Effects of spaceflight on hypothalamic peptide systems controlling pituitary growth hormone dynamics

Immunohistochemical and in situ hybridization localization of peptides derived from, and mRNAs encoding, prepro-somatostatin (ppSS) and prepro-growth hormone-releasing factor (ppGRF) was carried out on hypothalami from rats flown on biosatellites COSMOS 1887 and 2044 to investigate possible effects of reduced gravity on central hypophysiotropic systems controlling growth hormone (GH) secretion. Results from the COSMOS 1887 mission indicated that both SS and GRF immunostaining in the median eminence were diminished in flight animals relative to controls; no differences between groups in staining for other peptidergic neurosecretory systems were apparent. Animals flown on COSMOS 2044 displayed a more pronounced depletion of GRF than SS immunoreactivity from neurosecretory terminals in the median eminence. In addition, flight animals displayed significant 46-50% reductions in the number and signal intensity of presumed hypophysiotropic cells in the arcuate nucleus expressing ppGRF mRNA; positively hybridized cells in the region surrounding the ventromedial nucleus were less markedly affected. Both indexes of ppSS mRNA levels in the anterior periventricular nucleus were similar in flight and control rats. An additional group of animals that experienced hindlimb suspension, a manipulation that mimics the effects of weightlessness on several parameters, did not differ from controls in any of the above measures. These data suggest that exposure to microgravity results in a preferential reduction in GRF peptide and mRNA levels in hypophysiotropic neurons, which may contribute to impaired GH secretion described previously in animals subjected to spaceflight. Effects of weightlessness are not mimicked by hindlimb suspension in this system.