In this proposal we plan to study endocrine factors that control aromatization in the central nervous system (CNS). Preliminary data suggest that brain aromatization in rodents is controlled by testosterone. Now we will localize this activity to specific regions and nuclei of the CNS, study specificity of hormone action and thresholds for its induction by steroid hormones. Further analysis of aromatase activity (AA) will be obtained in proposed studies that will investigate the necessity of androgen receptors, for the inductive action of androgen on brain AA. We postulate that AA is controlled differently in different parts of the CNS and that different species of the enzyme complex are distributed regionally within the brain. Experiments are proposed that will investigate these possibilities. Some studies performed first on rodents will be expanded to include nonhuman primates (Macaca mulatta). In the primate studies we will localize aromatase within the CNS and determine the effects of castration and androgen replacement on its activity. We wish to know whether AA and GnRH quantified by RIA are localized within the same brain regions. We have developed a new antisera to GnRH that appears promising for these studies. A developmental study is proposed in which placental aromatase will be solubilized and purified by column chromatography. Antibodies will be produced with the intent of performing immunocytochemistry at some future date. The data that will be generated in rodents will be important additions to the existing literature (which is quite small) on endocrine factors that control aromatization in the brain. The primate studies are important because: a) They represent the first real attempt to identify control mechanisms for aromatase and their regional distribution within the brain of non-human primates.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
Project #
Application #
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Oregon Health and Science University
Schools of Medicine
United States
Zip Code
Pereyra-Martinez, A C; Roselli, C E; Stadelman, H L et al. (2001) Cytochrome P450 aromatase in testis and epididymis of male rhesus monkeys. Endocrine 16:15-9
Roselli, C E; Resko, J A (2001) Cytochrome P450 aromatase (CYP19) in the non-human primate brain: distribution, regulation, and functional significance. J Steroid Biochem Mol Biol 79:247-53
Resko, J A; Pereyra-Martinez, A C; Stadelman, H L et al. (2000) Cellular observations and hormonal correlates of feedback control of luteinizing hormone secretion by testosterone in long-term castrated male rhesus monkeys. Biol Reprod 63:872-8
Resko, J A; Pereyra-Martinez, A C; Stadelman, H L et al. (2000) Region-specific regulation of cytochrome P450 aromatase messenger ribonucleic acid by androgen in brains of male rhesus monkeys. Biol Reprod 62:1818-22
Abdelgadir, S E; Roselli, C E; Choate, J V et al. (1999) Androgen receptor messenger ribonucleic acid in brains and pituitaries of male rhesus monkeys: studies on distribution, hormonal control, and relationship to luteinizing hormone secretion. Biol Reprod 60:1251-6
Choate, J V; Slayden, O D; Resko, J A (1998) Immunocytochemical localization of androgen receptors in brains of developing and adult male rhesus monkeys. Endocrine 8:51-60
Abdelgadir, S E; Roselli, C E; Choate, J V et al. (1997) Distribution of aromatase cytochrome P450 messenger ribonucleic acid in adult rhesus monkey brains. Biol Reprod 57:772-7
Roselli, C E; Abdelgadir, S E; Resko, J A (1997) Regulation of aromatase gene expression in the adult rat brain. Brain Res Bull 44:351-7
Roselli, C E; Resko, J A (1997) Sex differences in androgen-regulated expression of cytochrome P450 aromatase in the rat brain. J Steroid Biochem Mol Biol 61:365-74
Choate, J V; Resko, J A (1996) Effects of androgen on brain and pituitary androgen receptors and LH secretion of male guinea pigs. J Steroid Biochem Mol Biol 59:315-22

Showing the most recent 10 out of 29 publications