HYPOPHYSIOTROPIC SOMATOSTATIN EXPRESSION DURING POSTNATAL-DEVELOPMENTIN GROWTH HORMONE-DEFICIENT AMES DWARF MICE - PEPTIDE IMMUNOCYTOCHEMISTRY

Based on previous findings that the inhibitory hypophysiotropic factor somatostatin (somatotropin-release-inhibiting hormone, SRIH) is marke dly reduced in growth hormone (GH)-deficient transgenic or spontaneous Snell dwarf mice, the present study was undertaken to determine wheth er hypophysiotropic SRIH expression was reduced in a type of dwarf mou se (Ames, df/df) in which SRIH had not been assessed, and whether the supposed reduction was present throughout life or was the result of re gression after initial normal differentiation. Brain sections from nor mal (DF/?) and df/df mice were immunostained for SRIH using both stand ard and 'Elite' avidin-biotin complex reagents (Vectastain kits, Vecto r Laboratories, Inc., Burlingame, Calif., USA). Selected adult mice we re treated with intracerebroventricular colchicine to maximize SRIH re tention in perikarya. The developmental pattern of hypophysiotropic SR IH was assessed in brains of DF/? and df/df mice at 1, 3, 7, 14, 21, 6 0, and 90 days (d) postnatally. SRIH-immunoreactive neurons in the ant erior periventricular nucleus (PeN) were quantified at each age. Altho ugh the use of Elite reagents or Elite and colchicine pretreatment inc reased (p < 0.001) the number of immunoreactive cells that were detect able in adult (60- to 90-day-old) df/df mice, the number of PeN SRIH n eurons was reduced to 28% (p < 0.01) in untreated, and to 47% (p < 0.0 1) in colchicine-treated, df/df compared with DF/?. mice, In other CNS areas, SRIH immunostaining was comparable for df/df and DF/? mice, in cluding neuron numbers in the medial basal hypothalamus of untreated m ice. 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, SRI H cells were first detectable consistently in normals at 3 d, and in d warfs at 7 d.In DF/? mice, numbers of immunoreactive SRIH perikarya in creased from 3 to 21 d, then plateaued. In dwarfs, SRIH cell numbers i ncreased through 14 d. Numbers of SRIH perikarya were lower in df/df t han in DF/? at 7, 14, 21, 60, and 90 d (all p < 0.05 or less). Thus, i n Ames dwarf mice, as in other GH-deficient models, SRIH is markedly r educed in hypophysiotropic, ME-projecting neurons. The developmental p attern of hypophysiotropic SRIH in Ames dwarf mice is different from t hat of hypophysiotropic dopaminergic (DA) neurons in these animals, wh ich are also prolactin (PRL)-deficient. Although DA levels and cell nu mber; are reduced markedly in adult df/df mice, both parameters have b een found to be comparable to those of DF/? mice for the first 2-3 wee ks postnatally. The consistent PeN SRIH deficit in dwarfs may reflect the importance of GH feedback earlier in development, because GH produ ction in normal mice begins before birth, whereas PRL is not detectabl e until 7 d postnatally. The findings indicate that absent GH producti on has a marked negative effect on differentiation and levels of pepti de expression in hypophysiotropic SRIH neurons.