motilin and Thyroid-Neoplasms

Motilin, an important endocrine regulator of gastrointestinal motility, was once considered to be produced in the gastrointestinal tract and brain. In recent years, however, motilin has been found in the human thyroid, as well as in that of the guinea pig. The physiological function and central modulation of thyroidal motilin remain poorly understood. To determine the functional role of thyroidal motilin, we observed the concentration of motilin in the plasma and also gastric motility before and after thyroidectomy. Our studies show that both the concentration of plasma motilin and gastric motility were decreased after thyroidectomy. To explore modulation-related nuclei, a c-Fos immune response experiment was carried out. The PVN of the hypothalamus was the main area of reactivity after thyroidectomy. Subsequently, we studied the effects of electrical excitation and PVN lesions on gastric motility and the expression of motilin in the thyroid and plasma. Excitation of the PVN was shown to prompt gastric motility that was partly prevented by the motilin receptor antagonist, GM-109. The effects of PVN excitation on gastric contraction were significantly reduced in thyroidectomised rats. In addition, the expression of motilin in the thyroid was significantly increased after PVN excitation and decreased after PVN lesions. The changes in the concentration of motilin in plasma induced by PVN stimulation were positively correlated with changes of gastric motility. In our in vitro study, the motilin secreted from TT cells (a parafollicular cell line originating from human thyroid medullary carcinoma) gradually increased on day 6 of culture, and motilin and calcitonin (CT) were co-expressed in TT cells. These results demonstrate that motilin from the thyroid could be secreted into the peripheral plasma and affect gastric motility and that PVN was a central nucleus for modulating gastric motility and motilin expression in the thyroid.

Topics: Animals; Cells, Cultured; Female; Gastrointestinal Motility; Humans; Male; Motilin; Paraventricular Hypothalamic Nucleus; Proto-Oncogene Proteins c-fos; Random Allocation; Rats; Rats, Wistar; Thyroid Gland; Thyroid Neoplasms; Thyroidectomy; Thyroxine; Triiodothyronine

To investigate the expression of motilin and its precursor mRNA in normal human thyroid. To compare the expression differences of motilin and it precursor mRNA between normal thyroid and intestines. To study the expression of motilin and its precursor mRNA in human thyroid tumors and their clinical implications.. RT-PCR, Southern blot and molecular cloning were used to detect motilin transcript expression in human thyroid and mucous membrane of small intestine. Real-time PCR and immunohistochemical techniques were used to quantify motilin precursor mRNA and motilin peptide in thyroid tissue samples including adenoma, medullary carcinoma, follicular carcinoma, papillary carcinoma and nodular goiter.. (1) The expression of motilin and its precursor mRNA in normal human thyroid was primarily in the thyroid C cells. (2) RT-PCR and Southern blot showed that motilin mRNA expressed in human thyroid was identical to that expressed in duodenum with identical sequence deposited in NCBI Genbank of America. (3) Immunohistochemistry, Western blot research and real-time PCR studies showed that motilin and its precursor mRNA were expressed in normal and tumor tissues of human thyroid. Thyroid tumors (acidophilic adenoma, medullary carcinoma, follicular carcinoma, papillary carcinoma and nodular goiter) showed intense and diffuse immunostaining for motilin peptide. Moreover, the expression of motilin and its precursor mRNA in thyroid medullar carcinoma and acidophilic adenoma were significantly higher than those of normal thyroid tissue (P < 0.05). The expression in thyroid follicular and papillary carcinomas were significantly lower than those of normal thyroid tissue (P < 0.05). There was no difference of the expression between nodular goiter and normal thyroid tissue (P > 0.05).. Motilin peptide and its precursor mRNA are expressed in C cells of human thyroid. The sequence of motilin is identical to that expressed in duodenum from NCBI Genbank of America. The expressions of both motilin and its precursor mRNA in thyroid medullary carcinoma and acidophilic adenoma are significantly increased. In contrast, their expressions in thyroid follicular and papillary carcinomas are significantly decreased. Motilin may regulate physiological functions of the thyroid through parafollicular cells. Motilin may be involved in the pathogenesis of medullary carcinoma and acidophilic adenoma of the thyroid.

Topics: Adenocarcinoma, Follicular; Adult; Aged; Biomarkers, Tumor; Carcinoma, Medullary; Carcinoma, Papillary; Female; Humans; Intestinal Mucosa; Male; Middle Aged; Motilin; Nervous System Neoplasms; RNA Precursors; RNA, Messenger; Thyroid Gland; Thyroid Neoplasms