FUNCTION AND HORMONAL REGULATION OF ALPHA-FETOPROTEIN IN IMMATURE FEMALE RATS

NELLIE SUE BURKE, Purdue University

Abstract

The relative rate of AFP synthesis in the liver of the neonatal rat declined immediately after birth and rose again between 2 and 5 days of age. It then declined slowly until 10 days and more rapidly afterwards. The neonatal rat kidney also synthesized AFP. No AFP synthesis was detected in the uterus, small intestine, brain, or spleen. Messenger RNA for AFP was also detected in neonatal liver and kidney but not in adult kidney, neonatal brain or small intestine. Evidence was found that glucocorticoids are physiologically involved in the postnatal AFP decline. Glucocorticoids caused a decrease in the relative rate of synthesis of AFP and in mRNA(,AFP) in the livers of neonatal rats. This effect was reversible. Adrenalectomy at 13 or 21 days led within 5 days to an AFP concentration which was elevated over the control but still declining. In contrast to liver, glucocorticoids had little effect on kidney AFP synthesis and mRNA(,AFP). Support was given for the hypothesis that the decline in AFP synthesis with age is related to the decrease in DNA synthesis which occurs during postnatal development. Glucocorticoids caused an inhibition in DNA synthesis in the liver, early eye opening, a slowing of body growth rate, and a change in the pattern of protein synthesis by the liver. Hydroxyurea, an inhibitor of DNA synthesis, caused some of the same changes in the protein synthesis pattern, including inhibition of AFP synthesis, that were seen with glucocorticoids. The inhibition of AFP and DNA synthesis and some of the changes which occur with glucocorticoids and hydroxyurea also occurred during postnatal development. A possible function for AFP was investigated. Because of its ability to bind estrogen, rat AFP has been proposed to function in the timing of the onset of puberty in the female. Serum AFP was lowered by injecting AFP antibody or dexamethasone and raised by injecting AFP. None of these treatments changed the time of onset of puberty.

Degree

Ph.D.

Subject Area

Biology

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