EFFECTS OF BOVINE GROWTH-HORMONE (GH) EXPRESSION IN TRANSGENIC MICE ON SERUM AND PITUITARY IMMUNOREACTIVE MOUSE GH LEVELS AND PITUITARY GH-RELEASING FACTOR-BINDING SITES
A. Sotelo et al., EFFECTS OF BOVINE GROWTH-HORMONE (GH) EXPRESSION IN TRANSGENIC MICE ON SERUM AND PITUITARY IMMUNOREACTIVE MOUSE GH LEVELS AND PITUITARY GH-RELEASING FACTOR-BINDING SITES, Acta endocrinologica, 129(5), 1993, pp. 446-452
Pituitary and serum levels of homologous growth hormone (GH) and chara
cteristics of specific GH-releasing factor (GHRF) binding to pituitary
homogenates were examined in transgenic mice expressing bovine GH (bG
H) gene regulated by different promoters [mouse metallothionein-I (MT)
or phosphoenol-pyruvate carboxykinase (PEPCK)] and in their normal li
ttermates. Pituitary GH concentration and GHRF binding were reduced by
approximately 50% in transgenic MT-bGH mice in which serum bGH levels
were about 20 mug/l and by approximately 95% in transgenic PEPCK-bGH
mice in which serum bGH levels were tenfold higher. Suppression of pla
sma immunoreactive mouse GH (mGH) levels was detected in MT-bGH but no
t in PEPCK-bGH animals. presumably due to cross-reaction of the antise
rum employed with bGH. Scatchard plots of GHRF binding to washed homog
enates of pituitary glands from normal and young adult MT-bGH transgen
ic mice were curvilinear, indicating the presence of two types of bind
ing sites, with low and high affinities. Both types of binding sites w
ere reduced in number in MT-bGH transgenic mice without changes in the
ir affinity. In 5-7-month-old MT-bGH transgenic mice there were change
s in pituitary GH levels, in GHRF binding levels and in characteristic
s of GHRF binding that closely resembled the alterations described pre
viously in aging rats. We conclude that over-expression of heterologou
s GH genes in transgenic mice can lead to partial or virtually complet
e suppression of somatotroph function, depending on the levels of hete
rologous GH in the circulation, and that transgenic MT-bGH mice exhibi
t symptoms of remarkably early onset of neuroendocrine aging.