Physiological Roles of Cell Growthー or Differentiationーfactors and Their Participations in the Pathologic Changes in the Hereditary Abnormal Models.

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1) Spontaneously hypercholesterolemic (SHC) rats were originally selected based on their high plasma cholesterol levels from sprague-dawley rats and established as a model for hypercholesterolemia. We have found that SHC rat exhibits abnormal bone metabolism characterized by higher excretion of hydroxyproline and calcium into urine, a high level of serum calcium, or a decrease in bone weight and calcium content in the ash. In SHC rats, the rats exhibits abnormalities in endocrine function including hypersecretions of thyroid stimulating hormone and growth hormone preceding the occurrence of renal dysfunction. These abnormalities seems to depend on the cellular component of hormone producing cells in the anterior pituitary gland.2) Hormone producing cells in the anterior pituitary gland are heterogeneous and are thought to be composed of cells in various stages of differentiation. Since some of cells in adult rats are thought to be stem cells, it is possible that activin A may induce di … More fferentiation of proliferation in such stem cells. The mode of action of activin A on the anterior pituitary gland was investigated using primary cultured cells. In the study, folliclestimulating hormone (FSH) secretory activity was stimulated by activin A in a cell density-dependent manner and that the treatment with activin increased the number of FSH cells. Thus, we found that activin A acts on pituitary cells in the same way as a growth- or differentiation promoting factor. We also demonstrated that the capacity of Activin A to release the 2-cell block and stimulate early embryonal development in vitro.3) Prolactin is known to be a hormone carrying luteotropic action in rats and enhances progesterone secretion. We found that transforming growth factor-beta can suppress luteal 20 alpha-hydroxysteroid dehydrogenase activity and that luteotropic action of PRL is at least in part mediated by TGF-beta.4) Electron microscopic studies of glomerular lesions in hereditary nephrotic mice (ICGN strain) and of epiphyseal cartilage of congenital osteochondrodysplasia rat (ocd/ocd) have been done. Less