Ruth Silberberg

STEROID HORMONES AND BONE

Publisher Summary Many of the steroid hormones influence skeletal growth, development, and ageing; sex steroids in addition regulate the development of osseous structures representing secondary sex characters, such as horns and antlers. In birds, these steroids also control skeletal changes that are incidental to egg-laying, namely, medullary bone formation. The effects of steroid hormones on bone are thus manifold, and even though some of the end results might appear similar, they can be brought about by different mechanisms. Direct and circumstantial evidence strongly indicates that steroid hormones might act on the skeleton directly without mediation of other endocrine glands. Only a limited number of investigations have been carried out, and so far little information has been forthcoming concerning the skeletal effects of progesterone, of desoxycorticosterone and related substances, and even of the glucocorticoids. Of the steroid hormones tested, only the androgenic 17-ketosteroids in small doses have been shown to increase linear growth; this effect seen only in individuals, whose body growth is retarded because of certain endocrine deficiencies, is related to the increased N retention caused by the 17-ketosteroids.Publisher Summary Many of the steroid hormones influence skeletal growth, development, and ageing; sex steroids in addition regulate the development of osseous structures representing secondary sex characters, such as horns and antlers. In birds, these steroids also control skeletal changes that are incidental to egg-laying, namely, medullary bone formation. The effects of steroid hormones on bone are thus manifold, and even though some of the end results might appear similar, they can be brought about by different mechanisms. Direct and circumstantial evidence strongly indicates that steroid hormones might act on the skeleton directly without mediation of other endocrine glands. Only a limited number of investigations have been carried out, and so far little information has been forthcoming concerning the skeletal effects of progesterone, of desoxycorticosterone and related substances, and even of the glucocorticoids. Of the steroid hormones tested, only the androgenic 17-ketosteroids in small doses have been shown to increase linear growth; this effect seen only in individuals, whose body growth is retarded because of certain endocrine deficiencies, is related to the increased N retention caused by the 17-ketosteroids.

Endochondral Ossification in Achondroplastic Dwarfism

Abstract The literature concerning endochondral histopathology in the chondrodystrophies is misleading because the true heterogeneity of this group of disorders was not recognized until relatively ...

Early Onset of Disk Degeneration and Spondylosis in Sand Rats (Psammomys Obesus)

The sand rat is a desert animal which feeds mainly on salt bush, a shrub with a high salt content in its leaves. Sand rats have been used for the study of renal function, and since they may develop diabetes if kept on a laboratory diet without a supplement of salt bush, they have been used for investigation of diabetes-related disorders as well. Older diabetic and non-diabetics and rats are prone to develop severe degeneration of the intervertebral disks, disk herniation, and subsequent hyperostotic spondylosis. This report is concerned with the relation of these processes to aging. The vertebral columns of 25 sand rats which were fed a standard laboratory diet and a supplement of salt bush ad libitum were examined. The sand rats ranged from 12 to 18 months of age. The vertebral columns were dissected, prepared for microscopic examination, and the findings were compared with those obtained previously in sand rats from 1 ½ to 2 ½ years of age. Both disk degeneration and spondylosis were comparable in course and frequency to the changes found in the older sand rats. It was concluded that factors other than age are involved in the pathogenesis of disk degeneration in the sand rat.

Articular Aging and Osteoarthrosis in Dwarf Mice

In aging hypopituitary dwarf mice (dwdw), articular chondrocytes are poorly supplied with organelles; aggregation of collagen in the cartilaginous matrix is decreased, and aging of the articular cartilage is retarded as compared to non-dwarf mice (Dwdw or DwDw) of the same strain. Osteoarthrosis developing in 58% of male and in 22 % of female non-dwarfs was not observed in dwarfs regardless of sex. The unusually long life span of dwarf mice suggests that in hypopituitarism aging of non-skeletal tissues is likewise retarded.

Chondro-osseous pathology in the chondrodystrophies.

The majority of chondrodystrophies are associated with distinct abnormalities in chondro-osseous histopathology. In some disorders, the pathological abnormalities are characteristic and can be used as diagnostic criteria, in other instances the morphological abnormalities are not specific, and in still others, no abnormality in chondro-osseous morphology is present. In this paper, the chondro-osseous histopathology and ultrastructure of a number of chondrodystrophies are reviewed to illustrate the different pathogenetic mechanisms involved in each of these disorders.

Aging Changes in Intervertebral Discs and Spondylosis in Chinese Hamsters

Vertebrae and intervertebral discs of Chinese hamsters, a species of rodents that develop spontaneous diabetes, were investigated for age-linked changes and for the occurrence of spondylosis. Aging changes in the intervertebral discs were similar in diabetic and nondiabetic animals. The incidence of spondylosis was significantly increased and its onset was accelerated in the diabetic animals. The mechanisms operative in the pathogenesis of the lesions and their relation to the human disease are discussed.

Histologic and Morphometric Observations on Vertebral Bone of Aging Sand Rats

The trabecular bone of the vertebrae of 30 male and 30 female sand rats (Psammomys obesus) aged 13 to 33 months was examined hlstologlcally and morphometrlcally. The usual age-linked decline of bone mass failed to occur In females and was statistically not significant In males. A few changes with age were noted at the cellular level. Sex differences were statistically significant only In animals living Into the third year of life, males having a smaller bone mass than females. This abnormality of the vertebral sponglosa Is attributed to pathologic local stresses caused by the numerous Instances of disc degeneration and hernlatlon. Differences In size, location, and age of the hernlatlons are thought to account for the wide fluctuations In the Individual bone parameters examined. Whereas the spine of the sand rat provides an excellent model for the study of spondylosis, It Is unsulted as a model for age-linked osteoporosis.

Diastropic Dwarfism: a Histochemical and Ultrastructural Study of the Endochondral Growth Plate

Summary: Chondro-osseous tissue from five patients with diastropic dwarfism was studied by histologie, histochcmical, and electron microscopic methods. The major abnormalities observed were: 1) irregular distribution of chondrocytes undergoing degeneration in the resting cartilage; 2) abnormal distribution of collagen in the resting cartilage; 3) a spectrum of fibrous matrix lesions in the resting cartilage which ranged from focal areas of aggregated collagen fibrils to large cystic lesions in which intracartilagenous ossification occurred; and 4) shortened, irregular cellular columns within the growth plate which were occasionally disrupted by matrix lesions extending from the resting cartilage. These alterations in chondro-osseous morphology have not been observed in any of the other skeletal dysplasias examined to date and appear to be pathognomonic for this disorder.Speculation: The basic abnormality in diastropic dwarfism may be a metabolic abnormality in the chondrocyte which predisposes it to cell death or a processing defect in its synthesis of either collagen or proteoglycan. An enzyme deficiency could produce either type of defect and would be consistent with the autosomal recessive inheritance of this disorder.

ULTRASTRUCTURE OF ARTICULAR CARTILAGE OF MICE TREATED WITH SOMATOTROPHIN.

Administration of somatotropic hormone to newborn or weanling mice of strain C57BL Jax6 for one, two, or four weeks accelerated articular growth and development. The organelles were increased in number and the appearance of granular endoplasmic reticulum, Golgi vacuoles, multivesicular bodies, and glycogen was hastened. Toward the end of the developmental cycle, the chondrocytes swelled excessively and their plasmalemma ruptured without evidence of vascular erosion. After four weeks of treatment, there was premature breakdown of chondrocytes, their place being taken by fibrillar microscars. In the matrix, development of fibers was accentuated. The intensification of fibrillarity was followed by disorientation of the superficial collagen fibers with fraying of the articular covering. The functional significance of these findings, as well as their relation to aging changes in cartilage, is discussed.

Enzyme Studies in the Articular Cartilage of Diabetic Rats and of Rats Bearing Transplanted Pancreatic Islets

The articular cartilage of normal rats, of rats made diabetic with streptozotocin, and of rats made diabetic with streptozotocin and subsequently transplanted with isologous pancreatic islets was examined for the activities of enzymes engaged in the synthesis and degradation of glycosaminoglycans (mucopolysaccharides). The activities assayed were those of the degrading enzymes B-glucuronidase, B-acetyglucosaminidase, B-acetylgalactos-aminidase, B-galactosidase, and those active in synthesis: uridine-diphosphate dehydrogenase, ghicose-6-phosphate dehyrogenase, and phosphofructokinase. In the diabetic animals all enzyme activities were increased, those of the degrading enzymes more than those of the others. Implantation of pancreatic islets reversed the changes produced by diabetes, enzyme activities returning to near-normal levels.