The main interest of the principal investigator is to understand the processes by which various hormones control the gonads, with the hope that the knowledge gained will improve the identification, regulation and correction of human disorders associated with reproduction, and possibly other hormonally regulated systems. This interest has centered in the past, and will center in the foreseeable future, on the interaction of the gonadotropins with their receptors and the mechanisms by which they control the activity of adenylate cyclase. the proposed research will examine aspects of both the interests listed above by 1) investigating the interaction of LH/hCG with two putative types of hormone receptors in the corpus luteum, 2) investigating the role of guanyl nucleotides in the binding of LH/hCG to its receptors and in the modulation of adenylate cyclase, and 3) isolating and characterizing membrane and cytoplasmic factors which enhance adenylate cyclase activity in vitro. These binding and adenylate cyclase studies which are familiar to the principal investigator. The recent isolation of a membrane preparation from rat corpus luteum in which hCG and guanyl nucleotides modulate each others' binding will allow a thorough investigation of the phenomena. The membrane preparations will be further purified and used to examine the interaction of LH/hCG with its receptors in various membrane fractions, to examine the role of guanyl nucleotides and GTPase activity in hormonal stimulation of luteal tissue, to probe possible differences between the binding and actions of hCG and LH, and to determine the composition of the various hormone receptor complexes. Finally, an attempt will be made to isolate, using classical techniques such as precipitation, column chromatography, sucrose density gradient centrifugation and electrophoresis, and characterize one or more factors present in urea extracts of luteal membranes and the cytosol which have been shown to augment hormonally stimulated adenylate cyclase in the absence of GTP in vitro.
| McIlroy, P J (1992) Differences in the characteristics and distribution of rat luteal receptors for native and deglycosylated human choriogonadotropin. Biol Reprod 47:97-104 |
