Abstract

The aim of the proposed study is to interrelate precisely steroid hormone receptor containing cells to the peptidergic and aminergic system in rat brain. This will be studied by immunohistochemistry and by combined autoradiography and immunohistochemistry. The ontogeny of estrogen receptor containing cells in fetal brain at different times of development will be determined by immunohistochemistry, using monoclonal receptor antibodies. The effects of progesterone on intracellular distribution of estradiol receptor will be assessed. Neurons containing both estradiol and progesterone receptors will be identified using estradiol receptor antibody for immunostaining and 3H ORG2058, a synthetic progestin for nuclear uptake of radioactivity. A double immunostaining procedure will be applied to interrelate estrogen receptor containing cells to peptide or neurotransmitter producing cells. Specifically an attempt will be made to determine the interaction between pro-luteinizing hormone releasing hormone (GnRH associated peptide, GAP) producing neurons and estrogen receptor containing neurons as well as neurotransmitter systems. Effects of estradiol on levels of preproenkephalin and proopiomelanocortin mRNAs in certain populations of brain neurons will be determined by in situ hybridization histochemistry utilizing cDNA or cRNA to preproenkephalin and proopiomelanocortin. Study on colocalization of 3H ORG2058 and antibodies to neuropeptides will be conducted for the characterization of progestin target cells. The results of this study will help in understanding the role of steroid hormones in the central regulation of neuroendocrine function and behavioral response.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS017479-06
Application #
3397601
Study Section
Reproductive Biology Study Section (REB)
Project Start
1982-09-01
Project End
1990-11-30
Budget Start
1988-12-01
Budget End
1989-11-30
Support Year
6
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
University of North Carolina Chapel Hill
Department
Type
Schools of Medicine
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599

  Publications

Wong, C; Kelce, W R; Sar, M et al. (1995) Androgen receptor antagonist versus agonist activities of the fungicide vinclozolin relative to hydroxyflutamide. J Biol Chem 270:19998-20003
Zhou, Z X; Sar, M; Simental, J A et al. (1994) A ligand-dependent bipartite nuclear targeting signal in the human androgen receptor. Requirement for the DNA-binding domain and modulation by NH2-terminal and carboxyl-terminal sequences. J Biol Chem 269:13115-23
Junker, J; Sommer, J R; Sar, M et al. (1994) Extended junctional sarcoplasmic reticulum of avian cardiac muscle contains functional ryanodine receptors. J Biol Chem 269:1627-34
Shughrue, P J; Sar, M; Stumpf, W E (1992) Progestin target cell distribution in forebrain and midbrain regions of the 8-day postnatal mouse brain. Endocrinology 130:3650-9
Kemppainen, J A; Lane, M V; Sar, M et al. (1992) Androgen receptor phosphorylation, turnover, nuclear transport, and transcriptional activation. Specificity for steroids and antihormones. J Biol Chem 267:968-74
Shughrue, P J; Stumpf, W E; Elger, W et al. (1991) Progestin receptor cells in mouse cerebral cortex during early postnatal development: a comparison with preoptic area and central hypothalamus using autoradiography with [125I]progestin. Brain Res Dev Brain Res 59:143-55
Simental, J A; Sar, M; Lane, M V et al. (1991) Transcriptional activation and nuclear targeting signals of the human androgen receptor. J Biol Chem 266:510-8
McGimsey, W C; Cidlowski, J A; Stumpf, W E et al. (1991) Immunocytochemical localization of the glucocorticoid receptor in rat brain, pituitary, liver, and thymus with two new polyclonal antipeptide antibodies. Endocrinology 129:3064-72
Shughrue, P J; Stumpf, W E; Elger, W et al. (1991) Progestin receptor cells in the 8-day-old male and female mouse cerebral cortex: autoradiographic evidence for a sexual dimorphism in target cell number. Endocrinology 128:87-95
Sar, M; Lubahn, D B; French, F S et al. (1990) Immunohistochemical localization of the androgen receptor in rat and human tissues. Endocrinology 127:3180-6

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