Sarasin A, Schlumpf M, Müller M, Fleischmann I, Lauber ME, Lichtensteiger W. Adrenal-mediated rather than direct effects of nicotine as a basis of altered sex steroid synthesis in fetal and neonatal rat. Reprod Toxicol 17: 153-162
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.
"A3: An increasing number of pregnant women use NRT for smoking cessation;147 and in many countries, NRTs are available as over-the-counter products. Although NRT is considered to be a good smoking cessation tool in the nonpregnant population148 and may be a better alternative than continuing smoking during pregnancy, it is claimed to deliver higher concentrations of nicotine to the fetus than cigarette smoking.133 Considering that many of the harmful fetal effects of cigarette smoking attributes to nicotine, it is reasonable to hypothesize a similar effect of NRT. "
[Show abstract][Hide abstract] ABSTRACT: Maternal cigarette smoking may affect the intrauterine hormonal environment during pregnancy and this early fetal exposure may have detrimental effects on the future trajectory of reproductive health. In this review, we discuss the epidemiological literature on the association between prenatal exposure to maternal cigarette smoking and several aspects of reproductive health. The literature points towards an increased risk of the urogenital malformation cryptorchidism, but a potential protective effect on the risk of hypospadias in sons following prenatal cigarette smoking exposure. Studies on sexual maturation find a tendency towards accelerated pubertal development in exposed boys and girls. In adult life, prenatally exposed men have impaired semen quality compared with unexposed individuals, but an influence on fecundability, that is, the biological ability to reproduce, is less evident. We found no evidence to support an association between prenatal cigarette smoking exposure and testicular cancer. Among adult daughters, research is sparse and inconsistent, but exposure to cigarette smoking in utero may decrease fecundability. In conclusion, prenatal exposure to cigarette smoking may cause some long-term adverse effects on the reproductive health.
Asian Journal of Andrology 01/2014; 16(1):39-49. DOI:10.4103/1008-682X.122351 · 2.60 Impact Factor
"In subsequent studies in rats, it was shown that both nicotine and cotinine inhibited aromatase activity in the basal forebrain of male fetuses. Nicotine was twice as effective as cotinine and the effects of the two drugs were additive (Sarasin et al., 2003). Using [ 11 C]vorozole, we have recently shown that acute in vivo exposure to nicotine doses which produced plasma levels similar to those found in smokers, resulted in significant region-and dose-dependent decreases in aromatase availability in the female baboon brain. "
[Show abstract][Hide abstract] ABSTRACT: Cigarette smoking continues to be a major public health problem, and while smoking rates in men have shown some decrease over the last few decades, smoking rates among girls and young women are increasing. Practically all of the important aspects of cigarette smoking and many effects of nicotine are sexually dimorphic (reviewed by Pogun and Yararbas, 2009). Women become addicted more easily than men, while finding it harder to quit. Nicotine replacement appears to be less effective in women. This may be linked to the observation that women are more sensitive than men to non-nicotine cues or ingredients in cigarettes. The reasons for these sex differences are mostly unknown. Several lines of evidence suggest that many of the reported sex differences related to cigarette smoking may stem from the inhibitory effects of nicotine and other tobacco alkaloids on estrogen synthesis via the enzyme aromatase (cyp19a gene product). Aromatase is the last enzyme in estrogen biosynthesis, catalyzing the conversion of androgens to estrogens. This review provides a summary of experimental evidence supporting brain aromatase as a potential mediator and/or modulator of nicotine actions in the brain, contributing to sex differences in smoking behavior. Additional research on the interaction between tobacco smoke, nicotine, and aromatase may help devise new, sex specific methods for prevention and treatment of smoking addiction.
Frontiers in Pharmacology 11/2012; 3:185. DOI:10.3389/fphar.2012.00185 · 3.80 Impact Factor
"The activity of nicotine is gender-specific , since cotinine, a nicotine metabolite, is an aromatase inhibitor  that decreases oestrogen end increases testosterone levels. Polonium 210 in cigarettes  may have similar activity as other metalloestrogens [24,82]. Other carcinogens in cigarette smoke should be re-evaluated for their xenoestrogen or aromatase inhibitor potency. "
[Show abstract][Hide abstract] ABSTRACT: The role of steroids in carcinogenesis has become a major concern in environmental protection, biomonitoring, and clinical research. Although historically oestrogen has been related to development of reproductive system, research over the last decade has confirmed its crucial role in the development and homeostasis of other organ systems. As a number of anthropogenic agents are xenoestrogens, environmental health research has focused on oestrogen receptor level disturbances and of aromatase polymorphisms. Oestrogen and xenoestrogens mediate critical points in carcinogenesis by binding to oestrogen receptors, whose distribution is age-, gender-, and tissue-specific. This review brings data about cancer types whose eatiology may be found in environmental exposure to xenoestrogens. Cancer types that have been well documented in literature to be related with environmental exposure include the reproductive system, breast, lung, kidney, pancreas, and brain. The results of our data mining show (a) a significant correlation between exposure to xenoestrogens and increased, gender-related, cancer risk and (b) a need to re-evaluate agents so far defined as endocrine disruptors, as they are also key molecules in carcinogenesis. This revision may be used to further research of cancer aetiology and to improvement of related legislation. Investigation of cancers caused by xenoestrogens may elucidate yet unknown mechanisms also valuable for oncology and the development of new therapies.
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