Paul Licht - US grants

The goal of this proposal is to obtain basic information on the mechanisms by which the synthesis and secretion of pituitary hormones are regulated in ectothermal vertebrates The initial focus will be on hypothalamic factors that control thyrotropin (TSH) and gonadotropin (FSH and LDH secretion and on peripheral factors that modulate pituitary sensitivity to these factors in reptiles and amphibians. The young turtle will serve as a model reptilian system and the bullfrog will serve as an amphibian model, with limited comparisons with other orders. A. TSH Secretion: TSH regulation will focus on the role of the hypothalamic tripeptide, thyrotropin-releasing hormone (TRH), whose role in amphibians and rrptiles is poorly understood. We will also examine actions of potential stimulators and inhibitors from the brain and periphery, especially thyroid hormones, that may modulate pituitary responsiveness to TRH. Acute and chronic thermal effects on pituitary responsiveness will be examined in the context of exogeous control. Attempts will be made to analyze pituitary growth hormone and prolactin responses concomitantly in all studies, and in vitro thyroidal TSH sensitivity will be measured in parallel. B. Gonadotropin Secretion: Studies on the regulation of gonadotropin will have two foci:1) The role of steroids in modulating pituitary sensitivity to gonadotropin releasing hormone will be studied in relation to the ontogeny and maintenance of sexual dimorphism in responsiveness to this hyhpothalamic peptide. 2) Attention will be directed for the first time to the role of nonsteroidal gonadal secretions (based on mammalian inhibin) in differentially modulating pituitary FSH and LH secretion. These studies should provide a foundation for understanding the evolution of hypothalamo-pituitary regulation and its integration with peripheral endocrine targets in ectothermal tetrapods.

This project will take advantage of unique aspects of the hypothalamic-pituitary system in a common species of turtle (Pseudemys scripta) and frog (Rana pipiens) to study the dynamic relationship between brain peptide regulation of pituitary function and its modulation by peripheral feedback in relation to gonadal and thyroidal function. The turtle pituitary model will be used to study responsiveness of TSH secretion and environmental regulation of TSH secretion with emphasis on plasma binding proteins. Thyroxine binding protein will be purified and characterized for studies on its physiological role in the regulation of thyroid hormone transport and function in hopes of developing a model for understanding the evolution and function of thyroxine binding globulins. The demonstrated resistance of the frog pituitary to desensitization by gonadotropin-releasing hormone (GnRH) will be exploited to study the action of this neuropeptide on gonadotropin biosynthesis and its modulation by steroids. Parallel measurements of GnFH in the hypothalamus willl seek to determine how steroids influence pituitary regulation by actions in the brain.//

9419310 Licht This project will examine the molecular biology and physiology of an unusual dual-function blood binding protein. Based on preliminary data, this protein has structural similarity to vitamin-D-binding protein (VDBP), but Dr. Licht has determined that it also serves as a high affinity thyroid hormone binding protein (TBP); normally these two hormones are transported by very different types of protein. He will attempt to identify the structural features that permit this mixed function and study how the synthesis of the binding protein in the liver is regulated by hormones in order to test the hypothesis that it may be involved in the thyroidal regulation of growth or vitamin D utilization. ***