Nitric oxide mediates sexual behavior in female rats.

Mani, Shailaja K.; Allen, J. M. C.; Rettori, Valéria; McCann, Samuel M.; O’Malley, Bert W.; Clark, James H.

doi:10.1073/pnas.91.14.6468

Cited by 167 publications

(109 citation statements)

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“…This androgen elicited sexual behavior is accentuated in nNOS Ϫ male mice in the presence of T where the males display excessive and inappropriate mounting behavior (12). In contrast, NO appears to facilitate female sexual behavior in rats (13), which suggests a possible sex difference in the role of NO in the control of sexual behavior.…”

Section: Discussionmentioning

confidence: 79%

“…N itric oxide (NO) synthesized by the enzyme neuronal nitric oxide synthase (nNOS) plays an important role in many brain functions. These include effects on long-term potentiation (1), gonadotropin secretion (2-10), and sexual behavior (11)(12)(13). NO functions as a neurotransmitter (2-10) and nNOS is present near gonadotropin-releasing hormone terminals (14) and in regions of the brain that appear to regulate emotional behaviors (15, 16).…”

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confidence: 99%

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Castration increases and androgens decrease nitric oxide synthase activity in the brain: Physiologic implications

Singh¹

2000

Proceedings of the National Academy of Sciences

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Sex differences in nitric oxide synthase (NOS) activity in different regions of the rat brain and effects of testosterone and dihydrotestosterone (DHT) treatment in orchidectomized animals were investigated. Regional but no sex differences in NOS activity were detected in gonadectomized animals. Orchidectomy significantly increased NOS activity in the hypothalamus, ''amygdala,'' and cerebellum but not in the cortex. In the hypothalamus, the increase in NOS activity after castration and its reversal by androgen treatment was mimicked by changes in neuronal NOS mRNA level. In contrast, androgen receptor (AR) mRNA level in the hypothalamus was slightly reduced by castration and increased by treatment with DHT. Again in the hypothalamus, the increase in NOS activity in castrated rats was accompanied by an increase in the number of neuronal NOS؉ cells determined immunohistochemically, whereas androgen treatment prevented this increase. The changes in NOS؉ neurons correlated with the changes in the number of AR؉ cells to a degree. Overlap of AR in NOS؉ cells was not present in the regions of the hypothalamus analyzed. These results indicate that testosterone or, most likely, its metabolite DHT down-regulates NOS activity, mRNA expression or stabilization, and the number of neuronal NOS؉ neurons. N itric oxide (NO) synthesized by the enzyme neuronal nitric oxide synthase (nNOS) plays an important role in many brain functions. These include effects on long-term potentiation (1), gonadotropin secretion (2-10), and sexual behavior (11)(12)(13). NO functions as a neurotransmitter (2-10) and nNOS is present near gonadotropin-releasing hormone terminals (14) and in regions of the brain that appear to regulate emotional behaviors (15, 16). Estradiol (E 2 ) up-regulates endothelial NOS in endothelial cells (17,18) and nNOS in the brain (18-21), and many of the actions of E 2 on the brain have been suggested to be through a NO-mediated mechanism (2-10, 18-22). Administration of E 2 and progesterone to ovariectomized rats leads to an increase in the luteinizing hormone surge, the magnitude of which is significantly attenuated after administration of nNOS antisense oligonucleotides into the third ventricle (22), suggesting an intermediary role of NO in modulating some actions of E 2 by up-regulating nNOS activity.However, the actions of androgens on NOS activity in the brain are not clear. Male mice with targeted disruption of the nNOS gene (nNOS Ϫ ) display a great increase in aggressive behavior and excessive and inappropriate mounting behavior (11). Because androgens also promote aggressive behavior (23, 24), facilitate mounting behavior (25, 26), and decrease gonadotropin release (27, 28), we wanted to elucidate whether the androgens, testosterone (T) and its 5␣ reduced metabolite, dihydrotestosterone (DHT), modulate nNOS activity in the brain and the potential mechanism(s) by which this may occur.Therefore, sex-related and region-specific distributions of NOS in select regions of the rat brain of both sexes were assessed as ...

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Section: Discussionmentioning

confidence: 79%

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confidence: 99%

Castration increases and androgens decrease nitric oxide synthase activity in the brain: Physiologic implications

Singh¹

2000

Proceedings of the National Academy of Sciences

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“…We hypothesized that leptin would also play a role in control of gonadotropin secretion in adult animals, and we therefore studied its effects on the release of FSH and LH from hemi-anterior pituitaries (APs) and also its possible action in releasing LHRH from medial basal hypothalamic explants in vitro. To determine if leptin is active in vivo, we used a model which we have often employed to evaluate stimulatory effects of peptides on LH release, namely the ovariectomized, estrogen-primed rat (18). We microinjected the protein into the third ventricle (3V) of conscious animals bearing implanted 3V cannulae and also catheters in the external jugular vein extending to the right atrium, so that we could remove blood samples before and after the injection of leptin and measure its effect on the concentrations of plasma FSH and LH.…”

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confidence: 99%

Role of leptin in hypothalamic–pituitary function

Kimura²,

Walczewska³

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

668

439

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A defect in the structure of the obese gene is responsible for development of obesity in the ob͞ob mouse. The product of expression of the gene is the protein hormone leptin. Leptin causes weight loss in ob͞ob and normal mice, it is secreted by adipocytes, and it is an important controller of the size of fat stores by inhibiting appetite. The ob͞ob mouse is infertile and has a pattern of gonadotropin secretion similar to that of prepubertal animals. Consequently, we hypothesized that leptin might play a role in the control of gonadotropin secretion and initiated studies on its possible acute effects on hypothalamic-pituitary function. After a preincubation period, hemi-anterior pituitaries of adult male rats were incubated with leptin for 3 hr. Leptin produced a dose-related increase in follicle-stimulating hormone (FSH) and luteinizing hormone (LH) release, which reached peaks with 10 ؊9 and 10 ؊11 M leptin, respectively. Gonadotropin release decreased at higher concentrations of leptin to values indistinguishable from that of control pituitaries. On the other hand, prolactin secretion was greatly increased in a dose-related manner but only with leptin concentrations (10 ؊7 -10 ؊5 M). Incubation with leptin of median eminence-arcuate nuclear explants from the same animals produced significant increases in LH-releasing hormone (LHRH) release only at the lowest concentrations tested (10 ؊12 -10 ؊10 M). As the leptin concentration was increased, LHRH release decreased and was significantly less than control release at the highest concentration tested (10 ؊6 M). To determine if leptin can also release gonadotropins in vivo, ovariectomized females bearing implanted third ventricle cannulae were injected with 10 g of estradiol benzoate s.c., followed 72 hr later by microinjection into the third ventricle of leptin (0.6 nmol in 5 l) or an equal volume of diluent. There was a highly significant increase in plasma LH, which peaked 10-50 min after injection of leptin. Leptin had no effect on plasma FSH concentrations, and the diluent had no effect on either plasma FSH or LH. Thus, leptin at very low concentrations stimulated LHRH release from hypothalamic explants and FSH and LH release from anterior pituitaries of adult male rats in vitro and released LH, but not FSH, in vivo. The results indicate that leptin plays an important role in controlling gonadotropin secretion by stimulatory hypothalamic and pituitary actions.

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“…Initially recognized for a primary role in the relaxation of peripheral vasculature, NO has since been implicated in the control of several activities that are at least partially mediated by the preoptic area or hypothalamus (1,3,14). Nitric oxide may influence these behaviors through release of a variety of neurotransmitters and hormonesamong them, dopamine (13).…”

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confidence: 99%