Estrous cycle influences the expression of neuronal nitric oxide synthase in the hypothalamus and limbic system of female mice

<p>Abstract</p> <p>Background</p> <p>Nitric oxide plays an important role in the regulation of male and female sexual behavior in rodents, and the expression of the nitric oxide synthase (NOS) is influenced by testosterone in the male rat, and by estrogens in the female. We have here quantitatively investigated the distribution of nNOS immunoreactive (ir) neurons in the limbic hypothalamic region of intact female mice sacrificed during different phases of estrous cycle.</p> <p>Results</p> <p>Changes were observed in the medial preoptic area (MPA) (significantly higher number in estrus) and in the arcuate nucleus (Arc) (significantly higher number in proestrus). In the ventrolateral part of the ventromedial nucleus (VMHvl) and in the bed nucleus of the stria terminalis (BST) no significant changes have been observed. In addition, by comparing males and females, we observed a stable sex dimorphism (males have a higher number of nNOS-ir cells in comparison to almost all the different phases of the estrous cycle) in the VMHvl and in the BST (when considering only the less intensely stained elements). In the MPA and in the Arc sex differences were detected only comparing some phases of the cycle.</p> <p>Conclusion</p> <p>These data demonstrate that, in mice, the expression of nNOS in some hypothalamic regions involved in the control of reproduction and characterized by a large number of estrogen receptors is under the control of gonadal hormones and may vary according to the rapid variations of hormonal levels that take place during the estrous cycle.</p

Environment and brain sexual differentiation

Several environmental substances (synthetic or natural) are able to impact endocrine function (endocrine disrupting chemicals, EDCs) and, therefore, they may have long-term consequences, especially if exposure occurs during embryonic development. Most of EDCs are agonists or antagonists of androgen or estrogen receptors, therefore they may interfere with brain and behavior sexual differentiation. We present here data collected in our laboratory on two widely used animal models: the mouse and the Japanese quail. In the quail, we investigated the effect of several EDCs [diethylstilbestrol (DES), genistein or ethylene,1,1-dichloro-2,2-bis-p-chlorophenyl (DDE)] administered in eggs on the differentiation of male sexual behavior and of the parvocellular sexually dimorphic vasotocin system. In the mouse we investigated the effects of perinatal exposure to bisphenol A (BPA) or genistein on the sexual differentiation of NO producing system and of the kisspeptin system. We investigated also the organizational effects of these EDCs on sexual, social, and explorative behaviors. Our data suggest that precocious exposure to EDCs through maternal administration (in mice) or in egg deposition (in quail) may permanently alter some sexually dimorphic circuits and influence in a gender-oriented way some behaviors. In particular, the timing of exposure to EDCs is a critical factor, such that the effects of a particular EDC will vary over the lifecycle of the animal as well as across species and phyla. Therefore, exposure to the estrogenic chemicals during embryonic development has consequences beyond impaired function of the reproductive axis. This makes it very challenging to evaluate the short and long-term effects of EDCs. These compounds are therefore, in addition to gonadal steroids and neurosteroids, a third player within the nervous system for its development and differentiation. The evolutionary implications of having them in the normal food supply for certain human populations (i.e. phytoestrogen derivatives from soy), as well as for wild and farm animals should stimulate a wide discussion about their beneficial or adverse role. Acknowledgements. The studies reported here were supported by grants from University of Torino, Regione Piemonte and Fondazione San Paolo (Neuroscience Project

Sex Hormones and Optic Nerve Disorders: A Review

Aim: This review article presents a comprehensive overview of the literature on sex hormones (estrogens, androgens, progesterone) and optic nerve disorders, with a discussion of the implications for therapy and prevention.Methods: Epidemiological, pre-clinical and clinical studies were reviewed.Results: Analysis of the biological basis for a relationship between eye diseases and sex hormones showed that some types of hormones can exert a protective effect either directly on the retina and optic nerve or indirectly by modulating ocular blood flow. For example, it seems that estrogen exposure has a protective effect against glaucoma, whereas its deficit may lead to early onset of the disease. If further studies confirm the data in the literature, estrogen therapy, because of its antioxidant action, may be effective in the treatment of Leber's hereditary optic neuropathy, whereas, in the light of current studies, there does not seem to be an influence of estrogen on non-arteritic anterior ischemic optic neuritis (NAION).Conclusions: Although there is some evidence that in some optic nerve pathologies the sex hormones seem to play an important role there are still too few studies providing evidence for its wider use in clinical practice

Effects of environment on brain sexual differentiation: role of steroids and of endocrine disruptors

Several environmental substances (synthetic or natural) are able to impact endocrine function (endocrine disrupting chemicals, EDCs) and, therefore, they may have long-term consequences, especially if exposure occurs during embryonic development. Most of EDCs are agonists or antagonists of androgen or estrogen receptors, therefore they may interfere with brain and behavior sexual differentiation. We present here data collected in our laboratory on two widely used animal models: the mouse and the Japanese quail. In the quail, we investigated the effect of several EDCs [diethylstilbestrol (DES), genistein or ethylene,1,1-dichloro-2,2-bis-p-chlorophenyl (DDE)] administered in eggs on the differentiation of male sexual behavior and of the parvocellular sexually dimorphic vasotocin system. In the mouse we investigated the effects of perinatal exposure to bisphenol A (BPA) or genistein on the sexual differentiation of NO producing system and of the kisspeptin system. We investigated also the organizational effects of these EDCs on sexual, social, and explorative behaviors. Our data suggest that precocious exposure to EDCs through maternal administration (in mice) or in egg deposition (in quail) may permanently alter some sexually dimorphic circuits and influence in a gender-oriented way some behaviors. In particular, the timing of exposure to EDCs is a critical factor, such that the effects of a particular EDC will vary over the lifecycle of the animal as well as across species and phyla. Therefore, exposure to the estrogenic chemicals during embryonic development has consequences beyond impaired function of the reproductive axis. This makes it very challenging to evaluate the short and long-term effects of EDCs. These compounds are therefore, in addition to gonadal steroids and neurosteroids, a third player within the nervous system for its development and differentiation. The evolutionary implications of having them in the normal food supply for certain human populations (i.e. phytoestrogen derivatives from soy), as well as for wild and farm animals should stimulate a wide discussion about their beneficial or adverse role. Acknowledgements. The studies reported here were supported by grants from University of Torino, Regione Piemonte and Fondazione San Paolo (Neuroscience Project