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Biomedical subjects

E M Ritzen

Publications and source records attributed to E M Ritzen.

At least 19 recordsLinked to original sources
PubMed2006

Locally produced estrogen promotes fetal rat metatarsal bone growth; an effect mediated through increased chondrocyte proliferation and decreased apoptosis.

The importance of estrogens for the regulation of longitudinal bone growth is unequivocal. However, any local effect of estrogens in growth plate cartilage has been debated. Recently, several enzymes essential for estrogen synthesis were shown to be expressed in rat growth plate chondrocytes. Local production of 17beta-estradiol (E2) has also been demonstrated in rat costal chondrocytes. We aimed to determine the functional role of locally produced estrogen in growth plate cartilage. The human chondrocyte-like cell line HCS-2/8 was used to study estrogen effects on cell proliferation (3H-labeled thymidine uptake) and apoptosis (cell death detection ELISA kit). Chondrocyte production of E2 was measured by RIA and organ cultures of fetal rat metatarsal bones were used to study the effects of estrogen on longitudinal growth rate. We found that significant amounts of E2 were produced by HCS-2/8 chondrocytes (64.1 +/- 5.3 fmol/3 days/10(6) cells). The aromatase inhibitor letrozole (1 microM) and the pure estrogen receptor antagonist ICI 182,780 (10 microM) inhibited proliferation of HCS-2/8 chondrocytes by 20% (P < 0.01) and almost 50% (P < 0.001), respectively. Treatment with ICI 182,780 (10 microM) increased apoptosis by 228% (P < 0.05). Co-treatment with either caspase-3 or pan-caspase inhibitors completely blocked ICI 182,780-induced apoptosis (P < 0.001 vs ICI 182,780 only). Moreover, both ICI 182,780 (10 microM) and letrozole (1 microM) decreased longitudinal growth of fetal rat metatarsal bones after 7 days of culture (P < 0.01). In conclusion, our data clearly show that chondrocytes endogenously produce E2 and that locally produced estrogen stimulates chondrocyte proliferation and protects from spontaneous apoptosis. In addition, longitudinal growth is promoted by estrogens locally produced within the epiphyseal growth plate.

Animals↗
PubMed2003

Growth retardation induced by dexamethasone is associated with increased apoptosis of the growth plate chondrocytes.

Glucocorticoids cause significant growth retardation in mammals and humans and decreased proliferation of chondrocytes has been considered as the main local mechanism. Death by apoptosis is an important regulator of homeostasis in multicellular organisms. Here we chose to study the role of apoptosis in growth retardation caused by glucocorticoid treatment. We treated 7-week-old male rats with dexamethasone (5 mg/kg/day) for 7 days. Apoptosis was studied in tibiae growth plates by the TUNEL method. Immunoreactivity for parathyroid hormone-related peptide (PTHrP), caspase-3, and the anti-apoptotic proteins Bcl-2 and Bcl-x was also studied. Apoptosis was mainly localized in terminal hypertropic chondrocytes (THCs) in both control and dexamethasone-treated animals. Dexamethasone caused an increase in apoptosis which was fourfold in THCs (2.45+/-0.12 vs 0.62+/-0.09 apoptotic cells/mm growth plate, P<0.001), and 18-fold in proliferative chondrocytes (0.18+/-0.04 vs 0.01+/-0.007 apoptotic cells/mm growth plate, P<0.001). Increased apoptosis after dexamethasone treatment was accompanied by increased immunoreactivity for caspase-3 and decreased immunoreactivity for the anti-apoptotic proteins Bcl-2 and Bcl-x, which further supports our apoptosis results. Dexamethasone also decreased the immunoreactivity for PTHrP, suggesting a role in the mechanism by which glucocorticoids induce apoptosis in the growth plate. We conclude that apoptosis is one mechanism involved in growth retardation induced by glucocorticoids. Premature loss of resting/proliferative chondrocytes by apoptosis could contribute to incomplete catch-up seen after prolonged glucocorticoid treatment.

Animals↗
PubMed2002

Effect of local heating of rat testes after suppression of spermatogenesis by pretreatment with a GnRH agonist and an anti-androgen.

The effects of local heating of rat testes, in which spermatogenesis had been suppressed with injections of a GnRH agonist and an anti-androgen, were examined. Although the detrimental effects of heating were not as marked as those found in the testes of non-injected rats, the testes in which spermatogenesis was suppressed also showed a significant reduction in mass, the number of spermatozoa, tubular diameter and the percentage of normal tubular cross-sections at day 35 after heating. The results indicate that heating has an effect on cells in the testis other than those shown to be most susceptible to heat, namely pachytene spermatocytes and early spermatids, which were absent or markedly reduced in number when spermatogenesis was suppressed. The long-term effects of heating on the above parameters, as reported in a previous study, were also confirmed. However, in testes in which spermatogenesis was suppressed at the time of heating, there appeared to be no or a reduced long-term impairment of spermatogenesis, as determined by testis mass, the percentage of qualitatively normal tubules and epididymal sperm counts.

Analysis of Variance↗
PubMed2001

Reduction of long-term effects of local heating of the testis by treatment of rats with a GnRH agonist and an anti-androgen.

Heating the testes of anaesthetized adult rats to 43 degrees C for 30 min in a waterbath was followed by a large decrease in testis and epididymis mass and number of spermatozoa 35 days later. These parameters had recovered to some extent, but not completely, by days 70 and 97 after heating, but had decreased again in rats examined on day 182. There were no consistent effects of heating on androgen status, as determined by the concentrations of testosterone in blood and testis fluids, or by seminal vesicle mass, and interstitial fluid volume was increased in the heated testes. Treatment of rats with an implant of a GnRH agonist and daily injections of an anti-androgen for 14 days (sufficient in itself to cause large temporary decreases in tissue mass, number of spermatozoa and androgen status) did not reduce the initial decrease in testis mass or number of spermatozoa seen after heating, but reduced the later decreases in mass and number of spermatozoa significantly. These findings indicate that, as well as causing damage to spermatocytes and spermatids, as previously reported, heating also reduces the ability of spermatogonia to repopulate the seminiferous tubules at longer intervals after heating. Furthermore, it appears that this effect on the spermatogonia can be reduced by treating the animals with a GnRH agonist and anti-androgen, a treatment similar to that shown by other authors to improve recovery of the testis from irradiation or drug treatment.

Androgen Antagonists↗
PubMed1999

Disproportional body growth in female estrogen receptor-alpha-inactivated mice.

Estrogens play an important role in the regulation of longitudinal bone growth in man, as demonstrated by recent descriptions of individuals with estrogen insensitivity or aromatase deficiency. Two estrogen receptors, ERalpha and ERbeta, have been cloned. The aim of the present study was to investigate the function of ERalpha in the regulation of body growth and skeletal growth. Adult female mice with inactivated ERalpha (ERalpha-/-) demonstrated an increased body weight compared with wild-type mice (114% of control). However, the length of the appendicular skeleton was decreased in adult ERalpha-/- mice (femur 93% of control). In contrast, the axial skeleton was normal (crown-rump length 98% of control). The decreased growth of the appendicular skeleton was associated with decreased serum levels of IGF-I (77% of control), indicating that the GH/IGF-I axis may be involved in the decreased longitudinal bone growth seen in female ERalpha-/- mice.

Animals↗
PubMed1998

Reduction in fluid secretion by rat testis by drugs that block potassium channels.

The effect of two class III antiarrhythmic drugs (Almokalant, Astra-Hässle and Dofetilide, Pfizer) on fluid secretion by rat testes has been examined. Both drugs reduced fluid secretion, whether this was measured by the amount of rete testis fluid that could be collected 22 h after unilateral efferent duct ligation, or by the difference in mass between the ligated and unligated testes, or by the difference in amount of supernatant fluid after the parenchyma of the ligated and unligated testes had been dispersed and centrifuged. The secretion of potassium, calculated from the amount of potassium in the supernatant fluids from the ligated and unligated testes was also reduced by the drugs, whereas the secretion of androgen-binding protein and inositol was unaffected. The concentration of potassium in the secreted fluid, calculated from the amount and composition of the supernatant fluids, was not affected by treatment of the rats with Almokalant, but was increased in rats treated with Dofetilide and, in these, the concentration of sodium was reduced and that of magnesium and inositol was increased and the concentration of total protein was unaffected. The concentration of androgen-binding protein in secreted fluid was increased in rats treated with Almokalant, while the concentration of testosterone was unaffected. Histological examination of testes from treated rats revealed phagocytosis of stage 19 spermatids in tubules at stages VIII-IX after 2 days, at stages IX-XI after 4 days and at stages VIII-XIV after 7 days, apparently owing to an effect on spermiation. It appears that these drugs interfere with potassium-mediated fluid secretion by the testis, leading to the other changes seen.

Analysis of Variance↗
PubMed1986

Changes in germ cell adenylate cyclase and protein carboxyl methylase activities in rat testicular tissue during bilateral cryptorchidism and after orchidopexy.

Soluble Mn2+-dependent adenylate cyclase and protein carboxyl methylase are two enzymes that are primarily localized in haploid germ cels of rat testicular tissue, and both enzymes exhibit an increase in activity in association with sexual maturation. Experimental cryptorchidism (surgery at 17 days of age) in immature rats prevented the age-dependent increase in the activity of these two testicular enzymes. After orchidopexy at 34 days of age the activities of these two enzymes increased to normal control values in association with testicular growth. These observations show that biochemical markers such as soluble Mn2+-dependent adenylate cyclase and protein carboxyl methylase can be used to follow germ cell differentiation.

Adenylyl Cyclases↗
PubMed1985

Stage-specific inhibition of interstitial cell testosterone secretion by rat seminiferous tubules in vitro.

The stage-specific influence of the secretions from rat seminiferous tubules on the LH-stimulated testosterone production by rat Leydig cells in vitro was studied. The spent media from incubated seminiferous tubules (SMST) from stages VII-VIII of the seminiferous epithelial cycle caused about 50% inhibition of the LH-dependent testosterone production by a crude preparation of rat interstitial cells. The SMST from other stages had no effect on testosterone production. Mixed tubules of unidentified stages gave an intermediate response. When SMST from ten different stages of the seminiferous wave were compared, the most pronounced inhibitory activity was found in stages VI and VIII-XI, while SMST from stages I, VII and XIII-XIV had no inhibitory effects on interstitial cell testosterone production. No stimulation was found in this system. Prolonged incubation of the interstitial cells with SMST from stages VIII-XI resulted in loss of inhibitory activity after 12 h of incubation. Maximum inhibitory activity was noted after 3 h of incubation. The inhibitory activity of the SMST from stages VIII-XI was retained after prolonged dialysis, and was unchanged after heating the medium at 60 degrees C for 1 h. The activity did not seem to be due to the presence of proteolytic enzymes, since it was not influenced by addition of protease inhibitors. SMST from stages VIII-XI had no effect on the metabolism of [3H]testosterone added to the interstitial cell preparations. No inhibitory effect was observed when Leydig cells were incubated with dibutyryl cAMP instead of LH, suggesting an early influence on the LH-receptor-adenylate cyclase chain of events.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1983

Dyggve-Melchior-Clausen dysplasia. Morphological and biochemical findings in cartilage growth zones.

The results of light and electron microscopic examination and of biochemical proteoglycan studies of costochondral and iliac crest biopsies from a recently diagnosed case of Dyggve-Melchior-Clausen dysplasia are reported. At light microscopy of resting cartilage large lacunae containing clusters of five or more chondrocytes were seen in some areas. In the hyaline cartilage there were scattered fibrous foci but no mineralized areas. Electron microscopy revealed chondrocytes containing widened cisternae of rough endoplasmic reticulum and vesicles coated with a smooth single-layered membrane. The content of the cisternae and of the vesicles was amorphous. Throughout the cartilage a considerable proportion of the chondrocytes displayed more or less pronounced necrobiotic changes. The biochemical analysis showed an increased amount of glucosaminoglycans in the cartilage and indicated that the ability of proteoglycan monomers to reaggregate to hyaluronic acid chains was decreased. Our findings support the suggestion that Dyggve-Melchior-Clausen dysplasia is due to a disturbance in proteoglycan metabolism.

Cartilage↗
PubMed1982

Stage-dependent secretion of ABP by rat seminiferous tubules.

The secretion rate of the Sertoli-cell-specific androgen-binding protein (ABP), has been studied in isolated rate seminiferous tubules, where the stages of the spermatogenic cycle have been identified by a transillumination method. The secretion of ABP was highest in stages VII-XII, as determined by steady-state polyacrylamide-gel electrophoresis as well as by radioimmunoassay. More specifically, when the sensitive RIA technique permitted the assay of ABP secretion from a total amount of 10-30 mm of isolated tubules, it was found that maximal ABP secretion occurred at stages VIII-XI and minimal at stages IV-V. The present results show that the secretory activity of the Sertoli cells (ABP) is influenced by the type of germ cell at each cell association. It is postulated that the variation is Sertoli-cell secretory activity is of importance for the normal maintenance of spermatogenesis.

Androgen-Binding Protein↗
PubMed1976

Hormones and hormonal target cells in the testis.

Studies over the last few years have greatly increased our knowledge about target cells for sex hormones and gonadotropins in the testis. A diagram illustrating our present state of knowledge is given in Fig. 1. LH is the principle stimulus of testosterone secretion by the Leydig cells. Direct effects of estrogens and androgens on these cells might modulate the response to LH. Androgens are apparently influencing the differentiation and the contractility of peritubular cells. FSH is the principle stimulus for Sertoli cell secretory function before puberty, although androgens are acting synergistically with FSH. After puberty, androgens alone are capable of maintaining on optimal secretory function of the Sertoli cells. In addition to normal secretory activity of the Sertoli cells, direct stimulation of the germ cells by androgens is needed in order maintain spermatogenesis.

Age Factors↗