Coordinate gene expression of luteinizing hormone-releasing hormone (LHRH) and the LHRH-receptor after prolactin stimulation in the rat Nb2 T-cell line: implications for a role in immunomodulation and cell cycle gene expression.
PRL has been shown to induce a number of genes after the stimulation of quiescent Nb2 T-cells, including c-fos, c-myc, ornithine decarboxylase, interferon regulatory factor-1, and others. One of these genes, LHRH, has not previously been reported to respond in this manner, although we and others have reported its presence in rat and human T- and B-cells. Furthermore, recent evidence suggests that LHRH functions as an immunoregulator in a cytokine-like manner. Using the rat immature T-cell line Nb2, we present data showing for the first time that 1) the LHRH gene is regulated by PRL at various times during the cell cycle; 2) an alternatively spliced LHRH messenger RNA exists in Nb2 cells and may produce a new truncated GnRH-associated peptide (alternatively called PIF for PRL-inhibiting factor); 3) the LHRH receptor is expressed in lymphocytes in a manner similar to the LHRH gene after PRL addition, and its complementary DNA sequence is identical to that of the pituitary receptor; 5) the SH gene, found on the opposite strand of the LHRH gene, is expressed in lymphocytes at the same time and in the same manner as the LHRH gene; 6) the LHRH messenger RNA has a very short half-life in these cells; and 7) the lymphocyte LHRH transcription start site is essentially the same as the hypothalamic site. These data strengthen the relationship between PRL and LHRH expression in the immune system and further support our contention that LHRH is an important immunoregulator, on par with other known cytokines.
Wilson
T M
TM
Department of Pediatrics, Wells Center for Pediatric Research, Indianapolis, Indiana, USA.
Yu-Lee
L Y
LY
Kelley
M R
MR
D000818:Animals; D001483:Base Sequence; D002453:Cell Cycle / Q000235:genetics; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D007987:Gonadotropin-Releasing Hormone / Q000096:biosynthesis* / Q000235:genetics; D006207:Half-Life; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology; D016399:Lymphoma, T-Cell; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D015213:Neuroimmunomodulation / Q000235:genetics; D011388:Prolactin / Q000494:pharmacology*; D011389:Prolactin Release-Inhibiting Factors / Q000096:biosynthesis* / Q000235:genetics; D012326:RNA Splicing; D016372:RNA, Antisense / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011966:Receptors, LHRH / Q000096:biosynthesis* / Q000235:genetics; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D009363:Neoplasm Proteins; D016372:RNA, Antisense; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011966:Receptors, LHRH; D007987:Gonadotropin-Releasing Hormone; D011388:Prolactin; D011389:Prolactin Release-Inhibiting Factors