Eugene C. Jorgensen

1164 TRANSPLACENTAL EFFECTS OF A THYROXINE ANALOG ON PHOSPHOLIPID SYNTHESIS IN FETAL RABBIT LUNG

To investigate the possible role of thyroid hormones in fetal lung maturation, we treated pregnant rabbits with 3,5-dimethyl-3′-isopropylthyronine (DIMIT), a thyroxine analog which binds to nuclear receptors in fetal lung. On days 24 and 25 of gestation does received diluent or 0.05-1 mg/kg DIMIT im; fetuses were studied on day 26. We found no effect of DIMIT on viability, body weight, lung weight, lung wet/dry ratio, or fetal plasma cortisol levels. NADPH-cytochrome C reductase, a known T4 inducible enzyme, was increased 64% (p<0.01) in fetal liver with 1 mg/kg DIMIT. Mean±SE values for the rate of 3H-choline incorporation into lecithin (pmol/mg tissue/h) by minced fetal lung and activity of phosphatidic acid phosphatase (PAPase, nmol/mg prot/min) in lung homogenate are shown below (*=p<0.001):Similar results were found for incorporation of 3H-glycerol.We conclude that DIMIT crosses the rabbit placenta and stimulates lecithin synthesis and PAPase activity in fetal lung. Since similar effects occur with glucocorticoid treatment, these two hormones may act in part by controlling the same enzyme.

Chapter 17. Non-steroidal Hormones and Their Antagonists

Publisher Summary A hormone is generally considered to be a discrete chemical substance that is produced in a gland and secreted into the body fluids. It produces a specific effect on the activities of other organs. The glandular hormones belong to this class. Recent advances are based on the structural variations of known hormones, structural elucidation of new hormones, and efforts of the initial syntheses of hormones whose structures have been proposed on the basis of degradation studies. The non-steroidal hormones reviewed in this chapter are composed primarily of amino acid derivatives and are limited to those whose structures are known, or have been proposed, and in which significant recent progress has been made in the synthesis of the hormone or of its analogs. In the structural elucidation of new hormones, recently, a number of peptides with intense pharmacological activities have been found to be generated by specific enzyme-catalyzed hydrolysis of plasma proteins; these have been called “tissue hormones.” The importance of active peptides, for full biological activity, has been emphasized. Variations in the nature and configuration of the peptide chain have led to less active or inactive analogs. Partial syntheses of the linear peptide, which contains 29 amino acids, have been reported by researchers, but biological activities have not yet been reported.