Levels of pituitary growth hormone (GH) messenger RNA (mRNA) were compared in groups of genetically obese (fa/fa) and lean (Fa/-) littermate male Zucker rats at four different ages, 3,5,9, and 11 weeks, in order to determine the earliest age at which a difference between the two groups could be detected. No difference was seen in three-week-old animals. Five weeks of age was the earliest time at which the level of GH mRNA was significantly decreased in the obese rats; this decrease was present at all subsequent ages. Mean serum growth hormone levels were lower in obese animals at all ages, but the differences were not statistically significant because of the large individual variation associated with the pulsatile nature of GH release. The earliest Occurrence of differences in GH mRNA level is later than some of the obesity associated abnormalities present in adipose tissue. The earliest time of the GH mRNA differences can be associated with the time when decreased protein deposition is initially seen in the obese rats. Because of this association, decreased GH mRNA may enhance the development of obesity.
Key words: obesity, genetically obese Zucker rat, growth hormone, messenger RNA, adipose tissue
The genetically obese Zucker rat (fa/fa) [ 11 manifests a variety of endocrinological abnormalities, one of which is the impaired release of growth hormone (GH). Studies of plasma samples using both single point determinations [2] and pulsatile 6 h patterns [3] have shown that the obese male rats have lower mean G H and fewer peaks of lower magnitude than age-matched lean controls. In an attempt to determine the molecular basis of this abnormality, we [4] have compared levels of G H mRNA in the pituitary glands of obese and lean Zucker rats. Adult male obese rats have significantly less pituitary GH mRNA than lean littermates, as measured in individual pituitaries by dot blot analysis and in pooled pituitary samples by slot blot and Northern hybridization analyses.
Abbreviations used: GAPDH, glyceraldehyde-3-phosphate dehydrogenase; GH, growth hormone; GHRH, growth hormone releasing hormone; mRNA, messenger RNA; PRL, prolactin; SEM, standard error of the mean.