Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.6.99.1 (NADPH-diaphorase)
 3,903 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nitric oxide (NO) may function as an intercellular messenger in the hypothalamus and may play a role in the control of gonadotropin-releasing hormone (GnRH) secretion and sexual behavior. Progesterone also plays an important role in the regulation of reproductive functions. Recent experiments have shown that progesterone-induced sexual behavior in ovariectomized, estrogen-primed rats was caused by the release of NO from nitric oxide synthase (NOS)-containing neurons and the subsequent stimulation of the release of GnRH. To provide further neuroanatomical support for the role of NO in these gonadal steroid-dependent behavioral and physiological processes, we determined (1) the distribution of the nicotinamide-adenosine-dinucleotide phosphate-diaphorase (NADPHd) and NOS enzymes in the guinea pig preoptic area and hypothalamus, regions that contain steroid receptors; (2) the effect of estrogen on NADPHd activity in these regions; and (3) the neuroanatomical relationship between NOS and the progesterone receptor (PR). For this purpose, single-(NADPHd) and double- (NADPHd with NOS or NADPHd with PR or NOS with PR) staining techniques were applied to sections of brains of guinea pigs. The studies showed scattered NADPHd-positive neurons in most parts of the preoptic area and heavily stained cells in the hypothalamus. In these regions, the pattern and density of NOS immunoreactivity closely corresponded to the pattern of NADPHd staining. Quantitative analysis showed an increase in the number of NADPHd-positive neurons in the ventrolateral nucleus of ovariectomized animals primed with estradiol. Approximately 16% of the NOS-immunoreactive (IR) cells in the rostral preoptic area and 55% of NOS-IR cells in the ventrolateral nucleus displayed PR immunoreactivity. These results suggest that NOS may be regulated by gonadal steroids and provide neuroanatomical evidence that progesterone may exert its effect directly on more than half of NOS-synthesizing cells in the ventrolateral nucleus, a key region in the control of sexual behavior.
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PMID:Nitric oxide synthase in the guinea pig preoptic area and hypothalamus: distribution, effect of estrogen, and colocalization with progesterone receptor. 1021 92

Using nicotinamide-adenine-dinucleotide-phosphate-diaphorase (NADPHd) histochemistry, we analyzed the effects of an intracerebroventricular injection of colchicine on the activity of neuronal nitric oxide synthase in the hypothalamic nuclei of intact and ovariectomized estradiol-primed guinea pigs. We also examined the effects of colchicine on the immunocytochemical colocalization of nitric oxide synthase with the progesterone receptor in the ventrolateral nucleus, a key region in the control of sexual behavior. Treatment with colchicine resulted in a significant increase in the number of NADPHd-positive neurons in the ventrolateral nucleus in intact as well as in ovariectomized estradiol-primed animals, whereas in the other hypothalamic regions analyzed (preoptic area, paraventricular nucleus and posterior arcuate nucleus), the enzymatic activity remained unchanged. Quantitative analysis showed a significantly greater number of NADPHd-positive cells in the medial and the posterior aspects of the ventrolateral nucleus of colchicine-treated guinea pigs compared to the control group. In the caudal subdivision of this nucleus, colchicine induced nitric oxide synthase in the target cells for progesterone. These results suggest that neuronal nitric oxide synthase activity in the hypothalamus is affected by colchicine in a region-specific manner and especially in the ventrolateral nucleus, which is involved in progesterone-facilitated lordosis.
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PMID:Differential effects of colchicine on the induction of nitric oxide synthase in neurons containing progesterone receptors of the guinea pig hypothalamus. 1092 24

The evolution of neuroendocrine mechanisms governing sex-typical behaviour is poorly understood. An outstanding animal model is the whiptail lizard (Cnemidophorus) because both the ancestral and descendent species still exist. The ancestral little striped whiptail, Cnemidophorus inornatus, consists of males and females, which exhibit sex-specific mating behaviours. The descendent desert grassland whiptail, Cnemidophorus uniparens, consists only of females that alternately exhibit both female-like and male-like pseudosexual behaviour. Castrated male C. inornatus will mount a conspecific in response to exogenous androgen, although some are also sensitive to progesterone. This polymorphism in progesterone sensitivity in the ancestral species may have been involved in evolution of progesterone-mediated male-typical behaviour in the descendant unisexual lizards. We tested whether progesterone activates a typically androgenic signalling pathway by investigating hormonal regulation of neuronal nitric oxide synthase (nNOS) using in situ hybridisation and NADPH diaphorase histochemistry, a stain for nNOS protein. NADPH diaphorase is widely distributed throughout the brain of both species, although only in the periventricular nucleus of the preoptic area (pvPOA) are there differences between mounting and non-mounting individuals. The number of cells expressing nNOS mRNA and NADPH diaphorase is higher in the pvPOA of individuals that mount in response to progesterone or androgen. Furthermore, the nNOS promoter has both androgen and progesterone response elements, and NADPH diaphorase colocalises with the progesterone receptor in the pvPOA. These data suggest that a polymorphism in progesterone sensitivity in the sexual ancestor reflects a differential regulation of nNOS and may account for the male-typical behaviour in unisexual whiptail lizards.
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PMID:Neuronal nitric oxide synthase as a substrate for the evolution of pseudosexual behaviour in a parthenogenetic whiptail lizard. 2112 73