Prenatal nicotine exposure selectively affects perinatal forebrain aromatase activity and fetal adrenal function in male rats.
Previous studies have revealed effects of prenatal nicotine treatment on fetal plasma testosterone and perinatal sexual brain differentiation in the rat. In an attempt to further elucidate the processes underlying this action of nicotine, we studied the effect of the drug on brain steroid aromatase which converts androgens to estrogens and is known to be important in sexual brain differentiation. Aromatase activity (AA) was measured by the conversion of [1 beta-3H]-androstenedione to estrone in a brain region comprising preoptic, hypothalamic and amygdaloid areas. In untreated animals, the development of AA between gestational day (GD) 18 and postnatal day (PN) 15 was similar in both sexes, except for a significant drop of AA in female brain at PN6, i.e., during the later part of the critical period for sexual brain differentiation. When time-pregnant rats were treated with nicotine delivered by an osmotic minipump for either one week (2 mg/kg/d or 6 mg/kg/d from GD12) or two weeks (6 mg/kg/d from GD8), their male offspring showed a decrease of AA to female levels at PN6, the sex difference existing at this stage thus being abolished. AA of offspring from dams bearing tartaric acid-containing minipumps or sham-operated at GD8 or GD12 was identical to that of untreated controls. No drug effect was seen in female fetuses and offspring. Sex differences in the developmental effect of nicotine may thus involve brain aromatase. An additional sex-dependent effect of nicotine was observed in the male fetal adrenal axis at GD18. Whether the drug effects on the two steroid hormone systems are interrelated, remains to be elucidated.
von Ziegler
N I
NI
Institute of Pharmacology, University of Zurich, Switzerland.
Schlumpf
M
M
Lichtensteiger
W
W
D000311:Adrenal Glands / Q000187:drug effects* / Q000196:embryology; D000818:Animals; D001141:Aromatase / Q000378:metabolism*; D003345:Corticosterone / Q000097:blood; D005260:Female; D005333:Fetus / Q000187:drug effects / Q000502:physiology; D015918:Infusion Pumps, Implantable; D008297:Male; D009538:Nicotine / Q000008:administration & dosage / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D016548:Prosencephalon / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D011863:Radioimmunoassay; D051381:Rats; D015203:Reproducibility of Results; D012727:Sex Characteristics
D009538:Nicotine; D001141:Aromatase; D003345:Corticosterone