Abstract

The mechanisms of neuroendocrine control of TSH secretion will be elucidated by studying the effects of neurotrasmitters, growth hormone, somatomedin C, thyroxine and triiodothyronine on the secretion, and biosynthesis of somatostatin and Growth Hormone Releasing Hormone (GRH) and on the rate of formation of somatostatin mRNA by liquid and in situ hybridization. Secretion will be determined in hypothalamic and cerebral cortical cells in culture, and in hypothalamic slices. Biosynthesis will be determined in these culture systems, and by intracerebral administration of amine acid precursors in intact animals undergoing changes in thyroid status, GH status, neurotransmitter agonists and antagonists, and following selective neurotoxin destruction of central serotoninergic and dopaminergic pathways. As a control for neural elements not involved in pituitary regulation, somatostatin secretion and biosynthesis will be studied in cerebral cortex and spinal cord. The possible function of VIP as a physiological regulator of prolactin secretion will be determined by study of effects of intracerebroventricular injection of anti VIP on suckling and stress induced PRL release in rats, and the possible feedback effects of PRL on VIP secretion, biosynthesis and mRNA formation will be determined in hypothalamic cells in tissue culture, and in intact animals subjected to changes in PRL secretory status. The mechanism accounting for the delayed maturation of the brain VIP systems will be determined by studying the age related changes in brain IR-VIP, and VIP mRNA, the effects of thyroid hormone on this maturation, and, in cell culture, effects of thyroid hormones, NGF, and Brain Growth Factor. To determine the role of GRH in the pathogenesis of acromegaly and idiopathic hypopituitarism by studying GH secretroy responses to GRH in patients with hypothalamic-pituitary diseases, blood and CSF levels of GRH in acromegalics, and effects of constant and intermittant injections of GRH on GH and somatostatin secretion as inferred from TSH responses to TRH.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases (NIADDK)
Type
Research Project (R01)
Project #
5R01AM016684-14
Application #
3151022
Study Section
Endocrinology Study Section (END)
Project Start
1979-07-01
Project End
1989-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
14
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
Tufts University
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code

  Publications

Arem, R; Wiener, G J; Kaplan, S G et al. (1993) Reduced tissue thyroid hormone levels in fatal illness. Metabolism 42:1102-8
Abucham, J; Reichlin, S (1991) Regulation of cholecystokinin octapeptide secretion by rat cerebral cortical cells in primary culture. Endocrinology 129:3125-31
Stern, J M; Reichlin, S (1990) Prolactin circadian rhythm persists throughout lactation in women. Neuroendocrinology 51:31-7
Abucham, J; Reichlin, S (1990) Cysteamine induces cholecystokinin release from the duodenum. Evidence for somatostatin as an inhibitory paracrine regulator of cholecystokinin secretion in the rat. Gastroenterology 99:1633-40
Hann, L E; Tatro, J B; Sullivan, D A (1989) Morphology and function of lacrimal gland acinar cells in primary culture. Invest Ophthalmol Vis Sci 30:145-58
Abucham, J; Bollinger-Gruber, J; Reichlin, S (1989) Pantethine, a somatostatin depleting agent, increases food intake in rats. Pharmacol Biochem Behav 33:585-9
Lorenzo, M J; Sanchez-Franco, F; de los Frailes, M T et al. (1989) Synthesis and secretion of vasoactive intestinal peptide by rat fetal cerebral cortical and hypothalamic cells in culture. Endocrinology 125:1983-90
Goldman, J A; Molitch, M E; Thorner, M O et al. (1987) Growth hormone and prolactin responses to bolus and sustained infusions of GRH-1-40-OH in man. J Endocrinol Invest 10:397-406
Reichlin, S (1987) Secretion of somatostatin and its physiologic function. J Lab Clin Med 109:320-6
Dawson-Hughes, B; Stern, D; Goldman, J et al. (1986) Regulation of growth hormone and somatomedin-C secretion in postmenopausal women: effect of physiological estrogen replacement. J Clin Endocrinol Metab 63:424-32

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