MOLECULAR ENDOCRINOLOGY OF THE UTERUS

点击翻译按钮获取中文摘要

DESCRIPTION: (Adapted from applicant's description) The glycoprotein hormone human chorionic gonadotropin (hCG) has been demonstrated to have direct effects on uterine metabolism. hCG is a member of a family of dimeric hormones including luteinizing hormone (LH), follicle stimulating hormone (FSH) and thyrotropin (TSH), that share a common alpha subunit and have unique beta-subunits. Studies from the investigator's laboratory and others have suggested that the alpha-subunit of hCG has a role in the regulation of prolactin production by uterine myometrium and decidua. However, the mechanism of this effect is not understood because alpha-subunit alone appears to have no effect through the known LH/hCG receptor. Furthermore, although it has been hypothesized that there are receptors on non-gonadal tissues including human endometrium and myometrium for LH/hCG, these studies have significant limitations that compromise the power of their conclusions. The hypothesis is that a unique receptor transduces the actions of hCG and/or alpha-subunit in the human uterus. The aim of this proposal is to characterize, using the techniques of molecular biology and molecular genetics, the known receptors for these hormones and to clone a unique receptor in the human uterus. These studies will define potentially a new level of pituitary/uterine interaction independent of gonadal hormonal influences. They may also lead to a better understanding of the molecular endocrinology of the human uterus. The specific aims of this proposal are: 1. To clone a unique receptor for hCG and/or alpha-subunit in the human uterus. 2. To quantitate and determine physiologic expression for this unique receptor(s) in the human uterus. 3. To identify genes transcriptionally regulated by the action of the ligands for this receptor(s) in the human uterus.