Microgravity-Induced Effects on Pituitary Growth Hormone Cell Function (PHCF): A Mechanism for Muscle Atrophy in Manned Space Flight

Endocrinology

Rattus norvegicus (Sprague-Dawley rat)
Flight culture vials: 165

Basal culture vials: 165, Delayed synchronous culture vials: 165

Altered Kit Container, Ambient Temperature Recorder, Refrigerator/Incubator Module

1) To establish the effect of microgravity on storage, synthesis, and secretion of GH by rat pituitary cells; 2) to study the effects of hydrocortisone and hypothalamic GH-releasing hormone (GHRH) on GH cells; 3) to determine whether these changes persist in vitro after flight; 4) to determine whether microgravity affects the molecular form of GH; and 5) to determine the effects of microgravity on the ultrastructure of the somatotroph and whether there is a difference in somatotrophs from the dorsal or ventral area of the pituitary gland, as well as from the high- vs. low-density somatotrophs contained in the pituitary.

Cells were divided into five location/density-based groups. After flight, cultures were tested for their responsiveness to a synthetic GHRH. Concentration of immunoreactive GH (iGH) released from the cells into the culture media was determined by enzyme immunoassay. Concentrations of biologically active GH in the culture media and extracts were measured using bioassays. High performance liquid chromatography was used to determine the molecular weights of GH released from flight and ground-control cells. Immunocytochemistry was used to identify GH cells and flow cytometry was used to study their cell morphology and to quantitate numbers of somatotrophs in each sample.

Image analysis of GH cells from mixed and high-density groups showed an increase in cytoplasmic areas of flight cells. There were no differences in area of the low-density group. Microgravity did not affect the release of iGH during flight or during the 6-day postflight period. Release of bGH was reduced in the high-density flight cells, but treatment with hydrocortisone raised the levels to that of the ground controls. Hydrocortisone had the opposite effect on low-density and mixed-density flight cells. A greater fraction of high molecular weight iGH was found in flight samples, but in general, neither microgravity or steroids had an effect on the size distribution of the hormone. Flight cells were less sensitive to GHRH than ground cells. No changes were seen in release of iGH between flight and ground-control cells of the dorsal or ventral regions; however, the release of bGH was reduced by half in ventral flight cells as compared to ventral ground-control cells. In summary, data show that changes in chemical and cellular makeup of cell cultures affect GH cell-response to microgravity.

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