To determine the effects of spaceflight on the anterior pituitary glan
d, the adenohypophyses of rats after a 7-day spaceflight aboard the sp
ace shuttle Endeavor (STS-54) were investigated by histology, immunohi
stochemistry, morphometry, electron microscopy, and in situ hybridizat
ion and were compared with synchronous control rats. Morphometry revea
led the corticotrophs of spaceflown rats to be significantly enlarged,
demonstrating 46-48% increases in mean cell, nuclear, and cytoplasmic
areas. These corticotrophs also exhibited striking ultrastructural si
gns of heightened secretory activity. Furthermore, their expression of
proopiomelanocortin mRNA, the transcript encoding the precursor prote
in from which adrenocorticotropic hormone is posttranslationally cleav
ed, was also significantly enhanced, a finding consistent with their h
ypersecretory state. Gonadotrophs also exhibited significant increment
s in mean nuclear, cell, and cytoplasmic areas of 22, 45, and 51%, res
pectively; however, they were not accompanied by ultrastructural evide
nce of increased secretory function. There were no morphological chang
es in somatotrophs, lactotrophs, or thyrotrophs, nor were there any si
gnificant changes in the overall frequency of any one adenohypophyseal
cell type in comparison with control. The structural integrity of all
adenohypophyseal secretory and vascular elements was preserved after
spaceflight, as there was neither evidence of necrosis nor other forms
of cellular injury in spaceflown specimens. Capillaries were patent,
and neither endothelial damage nor thrombosis was noted. These data su
ggest that spaceflight is accompanied by a selective morphological res
ponse in the anterior pituitary, one characterized by hypertrophy of b
oth corticotrophs and gonadotrophs and by enhanced endocrine activity
of the former.