Pii: S0361-9230(02)00925-5

نویسندگان

  • Melissa C. Garofolo
  • Frederic J. Seidler
  • Mandy M. Cousins
  • Charlotte A. Tate
  • Dan Qiao
  • Theodore A. Slotkin
چکیده

β-Adrenoceptors (βARs) control cell replication/differentiation, and during development, signaling is not subject to desensitization. We examined the effects of terbutaline, a β2AR agonist used as a tocolytic, on development in rat brain regions and peripheral tissues with high βAR concentrations. Prenatal terbutaline (gestational days 17–20) decreased cell numbers (DNA content) in the fetal brain and liver. Early postnatal exposure (PN2–5) reduced DNA synthesis in early-developing brain regions of females, with sensitization of the effect upon repeated terbutaline administration; after multiple terbutaline injections, DNA content was reduced in male cerebellum. The cerebellum was targeted later (PN11–14), exhibiting decreased DNA synthesis in both sexes; in contrast, cardiac DNA synthesis decreased after one injection but increased after the fourth daily injection. Our results suggest that excessive βAR stimulation by terbutaline alters cell development in brain regions and peripheral tissues, with the net effect depending on sex and the timing of exposure. These effects may contribute to neuropsychiatric, cognitive, cardiovascular, and metabolic abnormalities reported in the offspring of women treated with β-agonist tocolytics. © 2002 Elsevier Science Inc. All rights reserved.

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تاریخ انتشار 2002