PMID- 12642147
OWN - NLM
STAT- MEDLINE
DCOM- 20031027
LR  - 20191025
IS  - 0890-6238 (Print)
IS  - 0890-6238 (Linking)
VI  - 17
IP  - 2
DP  - 2003 Mar-Apr
TI  - Adrenal-mediated rather than direct effects of nicotine as a basis of altered sex 
      steroid synthesis in fetal and neonatal rat.
PG  - 153-62
AB  - Prenatal nicotine interferes with rat sexual brain differentiation and may 
      influence human puberty. We studied effects of nicotine and cotinine on perinatal 
      steroid synthesis in offspring of time-pregnant rats. In vitro, cotinine 
      inhibited testosterone synthesis in neonatal rat testis. Both compounds inhibited 
      the brain aromatase of gestational day (GD) 19 male fetuses. Effective 
      concentrations were higher than levels in maternal plasma and fetal tissue at GD 
      19 after nicotine treatment from GD 12, even though nicotine accumulated in fetal 
      brain. In view of a dual effect of nicotine in male GD 18 fetuses, decreasing 
      plasma testosterone and increasing corticosterone [Dev Brain Res 1991;62:23-31], 
      we administered metyrapone on GD 17 to nicotine-treated dams. 11beta-Hydroxylase 
      inhibition completely reversed the nicotine-induced reduction of plasma 
      testosterone at GD 18. POMC mRNA in anterior pituitary of nicotine-exposed GD 18 
      fetuses was reduced, probably as a result of corticosterone feedback. These data 
      reveal a novel type of interaction of nicotine with the fetal gonadal axis 
      involving the adrenal.
FAU - Sarasin, Alexander
AU  - Sarasin A
AD  - Institute of Pharmacology and Toxicology, University of Zurich, 
      Winterthurerstrasse 190, CH-8057, Zurich, Switzerland.
FAU - Schlumpf, Margret
AU  - Schlumpf M
FAU - Muller, Malvina
AU  - Muller M
FAU - Fleischmann, Irene
AU  - Fleischmann I
FAU - Lauber, Markus E
AU  - Lauber ME
FAU - Lichtensteiger, Walter
AU  - Lichtensteiger W
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Reprod Toxicol
JT  - Reproductive toxicology (Elmsford, N.Y.)
JID - 8803591
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Gonadal Steroid Hormones)
RN  - 0 (Nicotinic Agonists)
RN  - 0 (RNA, Messenger)
RN  - 3XMK78S47O (Testosterone)
RN  - 4G7DS2Q64Y (Progesterone)
RN  - 66796-54-1 (Pro-Opiomelanocortin)
RN  - 6M3C89ZY6R (Nicotine)
RN  - EC 1.14.14.1 (Aromatase)
RN  - K5161X06LL (Cotinine)
RN  - W980KJ009P (Corticosterone)
RN  - YKH834O4BH (Epinephrine)
RN  - ZS9KD92H6V (Metyrapone)
SB  - IM
MH  - Adrenal Glands/*physiology
MH  - Animals
MH  - Animals, Newborn/*metabolism
MH  - Aromatase/biosynthesis
MH  - Corticosterone/biosynthesis
MH  - Cotinine/blood/pharmacology
MH  - Enzyme Inhibitors/pharmacology
MH  - Epinephrine/physiology
MH  - Female
MH  - Fetus/*metabolism
MH  - Gas Chromatography-Mass Spectrometry
MH  - Gonadal Steroid Hormones/*biosynthesis
MH  - Image Processing, Computer-Assisted
MH  - Kinetics
MH  - Male
MH  - Metyrapone/pharmacology
MH  - Nicotine/blood/*pharmacology
MH  - Nicotinic Agonists/blood/*pharmacology
MH  - Pregnancy
MH  - Pro-Opiomelanocortin/biosynthesis
MH  - Progesterone/biosynthesis
MH  - RNA, Messenger/biosynthesis
MH  - Rats
MH  - Rats, Long-Evans
MH  - Testis/drug effects/metabolism
MH  - Testosterone/biosynthesis/blood
EDAT- 2003/03/19 04:00
MHDA- 2003/10/28 05:00
CRDT- 2003/03/19 04:00
PHST- 2003/03/19 04:00 [pubmed]
PHST- 2003/10/28 05:00 [medline]
PHST- 2003/03/19 04:00 [entrez]
AID - S0890623802001193 [pii]
AID - 10.1016/s0890-6238(02)00119-3 [doi]
PST - ppublish
SO  - Reprod Toxicol. 2003 Mar-Apr;17(2):153-62. doi: 10.1016/s0890-6238(02)00119-3.