The growth hormone axis, feeding, and central allocative regulation: lessons from giant transgenic growth hormone mice

Abstract

Lifetime consumption rates of male transgenic growth hormone (GH) mice and normal controls were measured on either a 38% protein diet (HP), the standard rodent diet (STD) (23.5% protein), or the standard diet supplemented with a free choice of sucrose (CARB). On STD, daily intake of normal mice increased little at sizes greater than 20 g, but larger transgenic mice ate progressively more. Both kinds of mice showed declining daily mass-specific consumption with increasing age. Transgenic mice consistently ate 13.3% less food than normal mice on a mass-specific basis across all ages. On the self-selective CARB diet, normal mice exhibited increasing age-specific daily consumption, whereas transgenic mice exhibited a trend towards age-related decline in mass-specific feeding that proved significant on the basis of body mass. Transgenic mice ingested more sucrose than standard chow and this did not vary with age. In contrast, normal mice ate less sucrose than chow and chose a declining proportion of sucrose with age. Transgenic and normal mice showed a unitary relationship of daily intake of HP in relation to body mass, resulting in constant mass-specific feeding across all ages. Transgenic GH animals, including livestock, show numerous defects that we have attributed to relative energetic stress associated with excessive allocation to lean growth. This is exacerbated by failure to offset increased demands of growth by increasing mass-specific feeding. Results presented here document altered feeding regulation in transgenic GH mice and suggest underlying mechanisms.Résumé : Les taux de consommation durant toute la vie ont été mesurés chez des mâles de souris à hormone de croissance (GH) transgénique soumises à un régime alimentaire contenant 38% de protéines (HP), à un régime standard de rongeur (STD) contenant 23,5% de protéines ou à un régime standard additionné de sucroses au choix (CARB). Au régime STD, la consommation chez les souris normales augmente peu aux tailles supérieures à 20 g, mais les souris transgéniques plus grosses augmentent progressivement leur consommation de nourriture. Les souris des deux types diminuent leur consommation quotidienne de nourriture en fonction de leur masse à mesure qu'elles vieillissent. Les souris transgéniques mangent 13,3% moins de nourriture par unité de masse à tout âge. Au régime CARB, les souris normales augmentent leur consommation quotidienne en fonction de leur âge, alors qu'en vieillissant, les souris transgéniques ont tendance à diminuer significativement leur consommation quotidienne de nourriture par unité de masse. Les souris transgéniques consomment plus de sucroses que de moulée standard, une tendance qui ne varie pas avec l'âge. En revanche, les souris normales consomment moins de sucroses que de moulée et, en vieillissant, intègrent une proportion progressivement moins grande de sucrose dans leur régime. Chez les souris des deux types, il y a une relation unitaire entre la consommation quotidienne de protéines et la masse corporelle, ce qui résulte en une ali...

Hormonal control of aging in rodents: The somatotropic axis

“…Further support for a relationship between small body size and longevity is derived from reports showing that mice selected for reduced body sizes live longer (Roberts, 1961). In contrast to GH or IGF-1 deficiencies, animals overexpressing GH are significantly larger (30–60%) than wild-type controls (Shea et al, 1987; Wanke et al, 1992; Rollo et al, 1999). de Magalhães et al (2005) used Gompertz analysis to show that GH and the GH receptor statistically influence aging, while IGF1R and the insulin receptor (IR) do not.…”

“…As mentioned previously, reproductive senescence occurs earlier in transgenic mice with infertility appearing at 5–7 months of age (Bartke et al, 1994). Declines in cognitive function have also been observed at much younger ages in GH transgenic mice (Meliska et al, 1997; Rollo et al, 1999). Finally, evidence that cells from GH transgenic mice exhibit a reduced capacity to replicate is also consistent with accelerated aging (Pendergrass et al, 1993).…”