Expression of Thyrotropin-Releasing Hormone by Human Melanoma and Nevi

Abstract

Purpose: Thyrotropin-releasing hormone (TRH) is a tripeptide hormone produced by the hypothalamus in response to hypothyroidism. RNA transcripts for the TRH prohormone have recently been described in melanoma cell lines. To expand these findings, we have examined cultured melanoma cells and melanocytes, human melanoma tumors, and nevi for the expression of TRH.Experimental Design: Five melanoma cell lines were analyzed by reverse transcription-PCR/Southern blotting for preproTRH message. The same melanoma lines and two melanocyte lines were examined by immunocytochemistry for TRH protein expression and for growth response to exogenous TRH. Immunohistochemistry was used to test for TRH protein in sections of 19 melanomas, 33 dysplastic nevi, and 27 benign nevi.Results: TRH message and protein were detected in all melanoma cell lines examined. Melanocytes were also found to express TRH protein. Four of the five melanoma cell lines but neither melanocyte line responded with a increase in proliferation to low concentrations of exogenous TRH. TRH immunoreactivity was observed in 12 of 19 melanomas (63%), 23 of 33 (69.7%) dysplastic nevi, and 14 of 27 (51.9%) benign nevi. Expression in dysplastic nevi was significantly greater than in benign nevi. Upon separate analysis of nevi from melanoma patients, the difference between dysplastic and benign nevi was even more significant. However, in healthy individuals, no difference between dysplastic and benign nevi was observed. Furthermore, dysplastic nevi from melanoma patients had a significantly higher percentage of TRH-positive cells when compared with healthy individuals.Conclusions: TRH is commonly expressed by melanomas and dysplastic nevi and may function as a melanoma autocrine growth factor. The presence of TRH in dysplastic nevi may be predictive for the development of melanoma. Our findings have significant clinical and biological implications for future research into the early stages of melanoma initiation and progression.

Promotion of melanoma growth by the metabolic hormone leptin

“…The endocrine features of melanoma have been an active topic of research in our laboratory over the past several years. We have reported that melanoma cells produce thyrotropin releasing hormone (TRH) and respond to this peptide hormone by proliferation, suggesting the presence of an autocrine loop (1). We have also demonstrated the expression of functional thyroid stimulating hormone (TSH) receptors by human melanoma cells, which exhibit a proliferative response to TSH through activation of the mitogen-activated protein kinase (MAPK) pathway (2).…”

Thyrotropin releasing hormone (TRH): a new player in human hair‐growth control

“…TRH immunoreactivity (IR) has also been described in melanoma cells and in primary melanocyte cultures. Moreover, melanoma cells, but not normal melanocytes, respond to TRH stimulation in vitro with increased proliferation (18). Furthermore, it is also known that large amounts of TRH are produced in amphibian skin (19) in the epithelium lining the cutaneous glands in the epidermis (20).…”

Cutaneous Malignant Melanoma Associated with Papillary Thyroid Cancer

“…Some studies have reported that TSH is more likely to be expressed by dysplastic nevi than by benign nevi, and the dysplastic nevi of melanoma patients have a higher TSH expression than that of healthy individuals. Thus, TSH has been implicated in the malignant transformation of melanocytes to melanoma, and TSH stimulates the growth of melanoma cells 5,6 . On the other hand, the possibility has been suggested that the melanoma induces the thyroid dysfunction and this leads to hypothyroidism under the condition of low circulating thyroid hormone levels and concomitantly elevated TSH levels, although an autoimmune mechanism has also been suggested 2 .…”