Nicotine acts directly on pituitary GH3 cells to inhibit prolactin promoter activity.
We have employed the GH3 rat pituitary cell line to investigate whether nicotine can regulate prolactin (PRL) gene expression. Nicotine strongly inhibited (45%) transient expression of a construct containing the first 187 base-pairs of the rat PRL promoter cloned upstream of the chloramphenicol acetyl transferase (CAT) gene. This implies that nicotine acts directly on the GH3 cells to inhibit transcription directed by the PRL promoter. Expression of a control reporter construct containing the CAT gene under the control of the RSV promoter was not affected by exposure of the cells to nicotine, demonstrating that the effect of nicotine is promoter-specific. The inhibition by nicotine of PRL promoter activity was not blocked by hexamethonium, suggesting that this effect of nicotine may be mediated by a novel type of nicotine receptor previously described in frog pituitary cells. Nicotine was also observed to yield a concentration-dependent inhibition of the stimulation by thyrotrophin-releasing hormone (TRH) of PRL promoter activity, implying that nicotine can also interfere with hormonal regulation of the PRL gene. These results suggest that the reduced serum PRL levels that result from smoking may originate in part from decreased transcription of the PRL gene resulting from a direct effect of nicotine on pituitary PRL-secreting cells.
Coleman
D T
DT
Department of Physiology & Biophysics, Mount Sinai School of Medicine, New York, NY 10029, USA.
Bancroft
C
C
D000818:Animals; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D018738:Hexamethonium / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology*; D010902:Pituitary Gland / Q000187:drug effects* / Q000378:metabolism; D011388:Prolactin / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D051381:Rats; D011993:Recombinant Fusion Proteins; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology
D011993:Recombinant Fusion Proteins; D018738:Hexamethonium; D013973:Thyrotropin-Releasing Hormone; D009538:Nicotine; D011388:Prolactin; D015500:Chloramphenicol O-Acetyltransferase