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The Ontogenesis of Human Fetal Hormones. IV. Somatostatin, Luteinizing Hormone Releasing Factor, and Thyrotropin Releasing Factor in Hypothalamus and Cerebral Cortex of Human Fetuses 10-22 Weeks of Age

Department of Pediatrics, University of California, San Francisco San Francisco, California 94143

^* Reprint address: M.M.G., Department of Pediatrics, University of California, San Francisco, San Francisco, California 94143.

Somatostatin, LRF, and TRF were measured by radioimmunoassay in extracts of hypothalami obtained from human fetuses between 10 to 22 weeks gestation. Iodinated LRF and somatostatin eluted mainly after the iodide peak (K_d 2), free of the unlabeled factor when purified on Sephadex G25 with 0.1M acetic acid as eluant. Of 3 anti- LRF sera used, one did not recognize any of 21 LRF fragments but could detect analogs with changes in position 2 and 8; a second only recognized the 7–10 C-terminal sequence, and the third was directed against positions 5–9. Hypothalamic or brain extracts produced parallel displacement in each radioimmunoassay.

Somatostatin was present in 43/44 fragments: mean content in 44 hypothalami was 14.9 ± 2.0 ng, concentration 16.8 ± 2.2 pg/mg; in 25/27 cerebral cortex tissues, 4.2 ±1.1 pg/mg. There was weakly positive correlation between hypothalamic somatostatin and gestational age in the 10 to 22 week period (r = 0.388, P < 0.01).

The mean content of LRF in 33/44 hypothalami was 1.53 ± 0.48 ng, concentration 1.45 ± 0.34 pg/mg. By Sephadex G25 exclusion chromatography, hypothalamic LRF coeluted with synthetic LRF. The concentration was no different when assayed either with the highly specific anti-LRF or the C-terminal antiserum; anti-LRF directed toward the sequence 5–9 of the LRF molecule was about 20% higher. In fetuses between 10 to 22 weeks there was no relation between the content or concentration of LRF, and sex or gestational age, and only small amounts of LRF were detected in 13/27 samples of cerebral cortex.

TRF was present in all 45 samples of hypothalami (14.6 ± 5.3 pg/mg) and cerebral cortex (12.5 ±4.2 pg/mg), with no observable trend as to sex or gestational age. The mean concentration in cerebral cortex samples corresponded to 85% of that found in hypothalami. Hypothalamic TRF co-eluted with synthetic TRF on Sephadex G25.

The substantial concentrations of LRF and TRF in fetal hypothalamus at mid-gestation correlate with the elevation of serum fetal pituitary gonadotropins and development of TSH secretion. Although the high levels of serum growth hormone at mid-gestation can be explicated by the unrestrained secretion of growth hormone releasing factor, the presence of somatostatin in the fetal hypothalamus and its increase with gestational age suggest a dual hypothalamic control of growth hormone. The fall in the concentration of serum growth hormone in late gestation may be mediated, in part, by increased release of somatostatin as well as a decrease in secretion of growth hormone releasing factor.

Supported in part by grants from the National Institutes of Child Health and Human Development and the National Institute of Arthritis, Metabolism, and Digestive Diseases, NIH, USPHS.

Received November 20, 1976.