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

Based on previous findings that the inhibitory hypophysiotropic factor somatostatin (somatotropin-release-inhibiting hormone, SRIH) is markedly reduced in growth hormone (GH)-deficient transgenic or spontaneous Snell dwarf mice, the present study was undertaken to determine whether hypophysiotropic SRIH expression was reduced in a type of dwarf mouse (Ames, df/df) in which SRIH had not been assessed, and whether the supposed reduction was present throughout life or was the result of regression after initial normal differentiation. Brain sections from normal (DF/?) and df/df mice were immunostained for SRIH using both standard and 'Elite' avidin-biotin complex reagents (Vectastain kits, Vector Laboratories, Inc., Burlingame, Calif., USA). Selected adult mice were treated with intracerebroventricular colchicine to maximize SRIH retention in perikarya. The developmental pattern of hypophysiotropic SRIH was assessed in brains of DF/? and df/df mice at 1, 3, 7, 14, 21, 60, and 90 days (d) postnatally. SRIH-immunoreactive neurons in the anterior periventricular nucleus (PeN) were quantified at each age. Although the use of Elite reagents or Elite and colchicine pretreatment increased (p < 0.001) the number of immunoreactive cells that were detectable in adult (60- to 90-day-old) df/df mice, the number of PeN SRIH neurons was reduced to 28% (p < 0.01) in untreated, and to 47% (p < 0.01) in colchicine-treated, df/df compared with DF/?, mice. In other CNS areas, SRIH immunostaining was comparable for df/df and DF/? mice, including neuron numbers in the medial basal hypothalamus of untreated mice. In postnatal development, SRIH was detectable in median eminence (ME) terminals at birth in some mice of both phenotypes, and at 3 d in all DF/? mice; ME SRIH was detectable in all mice by 7 d. In PeN, SRIH cells were first detectable consistently in normals at 3 d, and in dwarfs at 7 d. In DF/? mice, numbers of immunoreactive SRIH perikarya increased from 3 to 21 d, then plateaued. In dwarfs, SRIH cell numbers increased through 14 d. Numbers of SRIH perikarya were lower in df/df than in DF/? at 7, 14, 21, 60, and 90 d (all p < 0.05 or less). Thus, in Ames dwarf mice, as in other GH-deficient models, SRIH is markedly reduced in hypophysiotropic, ME-projecting neurons. The developmental pattern of hypophysiotropic SRIH in Ames dwarf mice is different from that of hypophysiotropic dopaminergic (DA) neurons in these animals, which are also prolactin (PRL)-deficient. Although DA levels and cell numbers are reduced markedly in adult df/df mice, both parameters have been found to be comparable to those of DF/? mice for the first 2-3 weeks postnatally. The consistent PeN SRIH deficit in dwarfs may reflect the importance of GH feedback earlier in development, because GH production in normal mice begins before birth, whereas PRL is not detectable until 7 d postnatally. The findings indicate that absent GH production has a marked negative effect on differentiation and levels of peptide expression in hypophysiotropic SRIH neurons.