The physiological role of IGF-II remains unclear but there is evidence for a role in postnatal growth, the growth of the thymus and bone homeostasis. Glucocorticoids have many effects that are opposite to the effects of IGF-II such as growth retardation, osteoporosis and thymic involution. We therefore wondered whether IGF-II overexpression in transgenic mice might counteract some of the growth inhibitory effects of the glucocorticoid, dexamethasone (DXM).In a dose-finding study in normal mice, 20 µg DXM/ day caused a significant growth delay. The various organs had a different susceptibility to the growth inhibitory effects of DXM. Most affected were thymus and spleen, followed by liver, skeletal muscle and lumbar vertebrae. The weights of the kidney, tibia, and humerus were not significantly diminished.In a second experiment, the effects of DXM in normal and IGF-II-transgenic animals were compared. The IGF-II serum levels in the transgenic animals were more than 40-fold increased compared with control mice and were decreased by 35% in the DXM-treated group. IGF-I serum levels were identical in both mouse strains and rose slightly after DXM administration in controls. Transgenic mice had higher levels of IGF binding protein species of apparent molecular masses of 41·5 kDa, 30 kDa, and 26·5 kDa. DXM reduced the 24 kDa band in both mice strains. In addition it reduced the bands at 38·5 kDa and 26·5 kDa but only in the transgenic animals.The effect of DXM on body growth was similar in normal and IGF-II-transgenic mice. The weight reduction of the various organs caused by DXM was similar in both types of mice except for the skeleton. The weight of the tibia and the humerus were significantly higher in the DXM-treated transgenic mice.In conclusion, we speculate that overexpression of IGF-II in mice partially protects bone from the osteopenic effects of glucocorticoids.

The ability to adjust skin darkness to the background is a common phenomenon in fish. The hormone a-melanophore stimulating hormone (aMSH) enhances skin darkening. In Mozambique tilapia, Oreochromis mossambicus L., aMSH acts as a corticotropic hormone during adaptation to water with a low pH, in addition to its role in skin colouration. In the current study, we investigated the responses of this fish to these two environmental challenges when it is exposed to both simultaneously. The skin darkening of tilapia on a black background and the lightening on grey and white backgrounds is compromised in water with a low pH, indicating that the two vastly different processes both rely on aMSH -regulatory mechanisms.If the water is acidified after 25 days of undisturbed background adaptation, fish showed a transient pigmentation change but recovered after two days and continued the adaptation of their skin darkness to match the background. Black backgrounds are experienced by tilapia as more stressful than grey or white backgrounds both in neutral and in low pH water. A decrease of water pH from 7.8 to 4.5 applied over a twoday period was not experienced as stressful when combined with background adaptation, based on unchanged plasma pH and plasma aMSH and Na levels. However, when water pH was lowered after 25 days of undisturbed background adaptation, particularly aMSH levels increased chronically. In these fish, plasma pH and Na levels had decreased, indicating a reduced capacity to maintain ion-homeostasis, implicating that the fish indeed experience stress. We conclude that simultaneous exposure to these two types of stressor has a lower impact on the physiology of tilapia than subsequent exposure to the stressors. * Cover Letter

Supraphysiological doses of glucocorticoids cause growth retardation in both animals and humans. Many studies have addressed the interaction of glucocorticoids with the GH/IGF system, but little is known about the effect of glucocorticoids on T(4)-stimulated growth. The Snell dwarf mouse is deficient in GH, thyroid-stimulating hormone, and prolactin and therefore allows the study of the effect of glucocorticoids on the growth induced by GH and T(4) without their mutual interaction. Four weeks of treatment with T(4) (1 micro g/d) or human GH (50 mU/d) equally increased nose-tail length (3.1 +/- 0.1 cm and 3.0 +/- 0.2 cm, respectively). Dexamethasone (DXM) had much less impact on T(4)-stimulated growth than on GH-induced growth (T(4) + DXM: 2.4 +/- 0.1 cm vs. GH+ DXM: 1.4 +/- 0.1 cm). Similar data were obtained for body weight gain. T4 and GH had a different effect on the weight of various organs: GH caused a higher increase in liver and lumbar vertebrae weight, and T(4) was a better stimulator for kidney (P < 0.05), thymus, and spleen growth. Remarkably, T(4)-stimulated growth of the organs was less affected by DXM than GH-induced organ growth. GH even potentiated the growth inhibition by DXM in the thymus and tibia. In conclusion, T(4)-stimulated growth in Snell dwarf mice is less affected by DXM than growth stimulated by GH

Growth retardation is a serious side effect of long-term glucocorticoid (GC) treatment. In order to prevent or diminish this deleterious effect, a combination therapy including growth hormone (GH), a stimulator of bone growth, is often recommended. Parathyroid hormone (PTH) and thyroid hormone (T(4)) are important hormonal regulators of bone growth, and might also be helpful anabolic agents for counteracting the negative effects of GCs. Therefore, we studied the interaction of GCs in combination with a single dose of either PTH or T(4) on GC-induced growth retardation. Dexamethasone (Dex) treatment of mice for four weeks induced a significant growth inhibition of body length and weight and weights of several organs. PTH or T(4) alone did not affect the normal growth pattern. However, T(4) could partially restore the Dex-induced growth inhibition, whereas PTH could not. Although PTH did not affect total body growth, it did affect the height of the proliferative zone, which could be counteracted by Dex. This contrasts with T(4) treatment alone or in combination with Dex, which both resulted in a disturbed morphology of the growth plate. IGF-I mRNA, one of the mediators of longitudinal bone growth, was present in proliferative and hypertrophic chondrocytes. However, its expression was not affected by any of the treatments. In conclusion, T(4) but not PTH can partially counteract the effects of Dex on general body growth, with possible implications for future treatments of GC-induced growth retardation. Additionally, both T(4) and PTH, alone or in combination with Dex, have differential effects on the morphology of the growth plate.