Hypophysiotropic somatostatin expression during postnatal development in growth hormone-deficient Ames dwarf mice: mRNA in situ hybridization.

Abstract

Lifelong deficiency of growth hormone (GH) in spontaneous or transgenic dwarf mice has been shown to be accompanied by reduced hypophysiotropic somatostatin (somatotropin release-inhibiting hormone, SRIH) expression in hypothalamic anterior periventricular nucleus (PeN). However, the postnatal developmental pattern of SRIH expression in the absence of GH is unknown. Therefore, SRIH mRNA levels in GH-deficient Ames dwarf (df/df) mice and normal (DF/?) littermates were determined both in adults, to compare with other GH-deficient models, and at selected days of postnatal development, to determine the effects of GH deficiency on SRIH neuron development. DF/? and df/df mice of both sexes at postnatal ages 1, 3, 7, 14, 21 and 60 days (adult) were examined. In situ hybridization and image analysis were used to quantify the relative abundance of total SRIH mRNA in the PeN, and SRIH mRNA per cell was determined in PeN and medial basal hypothalamus (MBH). In adult df/df mice, total PeN SRIH mRNA was 45% (p < 0.05) of that in DF/? littermates, which is consistent with studies of other GH-deficient dwarf mice. In developing animals, SRIH expression in the PeN of DF/? mice began at 3 days of age and increased at subsequent ages to reach adult levels. In df/df mice, PeN SRIH mRNA levels at 60 days were significantly greater than at 1-21 days of age (p < 0.05). However, levels were not different over 1-21 days of age, and were consistently lower in df/df than DF/? mice. The difference in total PeN SRIH mRNA between df/df and DF/? mice was statistically significant at 7 days, and at each subsequent age. There were no differences between DF/? and df/df mice in the number of grains per cell in either PeN or MBH at any age. Thus, the reduced total hypophysiotropic SRIH mRNA in GH-deficient Ames dwarf mice appears developmentally shortly after initial detectability of SRIH in the PeN. Because SRIH mRNA per cell was the same for DF/? and df/df mice, the decreased total mRNA in dwarfs suggested reduced SRIH cell numbers in PeN, which was corroborated by immunocytochemical findings. The reduction of SRIH in df/df mice at 7 days of age suggests that GH production during embryonic or very early postnatal development is important to activation of PeN SRIH transcription.