epidermal-growth-factor and Goiter--Nodular

The activity of thymidine kinase (TK-EC 2.7.1.21)--an enzyme functioning as a part of the pyrimidine salvage pathway of DNA synthesis--is closely related to growth processes. The aim of the study was to measure TK activity in homogenates of human thyroid tissue of the following types: non-toxic nodular goiter (NTNG)--macroscopically unchanged tissue, non-toxic adenoma (NTA), and toxic adenoma (TA) (obtained from patients, who--before the surgery--had been treated with thyrostatic drugs for thyrotoxicosis). Thyroid tissue was obtained from female patients subjected to subtotal thyroidectomy at the Department of Endocrine Surgery, Medical University of Lódź. Thyroid homogenates were incubated in the presence of epidermal growth factor (EGF), used in five different concentrations (0.1 ng/ml, 1 ng/ml, 10 ng/ml, 100 ng/ml, 1000 ng/ml). TK activity was estimated by chromatographic measurements of the amount of the main reaction product--deoxythymidine monophosphate.. 1) We did not observe any significant difference between TK activity in the homogenates of the thyroid tissue collected from NTNG and NTA; TK activity was clearly higher in the homogenates of adenomatous tissue, collected from the patients with TA; 2) EGF increased TK activity in the homogenates of the macroscopically unchanged tissue, collected--during surgery--from the patients with NTNG, as well as in homogenates of thyroid tissue from NTA; 3) In case of hyperactive thyroid tissue, obtained from TA, EGF tended to increase TK activity, however, without any statistical differences. Our results confirm TK increased activity in hyperactive thyroid tissue. At the same time, the obtained data suggest a certain role of EGF in goiter formation in humans.

Topics: Adenoma, Oxyphilic; Animals; Enzyme Activation; Epidermal Growth Factor; Female; Goiter, Nodular; Humans; Thymidine Kinase; Thyroid Neoplasms

Epidermal growth factor (EGF) has widespread growth effects, and in some tissues proliferation is associated with the nuclear localization of EGF and epidermal growth factor receptor (EGFR). In the thyroid, EGF promotes growth but differs from thyrotropin (TSH) in inhibiting rather than stimulating functional parameters. We have therefore studied the occurrence and cellular distribution of EGF and EGFR in normal thyroid, in Graves' disease, where growth is mediated through the thyrotropin receptor (TSHR), and in a variety of human thyroid tumors. In the normal gland the staining was variable, but largely cytoplasmic, for both EGF and EGFR. In Graves' disease there was strong cytoplasmic staining for both EGF and EGFR, with frequent positive nuclei. Nuclear positivity for EGF and particularly for EGFR was also a feature of both follicular adenomas and follicular carcinomas. Interestingly, nuclear staining was almost absent in papillary carcinomas. These findings document for the first time the presence of nuclear EGF and EGFR in thyroid. Their predominant occurrence in tissues with increased growth (Graves' disease, follicular adenoma, and carcinoma) may indicate that nuclear EGF and EGFR play a role in growth regulation in these conditions. The absence of nuclear EGF and EGFR in papillary carcinomas would suggest that the role played by EGF in growth control differs between papillary carcinoma and follicular adenomas/carcinomas of the thyroid.

Topics: Adenoma; Carcinoma; Carcinoma, Papillary; Cell Nucleus; Epidermal Growth Factor; ErbB Receptors; Goiter, Nodular; Graves Disease; Humans; Immunohistochemistry; Reference Values; Thyroid Gland; Thyroid Neoplasms; Tissue Distribution

Epidermal growth factor (EGF) is believed to be one of the most potent growth factors for the thyroid gland.. We tested plasma EGF concentrations (radioreceptor method) in patients with non-toxic nodular goitre (NNG). Blood samples from patients with NNG were collected on the day before the surgery, during subtotal thyroidectomy (sTx)--from peripheral and thyroid veins, on the 3rd day after sTx, 3 months after sTx, and 9 months after the surgery.. Before the operation, the mean plasma EGF concentration in 50 women with NNG was significantly higher (1.16 +/- 0.69 ng/ml; mean +/- S.E.) than that in 32 control female patients subjected subsequently to other (non-thyroid) operations (0.41 +/- 0.27 ng/ml; P < 0.001), and that in 20 healthy women (0.35 +/- 0.11 ng/ml; P < 0.001), both of which groups were without goitre or had a small non-toxic diffuse goitre. The surgical treatment of NNG resulted in a significant reduction in plasma EGF 3 months after sTx (0.56 +/- 0.22 ng/ml). A further slight decrease was observed 9 months after sTx (0.44 +/- 0.14 ng/ml).. Our observations confirm the assumption that EGF may participate in the process of goitre formation in human subjects. However, the source of EGF involved in this process remains unclear. Some findings could suggest that plasma EGF, which was increased in patients with NNG, may be of non-thyroid origin; however, the majority of our observations strongly stress the significance of an intact thyroid in the preservation of an unchanged EGF value, suggesting a role of locally produced EGF in the pathogenesis of NNG.

Topics: Adult; Case-Control Studies; Epidermal Growth Factor; Female; Goiter, Nodular; Humans; Linear Models; Middle Aged; Thyroidectomy; Thyrotropin