Abstract.T3 and GH have been implicated in the regulation of mitochondrial biogenesis. Since thyroid hormone promotes the synthesis of growth hormone, its control of human mitochondrial biogenesis could arise through a permissive action on GH biosynthesis. This was studied in hypophysectomized rats treated with T3 and/or human GH by the continuous infusion of hormone for 6 days from mini-infusion pumps implanted sc. Increases in mitochondrial respiration, enzyme activites, and protein synthesis were found in isolated liver mitochondria from rats receiving T3. In contrast, GH alone had no effect, nor did it increase the response to T3. Since it has been argued that mitochondrial biogenesis results from a direct interaction (binding) of GH with mitochondria, GH-specific binding sites were measured with 125I-bGH, a specific somatogenic receptor ligand, in isolated mitochondrial membranes in vitro. In addition, the intracellular endocytic uptake of 125I-bGH injected in vivo was compared in purified subcellular membrane fractions and mitochondria. No evidence in favour of specific GH interaction on mitochondrial membranes was found by either test. It is concluded that T3 exerts a direct, rather than permissive, effect on mitochondrial biogenesis, and that high affinity binding sites for GH are not present in rat liver mitochondria.

1989-07-01·Endocrinology2区 · 医学

Dexamethasone Inhibits Growth Hormone Induction of Insulin-Like Growth Factor-I (IGF-I) Messenger Ribonucleic Acid (mRNA) in Hypophysectomized Rats and Reduces IGF-I mRNA Abundance in the Intact Rat*

2区 · 医学

Article

作者: Jiangming Luo ; Liam J. Murphy

Exogenous glucocorticoids are potent inhibitors of skeletal growth in experimental animals and children. The mechanism whereby glucocorticoids exert this effect is unclear, and circulating somatomedin levels have been reported to be low, normal, or high in this situation. Since recent studies have emphasized the importance of autocrine or paracrine insulin-like growth factor I (IGF-I), we have examined the effects of dexamethasone (DXM) on IGF-I gene expression in the hypophysectomized (hypox) and pituitary intact rat. An increase in IGF-I messenger RNA (mRNA) abundance of approximately 5-, 3-, 2-, and 1.5-fold in the liver, proximal tibia, lung, and kidney, respectively, was seen in hypox rats killed 6 h after injection of human GH (100 micrograms/100 g body wt). As little as 1 micrograms/100 g body wt of DXM administered 3 h before GH injection significantly reduced GH induction of IGF-I mRNA in the liver and the proximal tibia (P less than 0.05 and P less than 0.005, respectively). Higher doses of DXM were required to reduce IGF-I mRNA abundance in the kidney and lung. Of the tissues examined the order of sensitivity to DXM was liver greater than tibia greater than kidney greater than lung. In contrast to the effects of DXM on tissue IGF-I mRNA abundance, an approximately 10-fold higher dose of DXM was required to inhibit the GH-induced rise in serum IGF-I concentration. The effect of DXM on steady state IGF-I mRNA abundance in pituitary-intact rats which were killed 9 h after DXM was also examined. The reduction in IGF-I mRNA abundance required higher doses of DXM (6-360 micrograms/100 g body wt) and was less marked in pituitary-intact rats than in GH-treated hypox rats. In the pituitary-intact rats the order of sensitivity to DXM was tibia greater than liver greater than lung greater than kidney. In acute studies serum IGF-I levels were not decreased by any dose of DXM; rather a significant increase in serum IGF-I was apparent in pituitary intact rats, treated with the lowest and highest doses of DXM. When DXM was administered daily for 6 days to pituitary intact rats, body wt gain and hepatic and tibial IGF-I mRNA abundance were significantly reduced. No significant changes were seen in serum IGF-I concentrations.(ABSTRACT TRUNCATED AT 400 WORDS)

1986-01-01·Endocrinology2区 · 医学

Induction of Growth Hormone (GH) Receptors in Adipocytes of Hypophysectomized Rats by GH*

2区 · 医学

Article

作者: Ingrid Gause ; Staffan Edén

The ability of GH to regulate its own receptor in adipocytes of hormone-substituted hypophysectomized rats was studied. Male rats (130-150 g) were hypophysectomized and substituted with T4 and cortisone. A fixed dose of GH (bovine GH, human GH, or ovine GH), was administered for 5-6 days in three different ways: 1) two injections/day, 2) four injections/day, or 3) by osmotic minipumps. GH binding was measured in cell aliquots using [125I]human GH. In unsubstituted hypophysectomized animals, GH binding was decreased and was approximately 25% of the binding observed in adipocytes of normal rats. With T4 and cortisone replacement, GH binding was partially restored. When GH was administered in four daily injections or via osmotic minipumps, a further increase in GH binding was observed. This increase was observed if the animals were killed up to 6 h but not 12 h after the last GH injection. GH given in two daily injections had no effect on GH binding even when studied at different time periods after the last GH injection. The GH receptor induced by frequent or continuous administration of GH was mainly somatogenic, since an excess of unlabeled ovine PRL inhibited GH binding only to a minor extent. There was no difference in accumulated body weight gain between the GH-treated groups during the treatment period. The results show that GH regulates its own receptor in adipocytes and that the mode of administration of the hormone is of importance for this effect of GH.

100 项与人纤维蛋白原（上海莱士血液制品股份有限公司）相关的药物交易

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