Sl. Asa et al., Evidence for growth hormone (GH) autoregulation in pituitary somatotrophs in GH antagonist-transgenic mice and GH receptor-deficient mice, AM J PATH, 156(3), 2000, pp. 1009-1015
Citations number
28
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research Diagnosis & Treatment
Growth hormone (GH) modulates the hypothalamic release of somatostatin and
GH-releasing hormone; however, there has been no evidence of GH autoregulat
ion on the pituitary somatotroph. To determine the effects of GH on its own
regulation, we examined the pituitaries of giant transgenic mice expressin
g a GH agonist (E117L), dwarf transgenic mice expressing a GH antagonist (G
119K), and dwarf mice devoid of the GH receptor/binding protein (GHR/BP). I
n the E117L, transgenic mice, the number and distribution of pituitary GH-i
mmunoreactive cells were unchanged from nontransgenic littermate controls;
an ultrastructural examination revealed typical, densely granulated somatot
rophs. In contrast, the pituitaries of the G119K mice contained both modera
tely granulated somatotrophs and a sparsely granulated (SG) population with
well-developed synthetic organelles and a distinct juxtanuclear globular G
H-staining pattern, GHR/BP-deficient mice exhibited a marked reduction in t
he intensity of cytoplasmic GH immunoreactivity; however, prominent GH stai
ning in the juxtanuclear Golgi was seen. GH-immunoreactive cells were incre
ased in number, and the reticulin network pattern was distorted; stains for
proliferating cell nuclear antigen confirmed mild hyperplasia, Electron mi
croscopy showed that the somatotrophs were hyperactive SG tells with promin
ent endoplasmic reticulum membranes, large Golgi complexes, and numerous mi
tochondria, These findings are consistent with synthetic and secretory hype
ractivity in pituitary somatotrophs due to the reduced GH feedback regulati
on, The changes are most striking in animals that are devoid of GHR/BP and
less marked in animals expressing a GH antagonist; both models had reduced
insulin-like growth factor-I levels, but the more dramatic change in the GH
R/BP animals can be explained by abrogated GH signaling, This represents th
e first evidence of direct GH feedback inhibition on pituitary somatotrophs
, which may have implications for the use of GH analogs in different clinic
al settings.