Increased plasma corticosterone levels in bovine growth hormone (bGH) transgenic mice: Effects of ACTH, GH and IGF-I onin vitro adrenal corticosterone production

Abstract

Previous work from our laboratory provided evidence for increased plasma corticosterone levels in mice transgenic for human and bovine growth hormone (GH). Corticosterone was elevated in both sexes, under both basal and ether-induced stress conditions. The objectives of the present study were to investigate the in vitro adrenal sensitivity to ACTH, GH and/or IGF-I in normal and bGH transgenic mice, to examine plasma corticosterone levels at different times of the day, and to determine plasma levels of ACTH in these animals. For the measurement of plasma corticosterone and ACTH levels, transgenic and normal siblings were housed 2 per cage and decapitated simultaneously within 20 seconds of the first disturbance of the cage. The corticosterone production by in vitro adrenal incubations did not differ between adrenals from normal and transgenic mice at the basal level or in the presence of different doses of ACTH. Growth hormone or IGF-I did not have any effect on corticosterone production in vitro when given alone, and did not modify the effects of ACTH on the accumulation of corticosterone production in vitro when alone, and did not modify the effects of ACTH on the accumulation of corticosterone in the media. Plasma corticosterone concentrations were higher in transgenic than in normal animals in both morning and evening. Plasma concentrations of ACTH in animals killed in the morning were sharply increased in transgenic males as compared with their normal siblings. The results indicate that increased circulating levels of corticosterone in transgenic mice are not due to a potentiation of ACTH actions by GH or IGF-I, but rather to a chronic increase in plasma ACTH levels. The increase in ACTH is presumably a reflection of GH actions in the hypothalamic-pituitary system.

ACTH is a potent regulator of gene expression in human adrenal cells

“…Although previous studies has identified some ACTH responsive genes that are involved with the steroidogenic and growth related effects of ACTH (Cecim et al 1996; Gaillard et al 2000; Le Roy et al 2000; Markowska et al 1993; Neri et al 1991; Phillips et al 1996; Simmonds et al 2001), there is a lack of knowledge regarding the global actions of ACTH on gene expression. Given the critical role of ACTH in adrenal development, steroidogenesis and disease, it is appropriate to further define the detailed effects of ACTH on human adrenal cell gene expression.…”

Lack of contribution of 11βHSD1 and glucocorticoid action to reduced muscle mass associated with reduced growth hormone action

“…It has been reported that plasma corticosterone levels in bGH mice were increased as a consequence of increased adrenocorticotropic hormone (ACTH) secretion [21,22]. IGF-I mRNA levels were increased in skeletal muscle of bGH mice.…”

Modifier Selection by Transgenes: The Case of Growth Hormone Transgenesis and Hyperactive Circling Mice

“…DA and NE show gender-specific alterations and rapid age-related declines (Steger et al 1991(Steger et al , 1993Bartke et al 1994Bartke et al , 1999Cecim et al 1996). Modulators of locomotion and/or circling include adenosine, ACh, 5-HT, thyroid stimulating hormone, SRIF, orexins, glutamate and especially DA (Blackburn et al 1984;Koshikawa et al 1990;Fitzgerald et al 1993;Fedrowitz et al 2000;Nakamura et al 2000;Kincaid 2001;Hathway et al 2003;Isaac and Berridge 2003).…”