The overall goal is to understand the mechanisms by which prolactin release, synthesis and storage are controlled.
The specific aims are: 1) To test if mechanisms controlling Ca+2-induced prolactin release fit into an overall pattern developed for Ca+2-mediated actions. This pattern is a rapid increase in cytosolic Ca+2 levels that quickly returns to basal, and sustained Ca+2 influx that does not increase cytosolic Ca+2 concentrations because efflux is also stimulated. We will see if estrogen and agents that affect cyclic AMP affect this pathway. 2) To test if proteins that are not normally packaged into secretory granules are when made in GHcells, and if the storage of these proteins is regulated as prolactin storage is. 3) To characterize proteins specifically related to secretory tissue whose synthesis is induced when prolactin storage is induced. 4) To determine if mRNAs induced in GH cells by estrogen concentrations lower than that required to induce prolactin show the same responses in normal cells and tumor cells. The techniques we will use are 45Ca++ influx, aequorin luminescence, measurements of cyclic AMP, transfection of GH cells with clones of genomic DNA, isolation of secretory granules, electron microscopy, differential hybridization and cloning into phage, and associated recombinant DNA technology.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD011487-13
Application #
3311574
Study Section
Endocrinology Study Section (END)
Project Start
1978-01-01
Project End
1991-06-30
Budget Start
1990-01-01
Budget End
1991-06-30
Support Year
13
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Yale University
Department
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520
Cui, Z J; Hidaka, H; Dannies, P S (1996) KN-62, a calcium/calmodulin-dependent protein kinase II inhibitor, inhibits high potassium-stimulated prolactin secretion and intracellular calcium increases in anterior pituitary cells. Biochim Biophys Acta 1310:343-7
Sun, Z; Li, P S; Dannies, P S et al. (1996) Properties of human prolactin (PRL) and H27A-PRL, a mutant that does not bind Zn++. Mol Endocrinol 10:265-71
Rhee, H K; Sun, Z; Kim, S S et al. (1995) Biological activity and immunological reactivity of human prolactin mutants. Endocrinology 136:4990-5
Mastro, R M; Dannies, P S (1995) Lack of correlation of distribution of prolactin (PRL) charge isoforms with induction of PRL storage. Endocrinology 136:69-74
Cui, Z J; Gorelick, F S; Dannies, P S (1994) Calcium/calmodulin-dependent protein kinase-II activation in rat pituitary cells in the presence of thyrotropin-releasing hormone and dopamine. Endocrinology 134:2245-50
Arrandale, J M; Dannies, P S (1994) Inhibition of rat prolactin (PRL) storage by coexpression of human PRL. Mol Endocrinol 8:1083-90
Cui, Z J; Dannies, P S (1992) Thyrotropin-releasing hormone-mediated Mn2+ entry in perifused rat anterior pituitary cells. Biochem J 283 ( Pt 2):507-13
Pachter, J A; Law, G J; Dannies, P S (1991) Ca2+ channel agonists enhance thyrotropin-releasing hormone-induced inositol phosphates and prolactin secretion. Eur J Pharmacol 195:373-9
Van Itallie, C M; Kieffer, L J; Carbone, R et al. (1990) Estradiol decreases retention of rhodamine 123 fluorescence in GH4C1 pituitary tumor cells. Mol Endocrinol 4:140-5
Law, G J; Pachter, J A; Thastrup, O et al. (1990) Thapsigargin, but not caffeine, blocks the ability of thyrotropin-releasing hormone to release Ca2+ from an intracellular store in GH4C1 pituitary cells. Biochem J 267:359-64

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