Nicotine inhibits expression of Prrx1 in pituitary stem/progenitor cells through epigenetic regulation, leading to a delayed supply of growth-hormone-producing cells.

Growth Hormone & IGF Research : Official Journal of the Growth Hormone Research Society and the International IGF Research Society
Ayaka HibaraMasashi Higuchi

Abstract

Nicotine, a toxic component of smoking, adversely affects animal growth and reproduction by decreasing secretion of anterior pituitary hormones. However, it has not been clarified whether nicotine inhibits the supply of endocrine cells in the pituitary gland. The present study investigated short- and long-term effects of persistent nicotine exposure on the pituitary glands of young animals. Three-week-old male Wistar rats were exposed to nicotine (1 mg/kg body weight/day) for 7 days, and gene expression, cell numbers, and DNA methylation status were analyzed on the following day and 4 weeks after final treatments. The expression level of the stem cell marker Sox2 was not changed by nicotine exposure throughout the experiment. On the other hand, nicotine inhibited expression of a progenitor cell marker, Prrx1, and growth hormone (Gh). Immunohistochemical analysis showed that the SOX2-positive cells positive for PRRX1 in nicotine-treated groups decreased to 61% (4-week-old) and 70% (8-week-old) of the saline-treated controls. In addition, the proportion of GH-positive cells in nicotine-treated group was 14% lower than that of saline-treated controls. Furthermore, first intron hypermethylation of Prrx1 was detected by a bisulfite ...Continue Reading

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