Amine neurotransmitter levels in male and female rats through developmental periods.

Monoamines (MA) such as dopamine (DA), norepinephrine (NE), and 5-hydroxytryptamine (5-HT) are now generally regarded as widely distributed and essential endogenous mediators contributing to the integration of reproductive physiology. MA measured in the hypothalamus tissue of male and female rats aged 1 to 90 days showed its own characteristic development pattern. Significant differences were observed at 5, 15, and 90 days of age in NE mean levels and at all ages except for 3 days of age in 5-HT mean levels. In contrast, no sex differences were seen in DA mean levels.

Environmental temperature and cryptorchidism: effects on pregnenolone-sulfatase of mice testicular tissue.

This study examined the capacity of abdominal organs, such as the scrotal testis, exposed to environmental temperature to hydrolyze pregnenolone sulfate. The cryptorchid state of exposure to 34 degrees C during 14 days decreased testis weight by 38 and 23%. But the enzymatic activity (nanomoles of free steroid/testis) was significantly higher (p < .05) compared with the control. Moreover, a rise in the environmental temperature combined with cryptorchidism in mice, two conditions that induced testicular damage, has been related to the elaboration of factors capable of modifying, through paracrine mechanism, the androgen biosynthesis. The presence of this factor could lead to an increase in the hydrolysis of pregnenolone sulfate, but as for cryptorchidism or high environmental temperature exposure, when cryptorchid mice were exposed to temperatures of 34 degrees C an apparent synergism of both conditions produced a decrease of 66% in testis weight. It would appear that the steroid sulfatase is predominantly located in the interstitial epithelium. This study suggests that cryptorchidism and hyperthermia damage the tubular epithelium by different mechanisms.

Hypothalamic monoamine oxidase activity in ovariectomized rats after sexual behavior restoration.

The effect of estradiol benzoate, progesterone and a sequential treatment with both on the activity of the enzyme monoamine-oxidase (MAO) was assessed in mitochondria from hypothalami of ovariectomized rats. A differential effect on the subtypes A and B MAO was found according to the type of treatment. Estradiol benzoate administration decreased MAO activity, mainly that of MAO-A. Progesterone alone had no effect, and sequential treatment with estradiol benzoate plus progesterone restored sexual behavior and produced a significant increase of MAO-A activity, without changes in total MAO activity. Since MAO-A is an isoform of MAO that preferentially uses norepinephrine and serotonin as substrates and MAO-B acts on phenylethylamine and benzylamine as substrates, our findings suggest that the restoration of sexual behavior after the treatment with estradiol benzoate followed by progesterone may be associated with the differential effect exerted by the hormones on MAO subtypes, rather than to the simple decrease in hypothalamic monoamine concentrations as reported in the literature.

Effectiveness of calcium and magnesium on testicular sulfatase activity.

Nucleotides and calcium ions have been implicated in the regulation of biosynthesis of steroids, although the exact locus of calcium activity is not yet known. The administration of Ca2+ to Leydig cells increases testosterone production. Steroid sulfatase activity is reported to be enhanced by adenine nucleotides. In the present study the testicular sulfatase was evaluated in subcellular fractions by conversion of sulfate to free steroids in the presence or absence of Ca2+ and Mg2+ ions. The specific activity of the enzyme, which was located predominantly in submitochondrial fraction, showed a positive correlation with calcium, increasing 1.5-fold in the presence of 2.54 mM of calcium (62 nmol/h mg protein-1). In contrast, magnesium inhibited the enzymatic activity 1.79-fold in presence of 1.18 mM (23 nmoles/h mg protein-1). It would appear that testicular sulfatase is predominantly located in the mitochondria, which is recognized as one of the major sites of control of intracellular metabolism, and that its enzymatic activity could be modulated by calcium regulating the levels of potentially active androgens.

Antiestrogen U23,469 induced alterations of catecholamine levels on plasma and central nervous system.

The effect of antiestrogen U23,469 administration in vivo on the concentration of dopamine, norepinephrine and epinephrine in the plasma, cerebral cortex and hypothalamus in ovariectomized rats was investigated. Rats were treated with estradiol benzoate, progesterone and U23,469 in different doses, s.c., daily for 6 days. Control group was injected with sesame oil. Catecholamines were estimated by radioenzymatic assay. Six days of U23,469, estradiol benzoate, progesterone or its combination altered the catecholamine levels compared to the control. Dopamine decreased in plasma with progesterone and U23,469. In the cerebral cortex, progesterone and U23,469 increased significantly and in the hypothalamus all the treatments produced a decrease of catecholamines. The levels of NE were reduced with estradiol benzoate, progesterone and U23,469; there was no significant difference in the norepinephrine levels after different treatments in the cerebral cortex, but the NE levels were significantly decreased in the hypothalamus. Epinephrine showed differences related to the treatment, as in plasma, as in cerebral cortex and hypothalamus. These results suggest that antiestrogen treatment compared with the estradiol benzoate or progesterone may affect the catecholamine levels of the central nervous system and plasma and support the idea that AE could have an indirect effect on the catecholaminergic system.

Influence of progesterone and 17 alpha hydroxyprogesterone upon the BANA-hydrolytic activity of human sperm.

Our knowledge about temporal relationships between reproductive processes and defined changes in the plasmatic concentrations of 17 beta-estradiol, Follicle-stimulating hormone (FSH), Luteinizing hormone (LH) and progesterone (P) is still incomplete. Is known that in periovulatory phase the chance of fertilization increases to its maximum. The results obtained using different concentration of P have shown that at high concentration a fast liberation or/and exposure of the BANA-hydrolytic (B-H) activity is present. However, with low concentrations of P the enzymatic activity keeps a relation with the exposure time. In similar experimental conditions and using 17 alpha-hydroxyprogesterone it has been no change in the B-H activity. The results obtained in the present study suggest that the P possibly acts upon the sperm stimulating its hydrolytic activity, allowing its penetration through the zona pellucida of the ovum.

The sensitivity of rat uterus to serotonin in vitro is a late estrogenic response.

This study was designed to further characterize the sensitivity to serotonin of the isolated rat uterus. The contractile response to serotonin induced by the administration of estradiol was increased depending on the duration of estradiol-treatment, reaching the maximal contractility when ovariectomized rats were treated for 48 hours. Pretreatment with actinomycin D 1 hour before estrogen administration completely blocked estrogen-induced uterine sensitivity to serotonin. These results indicate that the sensitivity of rat uterus to serotonin in vitro induced by estradiol is a response occurring in the late phase and mediated by genomic activation. Following estradiol-administration uterine sensitivity to serotonin was similar in ovariectomized and ovariectomized-hypophysectomized rats, suggesting that in this response a pituitary factor is not required. The contractile responses to acetylcholine and oxytocin were not modified by estradiol; thus, estrogens induced specifically uterine sensitivity to serotonin. The present in vitro studies using pelanserin, a potent S2-antagonist, show that serotonin induced contractions in the rat uterus are mediated by interaction with S2-receptors, since pelanserin inhibited not-competitively the contractile response to serotonin.

Efecto de algunas aminas terciarias comunmente empleadas en la clinica sobre la motilidad y la viabilidad espermaticas. / The effect of tertiary amines of common clinical use upon the motility and viability of human spermatozoa

En busca de farmacos con posible accion contraceptiva, se valoro el efecto de cuatro aminas terciarias de amplio empleo en clinica, que son clorpromacina, imipramina haloperidol y verapamil, sobre la motilidad y la viabilidad de los espermatozoides humanos. Las concentraciones requeridas para disminuir en 50 por ciento la motilidad de los espermatozoides a los cinco minutos de incubacion fueron de 130, 120, 200 y 250 nanomolas/ml de medio de cultivo y las concentraciones requeridas para disminuir en 50 por ciento la viabilidad fueron de 170, 350, 240 y 780 nanomolas/ml para clorpromacina, impramina, haloperidol y verapamil respectivamente. La clorpromacina presento la mayor actividad espermaticida, y con el verapamil se observo una accion espermaticida cinco veces menor.Las dosis de estas aminas terciarias que se emplean en la clinica por vias oral o intramuscular y los niveles sanguineos que se obtienen son mucho mas altos que los requeridos para inhibir la motilidad y la viabilidad espermaticas. Se sugiere la posibilidad de emplear estos compuestos en sistemas de liberacion constantes en la vagina (anillos vaginales), tal vez sin efectos colaterales generales indeseables a la vez que conservan su accion contraceptiva local