This application examines the role of hormone metabolizing enzymes in maintaining extra and intra-cellular hormone concentrations. These are very important in determining the biological impact of hormones in health and disease. Hormone metabolizing enzymes not only degrade hormones but in some cases convert them from an inactive to an active form. The class of hormones that are being studied are peptides and thyroid hormones. The peptide hormone that will be focused on is thyrotropin releasing hormone (TRH). TRH is not only a major regulator of thyroid function but also acts in the brain to regulate temperature, gastrointestinal function, and blood pressure regulation. Certain enzymes that degrade TRH also act on other peptides including substance P, neurotensin, and luteinizing hormone releasing hormone (LHRH). In the proposed research, modal systems will be employed to define the specific enzymes involved in hormone metabolism and, to identify drugs and other compounds that inhibit enzymes, and to quantitate the role of specific enzymes in hormone degradation. Hormone degrading enzymes and hormone concentrations are quite different during development as compared to the adult. This may be partly related to the fact that the placenta metabolizes hormones made in the thyroid (thyroid hormones) or the pancreatic islets and GI tract (TRH). Therefore the placenta as well as other tissues will be studied to determine how they affect hormone levels and how these levels affect hormone action.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK027850-09
Application #
3228513
Study Section
Endocrinology Study Section (END)
Project Start
1981-07-01
Project End
1991-08-31
Budget Start
1989-09-01
Budget End
1991-08-31
Support Year
9
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Massachusetts Medical School Worcester
Department
Type
Schools of Medicine
DUNS #
660735098
City
Worcester
State
MA
Country
United States
Zip Code
01655
Kakucska, I; Romero, L I; Clark, B D et al. (1994) Suppression of thyrotropin-releasing hormone gene expression by interleukin-1-beta in the rat: implications for nonthyroidal illness. Neuroendocrinology 59:129-37
Roti, E; Emerson, C H (1992) Clinical review 29: Postpartum thyroiditis. J Clin Endocrinol Metab 74:3-5
Emerson, C H; Cohen 3rd, J H; Young, R A et al. (1990) Gender-related differences of serum thyroxine-binding proteins in the rat. Acta Endocrinol (Copenh) 123:72-8
DeVito, W J; Allen, E; Wu, C F et al. (1989) Thyrotropin (TSH)-releasing hormone-stimulated TSH release and TSH concentration in the guinea pig pituitary, as determined by a heterologous radioimmunoassay. Endocrinology 124:1190-7
Gesundheit, N; Petrick, P A; Nissim, M et al. (1989) Thyrotropin-secreting pituitary adenomas: clinical and biochemical heterogeneity. Case reports and follow-up of nine patients. Ann Intern Med 111:827-35
Cohen 3rd, J H; Alex, S; DeVito, W J et al. (1989) Fasting-associated changes in serum thyrotropin in the rat are influenced by gender. Endocrinology 124:3025-9
Liberman, C; Nogimori, T; Wu, C F et al. (1989) TRH pharmacokinetics and nerve stimulation evoked prostatic fluid secretion during TRH infusion in the dog. Acta Endocrinol (Copenh) 120:134-42
Emerson, C H; Lew, R; Braverman, L E et al. (1989) Serum thyrotropin concentrations are more highly correlated with serum triiodothyronine concentrations than with serum thyroxine concentrations in thyroid hormone-infused thyroidectomized rats. Endocrinology 124:2415-8