Objectives:Preliminary results from a rat pituitary cell culture experiment flown on STS-8 indicated that subsequent release of growth hormone (GH) from these cells at unit gravity might be impaired relative to that from ground-based control cells. Since GH exerts control over metabolic activities and macromolecule biosynthesis in a number of target tissues, impaired GH cell function in microgravity could conceivably participate in atrophy of those targets.
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Approach:
Pituitary glands were dissociated into single cell suspensions with viabilities greater than 95%. GH cell function in somatotrophs prepared from pituitary glands of rats exposed to microgravity were compared with those from corresponding controls. Somatotroph numbers were determined by flow cytometric immunofluorescence. Western blot analysis of alkaline (pH 8) cell extracts or culture media was done by electrophoresis followed by staining for GH variants by enzyme-linked immunoassay. For culture, 2.5x103 cells/well were maintained for six days with an intervening medium change on the third day. GH was assayed by RIA or 3T3 cell bioassay. For determination of GH cell function in vivo, cells were implanted into the lateral ventricles of 100 g rats using the hollow fiber encapsulation procedure. After sixteen days, tibial plates of recipients were measured to provide an index of long bone growth resulting from the implantation.
Results:
Pituitary growth hormone cells from glands of rats flown on SL-3 contained two to three times more intracellular hormone than controls, but released significantly less GH in subsequent in vitro and in vivo tests. After implantation into hypophysectomized rats, cells from both sizes of flight rats released ~50% as much GH relative to those from the control group. These diminished GH secretory patterns cannot be attributed simply to changes in variant forms of the GH molecule(s), though, since Western blot profiles in both intracellular and secreted GH revealed only minor differences in concentration and number of GH variants. Since the balance between somatostatin and GH releasing hormone presumably regulates hormone secretion in vivo, it is possible that microgravity alters their ratio to bring about high intracellular GH levels and lower release rates. As encapsulated cells were in an environment where they were exposed to hypothalamic regulatory peptides, one could also suggest that experimental cells were less sensitive to these peptides as a result of microgravity.
Grindeland RE, et al. Changes in Pituitary Growth Hormone Cells Prepared from Rats Flown on Spacelab 3. American Journal of Physiology 1987; 252:R209-15.
Grindeland RE, et al. Does Altered Growth Hormone Play a Role in Muscle Atrophy of Simulated Weightlessness?. Space Life Science Symposium: Three Decades of Life Science Research in Space 1987, NASA TM-108002: 82-3.
Hymer WC, et al. Microgravity Associated Changes in Pituitary Growth Hormone (GH) Cells Prepared from Rats Flown on Spacelab 3. Abstract S-197. Proceedings of the Seventh Annual Meeting on the IUPS Commission on Gravitational Physiology; 1985 Oct 13-18; Niagara Falls(NY).
Hymer WC, Grindeland R, Farrington M, Fast T, Hayes C, Motter K, et al. Microgravity Associated Changes in Pituitary Growth Hormone (GH) Cells Prepared from Rats Flown on Spacelab 3. Abstract 83.9. 36th Annual Fall Meeting of the American Physiological Society; 1985 Oct 13-18; Buffalo(NY): 377.
Hymer WC, Grindeland R, Farrington M, Fast T, Hayes C, Motter K, et al. Microgravity Associated Changes in Pituitary Growth Hormone (GH) Cells Prepared from Rats Flown on Spacelab 3. Physiologist 1985; 28(6 Suppl):S197-8.
Motter K, et al. Effects of Microgravity on Rat Pituitary Growth Hormone (GH) function: Comparison of Results of the SL-3 Mission with Rat "Unloading" on earth. Space Life Science Symposium: Three Decades of Life Science Research in Space 1987, NASA TM-108002: 52-3.
Kraemer WJ, Mastro AM, Gordon SE, Koziris LP, Bush JA, Volek JS, Staron RS, French DN, Sharman MJ, Jemiolo B, Deschenes MR, Hymer WC.. Responses of plasma proenkephalin peptide f in rats following 14 days of spaceflight. Aviat Space Environ Med 2004; 75:114 –7.
Count, Growth hormone cells (Somatotroph), pituitary, rat, Flow cytometry immunofluorescence