Influence of growth hormone deficiency on growth and body composition in rats: site-specific effects upon adipose tissue development

Abstract

Neonatal female rats were treated for 3 weeks (short term) or 8 weeks (long term) with antiserum to rat GH (anti-rGH) with or without replacement therapy with recombinant bovine GH (bGH). Body weight gain and tail length were significantly suppressed within the first 3 weeks and were even more markedly suppressed when treatment was continued for 8 weeks. When treatment was stopped in short-term-treated animals the rate of body weight gain recovered, although without evidence of catch-up growth. These effects were all normalized by concurrent treatment with bGH. Long-term anti-rGH treatment caused a profound reduction (80%) in the number of differentiated adipocytes in two internal fat depots, whilst the subcutaneous depot was only moderately affected (20%). In contrast, after recovery from short-term treatment with anti-rGH, the internal depots were only marginally decreased in both weight and adipocyte numbers, whereas the subcutaneous depot was actually doubled in size compared with controls, due entirely to an increase in the number of differentiated adipocytes. These data clearly demonstrate for the first time that GH is required for the differentiation of adipocytes in vivo. In addition, the results demonstrate distinct effects at different anatomical sites and suggest that GH may be one factor responsible for the differences described in numerous metabolic parameters and hormonal sensitivities of adipose tissue derived from different locations within the body.

Developmental aspects of adipose tissue in GH receptor and prolactin receptor gene disrupted mice: site-specific effects upon proliferation, differentiation and hormone sensitivity

“…In addition to identifying these site-specific effects, we also demonstrated, for the first time, that absence of the GHR creates intrinsic changes in adipocytes from this depot, which persist for at least 10 days in vitro. These findings confirm and extend a previous study where we examined the effects of an antiserum to GH which, when administered to neonatal rats, also produced major decreases in parametrial but not s.c. fat (Flint & Gardner 1993). Whilst the effects upon the parametrial depot described in our study clearly demonstrate that GH is required for adipocyte proliferation and differentiation in vivo, in similar fashion to that seen in 3T3-F442A cells in vitro, the site-specific effects of GH may in part explain the contradictory results obtained with different cell lines, or in comparisons of primary cell culture, where cells have originated from different anatomical sites.…”

Dietary obesity linked to genetic loci on chromosomes 9 and 15 in a polygenic mouse model.

“…There is a significant literature showing that manipulations of circulating growth hormone levels can have significant effects upon body composition in humans (30) and in animals (31,32). Furthermore, defects in growth hormone receptor function have been shown to be related to obesity in human Laron dwarfism (33).…”

Growth Hormone-dependent Differentiation of 3T3-F442A Preadipocytes Requires Janus Kinase/Signal Transducer and Activator of Transcription but Not Mitogen-activated Protein Kinase or p70 S6 Kinase Signaling

“…A major regulator of this process is growth hormone (GH), 1 which has been shown in several studies to promote the differentiation of preadipocytes both in vitro and in vivo (3)(4)(5)(6)(7)(8)(9). The dual effector theory has been proposed to explain the actions of GH upon differentiation of preadipocyte cells (3).…”