Effects of Space Flight on Anterior Pituitary Receptors

Endocrinology

Rattus norvegicus (Sprague-Dawley rat)
Male

Synchronous, Delayed synchronous

Ambient Temperature Recorder, Animal Enclosure Module, Research Animal Holding Facility

It has been found that the secretion of growth hormone (GH) is decreased during exposure to actual or simulated microgravity. GH is secreted by somatotrophs in the anterior pituitary and is the primary regulator of growth. The release of GH is under the control of two hypothalamic peptides: stimulatory growth hormone releasing factor (GRF) and the inhibitor somatostatin (SS). GRF acts on the specific cell receptors of somatotrophs, thus activating the release of GH. Increased numbers of GH content and GH granules in somatotrophs after space flight suggests that the decrease in GH secretion is not due to a decrease in synthesis of GH but rather a decrease in secretion. The hypothesis of this experiment is that space flight causes an alteration in the number and/or affinity of GRF receptors that accounts for the decrease in GH secretion.

Pituitaries harvested from SLS-1 and stored at -70 °C for 2.5 years were homogenized in a Tris buffer (pH 7.4) to a final concentration of 20 mg pituitary tissue/ml of buffer. These homogenates were then assayed using iodinated GRF (human) as the radioligand and decreasing concentrations of cold GRF (rat) as the cold competitor. Concentrations of cold GRF were 10^-6 M, 10^-8 M, 10^-10 M, and 10^-12 M. Tubes containing the homogenate, the iodinated GRF, and the cold GRF were incubated for 2 hours and immersed in ice cold water to stop the reaction. Samples from each tube were centrifuged and the resulting pellets were counted using a Packard Gamma counter. Assays were performed using five groups of glands from SLS-1 as well as fresh glands for comparison purposes.

Total binding from glands of SLS-1 rats and glands from fresh rats were comparable, suggesting total protein content was similar. However, specific binding was not seen in any of the SLS-1 rat homogenates. Assays from fresh glands showed a dose-response curve, indicating that binding of iodinated GRF to the pituitary receptors is specific and inhibited in a dose-dependent manner by increasing concentrations of cold GRF. The failure of flight samples to show specific binding sites suggests that the flight samples were compromised; no conclusions can be reached regarding alterations in GRF receptors due to exposure to microgravity.

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