Neurotensin and neurotensin receptor 1 expression in human myometrium and uterine leiomyomas.
Leiomyomas or fibroids are the most frequently diagnosed tumors of the female genital tract, and their growth seems to be steroid-hormone dependent by a yet undetermined cellular and molecular mechanism. Sexual hormones induce the secretion of growth factor peptides and the expression of their receptors, stimulating cell proliferation. One of these factors is neurotensin, and increasing evidence suggests that it can promote growth of different cancer cells. Since there are no data on neurotensin expression in normal and tumoral uterine tissue, we have analyzed the expression of NTS and NTSR1 receptor using immunohistochemistry for protein detection, in situ hybridization to detect cells expressing NTS mRNA, and RT-PCR to detect NTSR1 transcript as well as any of the alternative splice variants recently described for this receptor. We found that NTS and NTSR1 are expressed in connective cells of normal myometrium. In leiomyomas, immunoreactivity for NTS and NTSR1 receptor is colocalized in the smooth muscle cells that are also transcribing NTS. Women receiving high doses of steroids for in vitro fertilization showed tumor growth and increased immunoreactivity for neurotensin and NTSR1 receptor. Interestingly, alternative splice variants of NTSR1 receptor were detected only in tumoral tissue. These findings suggest a role of steroid hormones inducing neurotensin expression in leiomyoma smooth muscle cells. In these cells, NTS could act autocrinally through NTSR1 receptor, promoting their proliferation.
Rodríguez
Yurena
Y
Area de Biología Celular, Facultad de Medicina,Universidad de La Laguna, Tenerife, Spain.
Almeida
Teresa A
TA
Valladares
Francisco
F
Báez
Delia
D
Montes de Oca
Francisco
F
García
Candelaria
C
Dorta
Idaira
I
Hernández
Mariano
M
Reyes
Ricardo
R
Bello
Aixa R
AR
D000328:Adult; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007889:Leiomyoma / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009215:Myometrium / Q000378:metabolism*; D009496:Neurotensin / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D018028:Receptors, Neurotensin / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014594:Uterine Neoplasms / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D012334:RNA, Neoplasm; D018028:Receptors, Neurotensin; C114036:neurotensin type 1 receptor; D009496:Neurotensin