The mammalian thyroid gland contains two different parenchymal cell types. One type, follicular cells are of endodermal origin and produce the hormones thyroxine and tri-iodothyronine. The second type, parafollicular cells are of neural crest origin and produce the peptide hormones, calcitonin and somatostatin as well as the biogenic amine, serotonin. The two types of parenchymal cells are contained within the basal laminae of thyroid follicles and are connected by desmosomes. We propose, as a working hypothesis, that this close spatial relationship between follicular and parafollicular cells is functionally meaningful and evolved to subserve the role of facilitating parafollicular to follicular cell communication. We further propose that the biogenic amine, serotonin, is secreted by parafollicular cells and serves as the messenger of intercellular communication. A corrollary of the overall hypothesis is that the parafollicular cells retain neuron-like properties, resemble serotonergic neurons, and function as para-neurons. Several specific aims will be tested in the proposed research. (1) What is the mechanism of serotonin storage in parafollicular cells? This will be determined by determining whether serotonin, somatostatin, calcitonin and serotonin binding protein (SBP) are all stored together in the same subcellular granules or vesicles of parafollicular cells using cell separation and fractionation methods. (2) How does serotonin accumulate in parafollicular cell granules? This will be studied (i) by examining the role of the protonmotive force hypothesis and serotonin uptake and (ii) by determining if serotonin exists as a complex with SBP within parafollicular cells under physiological conditions in vivo. (3) We will also test to determine if Ca++, the natural parafollicular cell secretogogue, or TSH, release SBP along with serotonin and calcitonin. Moreover, we will like to determine if a portion of SBP is retained on the plasma membrane of secreting parafollicular cells using electron microscope immunocytochemical methods and do secretory granule recycle. (4) We also propose to study where are the serotonin receptors on follicular cells that are responsible for serotonin's activation of these cells using radioligands and pharmacological manipulative procedures. We will also test to determine if parafollicular cell secretion produces a response in adjoining follicular cells and is this response mediated by serotonin. Knowledge of basic secretory mechanisms of parafollicular cell activity will help to enhance understanding the role of this rare cell type in thyroid physiology.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases (NIADDK)
Type
Research Project (R01)
Project #
5R01AM019743-10
Application #
3151249
Study Section
Endocrinology Study Section (END)
Project Start
1979-05-01
Project End
1989-04-30
Budget Start
1985-05-01
Budget End
1986-04-30
Support Year
10
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Columbia University (N.Y.)
Department
Type
Schools of Medicine
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10027
Cidon, S; Tamir, H; Nunez, E A et al. (1991) ATP-dependent uptake of 5-hydroxytryptamine by secretory granules isolated from thyroid parafollicular cells. J Biol Chem 266:4392-400
Nunez, E A; Pomeranz, H D; Gershon, M D et al. (1990) Distribution of laminin in the murine pituitary. Anat Rec 226:471-80
Tamir, H; Liu, K P; Payette, R F et al. (1989) Human medullary thyroid carcinoma: characterization of the serotonergic and neuronal properties of a neurectodermally derived cell line. J Neurosci 9:1199-212
Nunez, E A; Payette, R; Quimby, F (1988) Thyroid medullary carcinoma of the Djungarian hamster Phodopus sungorus. Ultrastructural evidence for the production of normal and atypical intracellular granules. Virchows Arch B Cell Pathol Incl Mol Pathol 54:284-94
Nunez, E A; Payette, R F; Tamir, H et al. (1988) Ultrastructural immunocytochemical studies of the localization and distribution of somatostatin, calcitonin, calcitonin gene-related peptide, and substance P in the bat thyroid follicle. Anat Rec 221:707-13
Barasch, J; Gershon, M D; Nunez, E A et al. (1988) Thyrotropin induces the acidification of the secretory granules of parafollicular cells by increasing the chloride conductance of the granular membrane. J Cell Biol 107:2137-47
Payette, R F; Gershon, T R; Gershon, M D et al. (1987) Occurrence of cells containing paracrystalloid material in the intestinal lamina propria of the hibernating bat Myotis lucifugus. Anat Rec 218:149-56
Barasch, J M; Mackey, H; Tamir, H et al. (1987) Induction of a neural phenotype in a serotonergic endocrine cell derived from the neural crest. J Neurosci 7:2874-83
Payette, R F; Gershon, M D; Nunez, E A (1987) Two types of secretory granules in gonadotrophs: discrimination by the simultaneous EM immunocytochemical localization of serotonin and beta-follicle stimulating hormone. Anat Rec 219:394-401
Payette, R F; Gershon, M D; Nunez, E A (1986) Colocalization of luteinizing hormone and serotonin in secretory granules of mammalian gonadotrophs. Anat Rec 215:51-8

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