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W G Beamer

Publications and source records attributed to W G Beamer.

At least 109 records · Page 6Linked to original sources
PubMed1986

Ovarian tumors not induced by irradiation and gonadotropins in hypogonadal (hpg) mice.

Hypogonadal (hpg/hpg) mice deficient in gonadotropin-releasing hormone were used to study gonadotropin involvement in ovarian tumorigenesis following gamma irradiation. In the first experiment, 30-day-old hpg/hpg and normal (+/-) littermate mice were irradiated. The same mice were killed 10-15 mo later, and autopsies were performed. Ovaries of irradiated hpg/hpg mice were devoid of oocytes, but retained follicular structures. Neither mesothelial adenomas nor granulosa cell tumors were observed. In contrast, all irradiated +/- mice formed mesothelial adenomas or granulosa cell tumors, or both. Therefore, oocyte death in the absence of gonadotropins did not initiate ovarian tumorigenesis. In the second experiment, irradiated and nonirradiated hpg/hpg and +/- mice were injected 3 times weekly for 180 days with either low or high doses of pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG) in combination. Irradiation reduced ovarian mass and markedly reduced ovarian weight increase in response to exogenous gonadotropins. Follicular dissolution and stromal cell hypertrophy were observed in saline-treated and gonadotropin-treated +/- mice that had been irradiated, and in hpg/hpg mice given the high gonadotropin dose. Mesothelial adenoma formation was observed in 100% of saline-treated, 14% of low dose-treated, and 11% of high dose-treated +/- mice. No mesothelial adenomas developed in any hpg/hpg or nonirradiated +/- mice, despite gonadotropin-induced stromal luteinization. These results indicate that, in the absence of gonadotropins, irradiation leads only to the loss of oocytes. The presence of gonadotropins was necessary to promote follicular dissolution and stromal luteinization, but was insufficient to stimulate mesothelial adenoma formation.

Animals↗
PubMed1986

Gonadotropin uptake in genetic and irradiation models of ovarian tumorigenesis.

Genetic and irradiation models of ovarian tumorigenesis were investigated for evidence that elevated gonadotropins have a role in tumorigenesis. Wx/Wv mice lack oocytes at birth, develop complex mesothelial adenomas by 6 mo, and additional ovarian tumor types later. Uptake of iodinated human chorionic gonadotropin (125I-hCG) was measured in mice aged 1 to 30 mo, and uptake iodinated human follicle-stimulating hormone (125I-hFSH) was measured in mice aged 1 to 12 mo. Gonadotropin uptake by Wx/Wv ovaries in vivo declined quickly and was undetectable by 6 mo. Irradiated ovaries rapidly lost oocytes and follicular structures, formed mesothelial adenomas by 5 mo, and later formed additional types of ovarian tumors. In the irradiation model, 125I-hCG uptake also declined quickly and was undetectable by 3 mo of age. Neither the surface nor the tubular epithelium of the mesothelial adenoma were consistently labeled by 125I-hCG in autoradiography studies with either model. Although these data do not exclude an acute role for gonadotropins in initiation of preneoplastic events, they do indicate that ovarian cells do not require chronic gonadotropin stimulation during subsequent tumorigenesis. These findings are discussed in relation to additional models of ovarian tumorigenesis.

Animals↗
PubMed1986

Gonadotropin, steroid, and thyroid hormone milieu of young SWR mice bearing spontaneous granulosa cell tumors.

Young SWR mice possessing spontaneous ovarian granulosa cell (GC) tumors were examined for evidence of endocrine dysfunction associated with tumorigenesis. Tissue levels of hormones in tumor host and normal control females were measured by radioimmunoassays, ovarian luteinizing hormone (LH) receptors by uptake of 125I-labeled human chorionic gonadotropin (hCG) administered iv, and ovarian 3-beta-hydroxysteroid dehydrogenase (3-beta-OH) activity by histochemical techniques. When data from tumor host mice were compared with control data, hypothalamic gonadotropin releasing hormone content was not significantly different. Pituitary LH and follicle-stimulating hormone (FSH) contents were significantly decreased. Serum FSH, but not LH, levels were significantly reduced. No specific uptake of 125I-labeled hCG by tumor tissue was detected, whereas uptake by nontumorous contralateral ovaries was identified and found to be similar to that of control ovaries. With respect to serum steroids in tumor host mice, progesterone, dihydrotestosterone, and testosterone were significantly reduced, whereas androstenedione, dehydroepiandrosterone, corticosterone, estrone, and estradiol were normal. Frozen sections of tumor tissue failed to show any 3-beta-OH activity, whereas prominent activity was observed in non-tumorous contralateral and control ovaries. Serum thyroxine levels, evaluated because of the known depressive effects of hypothyroidism on reproductive function, were found to be significantly elevated in tumor host mice. The above results suggest that in SWR mice with spontaneous GC tumors, gonadotropins are moderately suppressed; the granulosa tumor cells do not have LH-hCG receptors; steroidogenesis by tumor tissue is reduced, whereas peripheral conversion of adrenal androgen precursors to estrogens is normal; and elevated serum thyroxine levels have a secondary role in established GC tumors.

Animals↗
PubMed1986

Testicular LH receptors and circulating hormone levels in three mouse models for inherited diseases (Tfm/y, lit/lit and hyt/hyt).

In mice with testicular feminization (Tfm/y), the concentration of LH receptors (LH-R) in the testes was greatly elevated, when compared to their normal controls (Ta/y). The administration of hCG caused, 24 hours later, a much greater decrease in the number of testicular LH-R in Tfm/y than in Ta/y mice. However, whereas in Ta/y mice, the decrease in LH-R was accompanied by a greater than 20 fold increase in plasma testosterone (T) levels, the same dose of hCG failed to alter plasma T levels in Tfm/y mice. Tfm/y mice were also characterized by significantly elevated circulating LH, FSH and PRL levels. Administration of hCG decreased testicular LH-R concentration in little (lit/lit) mice, whereas it had no effect in hypothyroid (hyt/hyt) and normal mice. Treatment with hCG elevated plasma T levels in all animals, but this increase was smaller in lit/lit than in Lit/- mice, while being greater in hyt/hyt than in Hyt/- mice. The present results suggest that the Tfm locus in the mouse is involved in the regulation of testicular LH-R. The only effect of GH deficiency on the parameters studied is on hCG-stimulated testicular steroidogenesis. The lack of negative autoregulation of LH-R by hCG in hyt/hyt mice may indicate a more active testicular LH-R metabolism, perhaps as a consequence of the chronic elevation of plasma TSH levels.

Androgen-Insensitivity Syndrome↗
PubMed1985

Spontaneous malignant granulosa cell tumors in ovaries of young SWR mice.

Granulosa cell tumors (GCT) of the ovary appear spontaneously at 4-6 weeks of age in SWR/J and in SWR/Bm inbred strain mice, with a maximum incidence reached by 10 weeks. Cancer was confirmed by metastasis to abdominal organs and by transplantability of primary tumors to histocompatible hosts. Results of genetic crosses showed that GCT appear in SWR X SJL F1 but not in SJL X SWR F1 nor in other F1 females derived from matings of SWR mice with A/HeJ, C57BL/6By, CBA/J, or DBA/2J mice. These findings suggest the maternal transmission of GCT susceptibility. Recombinant inbred strains SWXJ were produced from a progenitor mating of a SWR female to a SJL male. At F20, females in 3 of 14 SWXJ strains developed GCT, with one strain displaying a 5-fold increase in incidence. Embryo transfer studies with SWXJ-6 and -9 mice suggested that maternal transmission was most likely via the fertilized egg rather than through milk or placenta-uterine contact. Analysis of metaphase chromosomes indicated that the modal number in tumors and bone marrow was 40 (2n = 40) with 2 X chromosomes present. Gross chromosomal aberrations were not detected. A working hypothesis proposes that interaction of a unique SWR factor, perhaps cytoplasmic, with nuclear genomic material common to Swiss mouse stocks results in occurrence of GCT in young SWR and SWR-derived mice.

Animals↗
PubMed1984

Adrenal changes in genetically hypothyroid mice.

The adrenocortical X-zone was very poorly developed in young female mice homozygous for the hypothyroid, hyt, mutation, Feeding the mice thyroid powder resulted in the development of an X-zone. This subsequently degenerated in the same way as the X-zone found in the normal litter-mates of the mutants. We suggest that the adrenocortical effects may be due to changes in prolactin stimulation consequent upon the lack of response to thyrotrophin of the mutants.

Adrenal Cortex↗
PubMed1984

Host genetic control of mouse hepatitis virus type-4 (JHM strain) replication. II. The gene locus for susceptibility is linked to the Svp-2 locus on mouse chromosome 7.

Peritoneal macrophages were used to analyze host genetic control of MHV-4 infection in the 14 recombinant-inbred strains between susceptible SWR/J and resistant SJL/J progenitor strains. 4 strains were resistant to MHV-4 infection, while the remaining 10 strains were productively infected. Based upon the strain distribution pattern of susceptibility the gene locus for MHV-4 susceptibility is linked to the Svp-2 locus on the proximal end of mouse chromosome 7. This strain distribution pattern of susceptibility, and hence linkage, was determined to be identical for another MHV strain, MHV-A59. We have suggested that this locus-controlling susceptibility to MHV-4 and MHV-A59 be designated Hv-2.

Animals↗
PubMed1984

"Viable motheaten," a new allele at the motheaten locus. I. Pathology.

A new spontaneous autosomal recessive mutation has recently occurred at the motheaten (me) locus on Chromosome 6 in strain C57BL/6J mice. Homozygotes for the new allele, designated "viable motheaten" (mev), have a mean life span of 61 +/- 2.4 days, compared with only 22 +/- 1.3 days for C57BL/6J-me/me mice. Like the original motheaten mutation, the immediate cause of death in mev/mev mice appears to be severe pneumonitis associated with accumulations of macrophages, granulocytes, and lymphocytes in the lungs. However, because of its longer life span, progression of the disease in mev/mev mice is more amenable to investigation. Eosinophilic crystalline material in alveolar macrophages from mev/mev mice is associated with extravasation of erythrocytes into alveoli. These crystals are morphologically indistinguishable from hematoidin, which results from hemoglobin breakdown following uptake of erythrocytes by macrophages. Severe macrocytic hypochromic anemia with abnormalities in size and shape of erythrocytes develops by 7 weeks. A two-fold increase in peripheral leukocyte count and a five-fold increase in the percentage of neutrophils is seen by 10 weeks. Viable motheaten mice develop focal granulocytic skin lesions by 4 days of age, show depletion of cells from the thymus cortex by 4 weeks, and lack lymphoid follicles in the lymph nodes, spleen, and Peyer's patches. Excessive erythropoiesis and myelopoiesis in the spleen result in marked splenomegaly. Lymph nodes and spleens from mev/mev mice contain increased numbers of plasma cells by 3 weeks; and by 6 weeks, large numbers of atypical plasma cells with Russell bodies are evident. Development of glomerulonephritis by 10 weeks is characterized by granular depositis of immunoglobulin and complement within glomeruli. A twofold increase of blood urea nitrogen levels is present by 15 weeks. Sterility of male mev/mev mice is associated with Leydig cell depletion in the testes, lowered testosterone levels, and impaired spermatogenesis.

Alleles↗
PubMed1983

Etiology of growth hormone deficiency in little, Ames, and Snell dwarf mice.

There are three recessive genes (little, Snell, and Ames) which cause dwarfism and GH deficiency in mice. These genes are nonallelic, and in the case of little mice, GH deficiency is isolated, while Snell and Ames dwarfs have deficiencies of GH as well as other anterior pituitary hormones. Previous reports in which restriction endonuclease analyses were used suggested that the GH genes are grossly intact in each of these types of dwarfs. In this report, ultrastructural studies of the anterior pituitary glands of little mice showed a deficiency or absence of secretory granules within somatotropes, while Snell and Ames dwarf pituitaries lacked identifiable somatotropes. Furthermore, there were deficiencies of GH precursor RNA and mRNA in total RNA from little pituitaries, while GH transcripts appeared to be absent in total RNA from Snell or Ames dwarf pituitaries. Thus, the primary defect in little mice may be in the production of GH transcripts, while GH deficiency in Snell and Ames dwarfs is probably due to defects other than alterations of the GH genes.

Animals↗
PubMed1983

The effect of immunosuppression on streptozotocin-induced diabetes in C57BL/KsJ mice.

The objective of this study was to determine whether mature thymic-derived T-lymphocytes were required for streptozotocin (SZ)-induced insulitis. C57BL/KsJ male mice were immunocrippled by thymectomy at 3 wk of age followed 1 wk later by lethal irradiation (1000 R) and hematopoietic reconstitution with syngeneic bone marrow (pretreated with anti-Thy 1.2 antiserum and complement to eliminate mature T-lymphocytes). As a control for the systemic effects of lethal irradiation itself, thymus-intact males were also irradiated and reconstituted with anti-Thy-1.2-treated marrow cells. This latter treatment resulted in a reconstitution of functional T-lymphocytes. Independent of the presence or absence of functional T-lymphocytes, irradiation extensively damaged the testes and produced at least a 50% reduction in plasma testosterone levels. In such effeminized males, the hyperglycemic response following 6 daily injections of SZ (35 mg/kg) was reduced in comparison to unirradiated males. Pancreatic insulin content was reduced 50% in both thymus-intact and thymectomized groups receiving lethal irradiation and SZ treatment; this correlated with histologic findings of small, beta-cell-depleted islets. Focal leukocytic infiltrates of the exocrine pancreas were induced by the irradiation. Streptozotocin-induced insulitis was also observed regardless of the presence (in thymus-intact mice) or absence (in thymectomized mice) of phytohemagglutinin-responsive T-lymphocytes. Both groups exhibited intact B-lymphocyte function as measured by proliferative responsiveness to lipopolysaccharide. Severe immunosuppression of both T- and B-lymphocyte function was produced by subcutaneous injection of hydrocortisone into thymectomized mice 48 h prior to initiation of SZ treatments. This treatment prevented SZ-induced beta-cell necrosis and eliminated lymphocytic infiltrates in the endocrine and exocrine pancreas. We conclude that functional (mature) T-lymphocytes are not required to mediate the beta cytotoxicity of multiple low doses of SZ in inbred strains in which insulitis accompanies islet destruction. The ability of hydrocortisone to protect beta-cells from the direct cytotoxic action of SZ as well as to eliminate leukocytic infiltration in the pancreas would support the hypothesis that insulitis is a consequence of beta-cell destruction, in this model, rather than its cause. DIABETES 32:148-155, February 1983.

Animals↗
PubMed1982

Defective thyroid ontogenesis in fetal hypothyroid (hyt/hyt) mice.

Thyroid glands of fetal hypothyroid (hyt/hyt) mice were studied to determine the effects of the mutant gene during embryogenesis. Comparisons of mutant and normal thyroids were made with respect to morphology, iodine-concentrating ability, and glandular thyroxine (T4) content at day 18 of gestation. Fetal hyt/hyt thyroid tissue was properly located, but incompletely differentiated. The mutant thyroid was characterized microscopically by small, poorly developed follicles with colloid diminished in PAS-staining properties. The mutant glands' ability to concentrate iodine was found to be only 5--16% of that exhibited by normal glands. When litters contained both mutant and normal off-spring, the differential iodine-concentrating ability allowed fetuses to be separated into two distinct, nonoverlapping populations. The distribution of fetal mice into high or low iodine-concentrating groups agreed closely with predicted frequencies for normal and mutant phenotypes. Thyroid content of T4 in mutant mice was found to be approximately equal to that found in age-matched normal controls. The poorly developed morphology and deficient iodine-concentrating ability of fetal thyroids from day 18 hyt/hyt mice indicated that the mutant gene acts during the ontogeny of this gland. Although such data are not available on human fetuses affected by thyroid dysgenesis, postnatal hyt/hyt mice display characteristics similar to those of infants born with this form of congenital primary hypothyroidism. Thus, elucidation of the site of mutant gene action in the mouse should contribute to our knowledge of disturbed fetal thyroid development and its implications in the adult mammal.

Animals↗
PubMed1982

Analysis of growth hormone genes in mice with genetic defects of growth hormone expression.

Restriction endonuclease analysis of genomic DNA was carried out for three types of dwarf mice (Little, Ames dwarf and Snell dwarf) that have genetic defects in GH expression. We found the GH genes to be present in homozygotes for each mutant allele as well as in their control litter-mates. These three type of dwarf mice may be useful in studying the molecular basis of inherited GH deficiency and as models for analogous genetic disorders of human GH expression.

Alleles↗
PubMed1980

A cytogenetic investigation of inherited true hermaphroditism in BALB/cWt mice.

A predictably high incidence of true hermaphroditism (3%) among fetal BALB/cWt mice provided the opportunity for studying the cause of inherited hermaphroditism. G-banded liver metaphase chromosomes were analyzed from 20 fetal hermaphrodites and from 15 normal female and male littermate controls. All hermaphrodites and seven males were chromosomal mosaics, i.e. XO/XY or XO/XY/XYY. In each mosaic fetus there were more XO than XYY cells. From these findings we hypothesize that BALB/cWt hermaphrodites arise from non-disjunction and probable loss of the Y-chromosome during mitosis. Results from breeding experiments indicated that a defect in the BALB/cWt Y-chromosome per se accounts for its nondisjunction and loss. A significant relationship was found between the amount of ovarian tissue and the percentage of XO cells in mosaic fetuses. If all chromosomally mosaic (XO/XY and XO/XY/XYY) individuals are considered, ovarian tissue was formed if there was 24% or more XO cells in an individual. If only hermaphroditic individuals are considered, ovarian tissue was formed if there were 44% or more XO cells. Finally, we found that the distribution of ovarian and testicular tissue within an ovotestis of BALB/cWt hermaphrodites was not random: ovarian tissue was situated at both ends or only at the cranial end; in only one case was ovarian tissue situated in the center flanked by testicular tissue. We suggest that such nonrandom distribution of ovarian and testicular tissue argues against the hypothesis that the organization of testicular tissue is dependent only on the presence of H-Y antigen.

Animals↗
PubMed1980

Successful treatment of genetically hypophosphatemic mice by 1 alpha-hydroxyvitamin D3 but not 1,25-dihydroxyvitamin D3.

The X-linked hypophosphatemia (Hyp) mutation in the mouse, a model for X-linked familial hypophosphatemic rickets in man, is characterized by defective phosphate transport. The role of vitamin D3 in the defective phosphate transport was investigated in three experiments by treatment of mutant mice with the natural hormonal form of vitamin D3, 1,25-dihydroxyvitamin D3, or its potent synthetic analog, 1 alpha-hydroxyvitamin D3. The results showed that both compounds were able to increase urinary phosphate conservation and improve rachitic bone morphology. Only 1 alpha-hydroxyvitamin D3, however, repaired the critically important hypophosphatemia and significantly increased intestinal transport of phosphate. These results indicate that defective phosphate transport in genetic hypophosphatemia is amenable to effective treatment. We hypothesize that the intestinal phosphate transport system is not genetically deleted but, instead, is unable to respond to 1,25-dihydroxyvitamin D3. Elucidation of the mechanism whereby 1 alpha-hydroxyvitamin D3 is able to stimulate the defective phosphate transport may provide fresh insight into the metabolic basis of the disease.

Animals↗
PubMed1979

The morphology of fetal gonads of spontaneous mouse hermaphrodites.

The gonads of 107 spontaneous, chromosomal mosaic, day-15 fetal hermaphrodites derived from BALB/cWt strain male mice are described and photographs of seven gonads representative of the major types are presented. There were 16 ovaries, 15 testes, and 183 ovotestes. The ovotestes contained on the average more testicular tissue than ovarian, and the ovarian tissue was more frequently located at the gonad poles, particularly the craniad pole. There was no difference between left and right sides with regard to gonad type, but more pure gonads were found on the left than on the right side (21/10), Meioses were observed throughout the ovarian tissue and also in some testicular cords, particularly in the caudad pole of the gonad. Some meiotic figures contained sex vesicles. The significance of these findings is discussed in relation to several aspects of sex determination.

Animals↗