Previous investigations from The Whittier Institute have demonstrated that human pituitary glands contain a glycosylated form of prolactin. This newly recognized form of prolactin contains a carbohydrate unit on asparagine 31. We have also shown that glycosylated prolactin is found in human serum and amniotic fluid and that both human pituitary cells and human decidual tissue secrete glycosylated prolactin in vitro. Since preliminary studies have shown that glycosylation of prolactin alters its biological activity, determination of the factors that affect synthesis and secretion of the glycosylated form will provide insight into the physiological role of glycosylated prolactin. The hypothesis to be tested is that the basal secretory form of prolactin is the less biologically active glycosylated form and that the more active, nonglycosylated form is released in response to specific stimuli. Using primary cultures of human pituitary cells as a model system, experiments are now proposed to investigate the effects of thyrotropin releasing hormone, bromocriptine, dopamine, estrogen, cylic AMP, and calcium on the synthesis and secretion of glycosylated prolactin by normal human pituitaries. Studies are also proposed to measure serum levels of glycosylated prolactin from normal individuals in various physiological states including women in the follicular, ovulatory, and luteal phases of their menstrual cycles, post-menopausal women, and pregnant and nursing women with physiologic hyperprolactinemia. The release of glycosylated prolactin will also be studied in normal volunteers after thyrotropin releasing hormone, arginine and L-dopa infusion. Overall, this proposal will permit the evaluation of the role of newly recognized forms of prolactin in normal physiology.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
2R01DK035679-02
Application #
3233944
Study Section
Reproductive Endocrinology Study Section (REN)
Project Start
1985-09-30
Project End
1989-08-31
Budget Start
1986-09-01
Budget End
1987-08-31
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Whittier Institute for Diabetes & Endoc
Department
Type
DUNS #
City
La Jolla
State
CA
Country
United States
Zip Code
92037
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Heffner, L J; Markoff, E; Yuan, R W et al. (1995) Glycosylated human prolactin: detection by immunoblotting of biological fluids is confounded by antisera crossreactivity with immunoglobulins. Biochem Biophys Res Commun 212:48-55
Carlson, H E; Markoff, E; Lee, D W (1992) On the nature of serum prolactin in two patients with macroprolactinemia. Fertil Steril 58:78-87
Haro, L S; Lee, D W; Singh, R N et al. (1990) Glycosylated human prolactin: alterations in glycosylation pattern modify affinity for lactogen receptor and values in prolactin radioimmunoassay. J Clin Endocrinol Metab 71:379-83
Liu, J H; Lee, D W; Markoff, E (1990) Differential release of prolactin variants in postpartum and early follicular phase women. J Clin Endocrinol Metab 71:605-10
McCoshen, J; Patalas, E; Markoff, E et al. (1990) Comparisons of glycosylated and nonglycosylated amniotic fluid prolactins in normal second- and third-trimester pregnancies. Am J Obstet Gynecol 163:81-5
Markoff, E; Beattie, G M; Hayek, A et al. (1990) Effects of prolactin and glycosylated prolactin on (pro)insulin synthesis and insulin release from cultured rat pancreatic islets. Pancreas 5:99-103
Markoff, E; Sigel, M B; Lacour, N et al. (1988) Glycosylation selectively alters the biological activity of prolactin. Endocrinology 123:1303-6
Markoff, E; Lee, D W; Hollingsworth, D R (1988) Glycosylated and nonglycosylated prolactin in serum during pregnancy. J Clin Endocrinol Metab 67:519-23
Markoff, E; Lee, D W (1987) Glycosylated prolactin is a major circulating variant in human serum. J Clin Endocrinol Metab 65:1102-6