Walter K. Morishige

Na+ pump activity and nuclear T3 receptors in tissues of genetically obese ( ob ob ) mice

A dramatic reduction in ouabain-sensitive tissue respiration of obese mouse muscle and liver was observed, suggesting that Na+-transport-dependent calorigenesis is impaired in these animals. Additionally, a significantly depressed nuclear triiodothyronine binding capacity in liver and lung tissue was exhibited by obese mice. These data support the suggestion that the hypometabolism and hypothermia of the genetically obese mouse is a result of reduced Na+-pump-related thermogenesis; and further, provides evidence that this may be the consequence of reduced nuclear binding of triiodothyronine.

The Effect of Corticosterone on the Growth of Perinatal Rat Lung Fibroblasts in Culture: Modulation by the Extracellular Matrix

Third passage lung fibroblasts from rat pups between the ages of fetal day 17 and postnatal day 15 were allowed to attach onto either tissue culture plastic or an endothelial cell‐derived matrix, and were then exposed to different concentrations of corticosterone in culture medium containing 1% charcoal‐stripped serum. The effect of the hormone on growth of these cells was assessed after 48 hours of exposure by radiothymidine incorporation into DNA. Lung fibroblasts on plastic responded to the hormone in an age‐dependent manner; thus, cells which were obtained during late gestation (days 19–21) and after the third day of extrauterine life were consistently growth‐inhibited by corticosterone, whereas those which were obtained from fetal donors prior to day 19 and from neonatal donors (days 0–3 after birth) were stimulated to grow in response to the hormone. On the other hand, cells that were plated onto an endothelial cell‐derived matrix showed a different age‐related response to the hormone. Thus, lung fibroblasts from all fetal donors and from postnatal donors up until 4–5 days of age were stimulated to grow in response to corticosterone. This modulatory effect of the matrix on the fibroblast response to corticosterone was also seen in early passage fibroblasts. In an attempt to identify the modulatory agent(s) in the extracellular matrix, fibroblasts from day 19 fetal rat lung were challenged with corticosterone in the presence of laminin, fibronectin, type IV collagen, type I collagen, heparin, or chondroitin sulfate. None of these agents exerted a modulatory effect resembling that seen with the extracellular matrix. These results suggest the existence during lung development of a fibroblast‐endothelial interaction, the nature of which remains to be elucidated, which may serve to modify the effects of circulating hormones.

CHAPTER 33 – Endocrine Metabolism IV: Thyroid Gland

The thyroid gland consists of two lobes connected by an isthmus and is positioned on the ventral surface of the trachea just below the larynx. It receives adrenergic fibers from the cervical ganglion and cholinergic fibers from the vagus, and is profusely vascularized by the superior and inferior thyroid arteries. Histologically, thyroid tissue is composed of numerous follicles lined by a single layer of epithelial cells around a lumen filled with proteinaceous material called colloid. The follicle cells, called thyrocytes, produce the thyroid hormones and are derived from the entodermal pharynx. Two substrates are required in the synthesis of thyroid hormones. The intrinsic substrate is thyroglobulin (Tg), a homodimeric glycoprotein synthesized in the rough endoplasmic reticulum of the thyrocytes and secreted into the follicular lumen by exocytosis. The extrinsic substrate is elemental iodine, present in food as inorganic iodide. Iodide is readily absorbed via the small intestine, and it is almost entirely removed from the general circulation by the thyroid and kidney. Iodide, which is taken up by salivary and gastric glands is secreted in salivary and gastric fluids, and is returned to the plasma iodide pool by intestinal reabsorption. A small amount of iodide is taken up by the lactating mammary gland and appears in milk. The thyroid gland autoregulates its iodine supply by an internal feedback mechanism that controls the intraglandular handling of iodide and the thyroid response to TSH.

Lung-Derived Growth Factors: Ontogenic Shift in Parahormone Secretion in the Perinatal Rat Lung

Primary cultures of perinatal rat fibroblasts were found to produce at least three mitogenic activities which exhibited specificity for distinct cell types. One activity, lung growth factor(LGF), was a potent mitogen for chick embryonal fibroblasts, which also stimulated fetal rat lung fibroblasts to undergo DNA synthesis, provided that these cells were first exposed to a “competence” factor such as fibroblast growth factor or platelet‐derived growth factor. Although LGF was active in the somatomedin‐C (SmC) radioimmunoassay and resembled buffalo rat liver multiplication‐stimulating activity (brlMSA) in molecular size, it appears to consist of a component that is neither SmC nor brlMSA. The second activity produced by perinatal rat lung cultures, pneumocyte‐stimulating activity (PSA), stimulated mitosis in type II pneumocytes of postnatal rats, and was found to have physical attributes that are distinct from those of the other known pneumocyte‐influencing factors. The third activity is a non‐dialyzable substance which complements the mitogenic action of LGF on fetal lung fibroblasts, and appears to be a “competence” activity. An examination of the production of LGF and PSA by rat lung fibroblasts taken at various intervals of development revealed that fetal lung fibroblasts produce maximal levels of LGF but low levels of PSA, whereas, in neonatal lung fibroblasts, the situation is reversed. This ontogenic shift in the type of parahormone produced by the developing perinatal rat lung may be an important regulatory event in postnatal lung morphogenesis in this species.