This application seeks continued support for studies using the quantitative dry-autoradiographic-immunocytochemical (qdAI) method to analyze nuclear retention of 3H-gonadal hormones by individual cell types in situ. Biochemical evidence indicates that various factors modulate estrogen receptor levels and, consequently, estrogen uptake by target organs. Recent use of qdAI has verified this evidence and has shown further that modulation is often selectively confined to just one or two cell types within a heterogeneous target tissue. The proposed studies seek to 1) identify the factors and 2) reveal the mechanisms of action of factors that selectively modulate gonadal hormone retention by individual target cell types. 3H-estrogen (and later androgen and progestogen) uptake will be quantified in situ in single cell types of brain, pituitary and uterus after endocrine ablation or hormone pretreatment. Nuclear retention and receptor replenishment characteristics will be examined in each cell type. Hormone uptake will be studied with respect to development, especially puberty and "menopause", and will be examined in both normal and pathological tissues, in situ and in vitro. Increased knowledge of selective modulatory mechanisms will significantly advance our understanding not only of the control of reproduction but also of the regulatory mechanisms that are central to the fields of endocrinology, neuroendocrinology, pathology and development. By understanding the selective modulation of single cell types in a heterogeneous tissue we expand our potential to find hormonal analogs which both enhance therapeutic selectivity and decrease undesirable side effects.
NIH ExPorter
NIH ExPorter