficiency. In this study, the expression and activity of the enzymes involved in estrogen metabolism in human osteoblastic cells were investigated in relation to differentiation of these cells. PCR reactions using mRNA from an in vitro differentiating human cell line (SV-HFO) were performed to assess mRNA expression of the enzymes aromatase, different subtypes of 17beta-hydroxysteroid dehydrogenase (17beta-HSD), and steroid sulfatase. Aromatase, sulfatase, and 17beta-HSD type 2 and 4 were found to be expressed throughout differentiation. Expression of 17beta-HSD type 3, however, was relatively weak, except for early time points in differentiation. Type 1 17beta-HSD expression was not detected. Aromatase activity decreased during differentiation, as was demonstrated by the conversion of androstenedione (A) and testosterone (T) into estrone (E(1)) and estradiol (E(2)), respectively. The 17beta-HSD isozymes catalysing a reductive reaction convert androstenedione and estrone into testosterone and estradiol, respectively. Their activity declined with differentiation. Analysis of 17beta-HSD activity indicated both oxidative (E(2) to E(1); T to A) and reductive (E(1) to E(2); A to T) metabolism at all stages of osteoblast differentiation. Both activities declined as cells moved toward a differentiating mineralizing phenotype. However, the oxidative reaction was increasingly in favor of the reductive reaction at all times during differentiation. Sulfatase activity, as demonstrated by the conversion of estrone-sulfate into estrone, was constant during differentiation. In conclusion, we have demonstrated that all enzymes necessary for estrogen metabolism are expressed and biologically active in differentiating human osteoblasts. The activity of aromatase and 17beta-HSD was found to be dependent on the stage of cell differentiation. In addition, human osteoblasts effectively convert estradiol into estrone. The efficacy of osteoblasts to synthesize estradiol may determine the ultimate change in rate of bone turnover after menopause, as well as the development of osteoporosis. Moreover, the enzymes involved in the metabolism of estradiol may form a target for intervention.

17-Hydroxysteroid Dehydrogenases↗

PubMed1998

Adult vs childhood onset GHD: is there a real clinical difference?

As growth hormone (GH) secretion and insulin-like growth factor I (IGF-I) levels decrease with age, it is important to have reliable age- and sex-specific control data for both GH stimulation tests and circulating IGF-I levels. This is particularly true for elderly patients with a history of pituitary disease but with normal production of the anterior pituitary hormones other than GH. The potential impact of these factors on GH deficiency (GHD) has led to a need for the development of reliable, sensitive and specific tests to assess GH reserve. Before starting treatment with recombinant human GH in adults with suspected GHD, it is important to differentiate between adults with childhood onset GHD (CO-GHD) and those with adult onset GHD (AO-GHD). Adults with untreated CO-GHD have significantly lower values for body weight, body mass index, lean body mass and height than those with AO-GHD, while patients with AO-GHD show a more pronounced deviation from normal in psychosocial distress. Following treatment with GH, 12.5 microg/kg/day s.c., patients with AO-GHD showed a decrease in waist/hip ratio and low-density lipoprotein. Quality of life, as measured using the Nottingham Health Profile, changed significantly in both patient groups after 18 months of therapy, though these results were only consistent in subjects with AO-GHD. Improvements were also reported in physical mobility and energy. Side-effects were mainly reported in patients with AO-GHD, and this may have been due to the GH dosage being too high for older patients. In conclusion, CO-GHD in adults appears to be a developmental disorder in patients who have not attained full somatic maturation. The hormonal/metabolic balance and lifestyle of these individuals have adapted to their condition. AO-GHD is a metabolic disorder characterized by a hormonal imbalance affecting the health status, physical condition and quality of life of previously normal adults.

Adult↗

PubMed1997

Differential expression of estrogen receptors alpha and beta mRNA during differentiation of human osteoblast SV-HFO cells.

Estrogens have been shown to be essential for maintaining a sufficiently high bone mineral density and ER alpha expression has been demonstrated in bone cells. Recently, a novel estrogen receptor, estrogen receptor beta (ERbeta) has been identified. Here we demonstrate that also ERbeta is expressed in human osteoblasts, and that ER alpha and ERbeta are differentially expressed during human osteoblast differentiation. ERbeta mRNA expression increased gradually during osteoblast culture, resulting in an average increase of 9.9+/-5.3 fold (mean+/-S.D., n=3) at day 21 (mineralization phase) as compared to day 6 (proliferation phase). In contrast, ER alpha mRNA expression levels increased only slightly until day 10 (2.3+/-1.7 fold) and then remained constant. The observed differential regulation of ER alpha and beta is suggestive for an additional functional role of ERbeta to ER alpha in bone metabolism.

Cell Differentiation↗

PubMed1987

Regulation of the density of spermatogonia in the seminiferous epithelium of the Chinese hamster: I. Undifferentiated spermatogonia.

The topographical arrangement of the clones of A single, A paired, and A aligned (As, Apr, and Aal) spermatogonia on the basement membrane of seminiferous tubules of the Chinese hamster was studied. It was found that at least some of these clones are not distributed at random as clones of similar cell number were often seen in clusters. Areas were found with few or many As spermatogonia. Also, clusters of Apr spermatogonia were found, indicating that in such an area many As spermatogonia more or less synchronously formed Apr spermatogonia. Since clusters of clones of 16 Aal spermatogonia were observed, it can be concluded that these clusters of Apr spermatogonia may proliferate in at least a roughly synchronous way. It was found that over large areas the densities of undifferentiated spermatogonia may be very low or high in comparison to the mean density in the animal. Whether the ratio of self-renewal and differentiation of the stem cells changed locally in response to the high or low density of undifferentiated spermatogonia in particular areas was investigated. No indications for a regulatory mechanism to keep the density of stem cells and/or the density of undifferentiated spermatogonial clones at a certain level could be detected in the normal Chinese hamster. This lack of regulation was at least partly responsible for the widely different numbers of A1 spermatogonia that were formed in the various areas studied in stage IX.

Animals↗

PubMedDate not supplied

Correlations between scale structure and pigmentation in butterfly wings.

We examined the correlation between color and structure of wing scales in the nymphalid butterflies Bicyclus anynana and Heliconius melpomene. All scales in B. anynana are rather similar in comparison to the clear structural differences of differently pigmented scales in H. melpomene. Where scale structural differences in H. melpomene are qualitative, they seem to be quantitative in B. anynana. There is a "gradient" in the density of some structural elements, the cross ribs, in the scales of B. anynana: black, gold, and brown scales show progressively lower cross rib density within an individual. There is, however, high individual variation in the absolute cross rib densities (i.e., scales with a particular color and cross rib density in one individual may have a different color but similar density in another individual). By ectopically inducing color pattern during early pupal development, we examined whether a scale's color and its microstructure could be uncoupled. The effect of these manipulations appears to be different in B. anynana and H. melpomene. In Bicyclus, "black" scales induced by wing damage at an ectopic location normally containing brown scales acquire both an intermediate structure and color between that of brown and normal black scales. In Heliconius, however, intermediate colors or scale structure were never observed, and scales with an altered color (due to damage) always have the same structure as normal scales with that color. The results are discussed on the basis of gene expression patterns, variability in rates of scale development and pigment, and scale sclerotization pathways.

Analysis of Variance↗