Abstract

A systematic study of the control of LH release, synthesis and pool size by the pituitary in vitro will be performed. Using the technique of continuous perfusing of isolated pituitary cells the effects of the endocrine milieu of the donor rat, GnRH, estradiol (E2) and the interaction of GnRH and E2 will be investigated. The importance of cyclic GMP on the release/synthesis of LH and its dependence on calcium ions and the redox state will be studied. The mode of action of GnRH and estradiol on LH synthesis and release with particular reference to cyclic GMP, protein synthesis and messenger RNA will be investigated. Synthesis of LH will be studied using radiolabelled aminoacids and glucosamine with immunoprecipitation, to establish the contribution of newly synthesized hormone to pool size. The effects of GnRH and estradiol on LH synthesis will also be studied. A mathematical model of the control of LH synthesis/release by the anterior pituitary will be constructed to clarify the role of these mechanisms on the control of the hypothalamic-pituitary-ovarian axis.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
3R01HD013197-06S1
Application #
3312113
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
1979-09-01
Project End
1985-11-30
Budget Start
1984-09-01
Budget End
1985-11-30
Support Year
6
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
Virginia Commonwealth University
Department
Type
Schools of Medicine
DUNS #
City
Richmond
State
VA
Country
United States
Zip Code
23298

  Publications

Thorner, M O (1999) The discovery of growth hormone-releasing hormone. J Clin Endocrinol Metab 84:4671-6
Rawlings, S R; Canny, B J; Leong, D A (1993) Pituitary adenylate cyclase-activating polypeptide regulates cytosolic Ca2+ in rat gonadotropes and somatotropes through different intracellular mechanisms. Endocrinology 132:1447-52
Canny, B J; Rawlings, S R; Leong, D A (1992) Pituitary adenylate cyclase-activating polypeptide specifically increases cytosolic calcium ion concentration in rat gonadotropes and somatotropes. Endocrinology 130:211-5
Leong, D A; Thorner, M O (1991) A potential code of luteinizing hormone-releasing hormone-induced calcium ion responses in the regulation of luteinizing hormone secretion among individual gonadotropes. J Biol Chem 266:9016-22
Leong, D A (1991) A model for intracellular calcium signaling and the coordinate regulation of hormone biosynthesis, receptors and secretion. Cell Calcium 12:255-68
Rawlings, S R; Berry, D J; Leong, D A (1991) Evidence for localized calcium mobilization and influx in single rat gonadotropes. J Biol Chem 266:22755-60
Sortino, M A; Evans, W S; Speciale, C et al. (1988) Gonadotropin-releasing hormone-stimulated phosphoinositide hydrolysis in the anterior pituitary. Modulation by protein kinase C but not by cyclic nucleotides. Neuroendocrinology 48:544-50
Ho, K Y; Thorner, M O; Krieg Jr, R J et al. (1988) Effects of gonadal steroids on somatotroph function in the rat: analysis by the reverse hemolytic plaque assay. Endocrinology 123:1405-11
Veldhuis, J D; Evans, W S; Rogol, A D et al. (1987) Actions of estradiol on discrete attributes of the luteinizing hormone pulse signal in man. Studies in postmenopausal women treated with pure estradiol. J Clin Invest 79:769-76
Ho, K Y; Evans, W S; Blizzard, R M et al. (1987) Effects of sex and age on the 24-hour profile of growth hormone secretion in man: importance of endogenous estradiol concentrations. J Clin Endocrinol Metab 64:51-8

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