Cosmos 1887 / Bion 9

C2044-27.2

Title of Study

Growth Hormone Regulation, Synthesis and Secretion in Microgravity: II. Hypothalamic GH-Releasing Factor, Somatostatin Immunoreactivity, and mRNA Levels

Science Discipline

Regulatory Physiology

Investigator
Institute
P.E. Sawchenko
The Salk Institute, La Jolla
 
 
Co-Investigators
Institute
Vale, W.
The Salk Institute, La Jolla
Arias, C.
The Salk Institute, La Jolla
Krasnov, I.B.
Institute of Biomedical Problems

Research Subjects

Rattus norvegicus (Wistar Rat)

5 Flight Males

Ground Based Controls

5 Synchronous, 5 Tail-Suspended

Key Flight Hardware

Cosmos 2044 Russian Hardware Suite

Objectives/Hypothesis

Immunohistochemical analysis from a previous investigation (Cosmos 1887) suggested preferential effects on hypophysiotropic principles involved in the regulation of growth hormone secretion and synthesis. To provide an additional, more penetrating analysis, this study attempted to complement immunohisto- chemical analysis of growth hormone-releasing factor (GRF) and somatostatin (SS) staining with quantitative, in situ assessments of messenger RNAs encoding the precursors for both these hormones.

Approach or Method

Longitudinally bisected hypothalami were sectioned 20 µm thick and stained with a conventional avidin-biotin-immunoperoxidase procedure. For GRF, a polyclonal antiserum raised in rabbits against synthetic rat GRF[1-43] was used; for SS an antiserum against SS-28 was employed. For in situ hybridization, plasmid was linearized, and labeled antisense probes were generated using SP6 RNA polymer- ase and 35-S-UTP. Sections were dehydrated and exposed to x-ray films, later coated with a liquid autoradiographic emulsion, then finally developed. Cell and grain counting procedures were used to compare the strengths of mRNA signals on autoradiographic material.

Results

The results complement and extend analyses of the previous study, which showed roughly comparable decrements in both SS and GRF-IR in the median eminence of flight animals; though, in this study flight hypophysiotropic fibers were more severely depleted. In comparison to synchronous and tail-suspended animals, the ppGRF mRNA signal in the arcuate nucleus of flight animals was significantly reduced, while ppSS mRNA levels were not significantly altered. While this effect on indices of ppGRF mRNA levels may be representative of an influence exerted at the level of ppGRF gene transcription, alternate explanations (e.g., effects on mRNA stability) cannot be discounted.

Publications

Experiment Reference Number: C2044-27.2

Sawchenko, P.E. et al.: Effects of Spaceflight on Hypothalamic Peptide Systems Controlling Pituitary Growth Hormone Dynamics. Journal of Applied Physiology, supl., vol. 73, no. 2, 1992, pp. S158-S165.

Sawchenko, P.E. et al.: Growth Hormone Regulation, Synthesis and Secretion in Microgravity: II. Hypothalamic GH-Releasing Factor, Somatostatin Immunoreactivity, and mRNA Levels in Microgravity. Final Reports of the U.S. Experiments Flown on the Soviet Biosatellite Cosmos 2044. Vol. 2. J.P. Connolly, R.E. Grindeland, and R.W. Ballard, eds., NASA TM-108802, 1994, pp. 173-182.

¥ = publication of related ground-based study