Hormone mediated changes in monoamine stores and regulation of enzymes of biosynthesis and metabolism in the rat adrenal gland. Influence of progesterone, estradiol, ACTH and testosterone administration

The influence of daily injections, for 7 days, of 17-hydroxyprogesterone caproate (8 mg/100 g body weight pro die), of estradiol-17 beta 17-undecylate (1.2 mg/100 g body weight pro die) of testosterone enanthate (2 mg/100 g body weight pro die) and of ACTH (4 IU/100 g body weight pro die) to male Wistar rats, weighing 200 g, were investigated. Monamine storage and regulation of enzymes phenylethanolamine N-methyl transferase (PNMT), monoamine oxidase (MAO) and catechol-O-methyl transferase (COMT) were studied in the adrenal glands. Results from testosterone treated rats were especially significant : the hormone administration decreased the stores of dopamine and norepinephrine (epinephrine precursors), stimulated PNMT and decreased metabolism of epinephrine by MAO and COMT. However, the adrenal content of epinephrine remained in the normal range. These findings suggest that uptake of epinephrine is accelerated in peripheral tissues by testosterone.     

Developmental profiles of catecholaminergic enzymes in adrenals of perinatal rats: effect of a hypoxic environment

Fetal and early neonatal development of adrenal catecholaminergic enzymes was studied in rats maintained under normal (normoxic) and high-altitude, 3800 m, 13% PO2 (hypoxic) conditions. In adrenals of normoxic fetuses, tyrosinehydroxylase (TH), DOPA-decarboxylase (DDC), phenylethanolamine-N-methyltransferase (PNMT), catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO) showed rapid increases in activity from day 19 to day 21 of gestation. The activities of all enzymes but TH were higher at day 1 postpartum compared to fetal values: TH was equiactive just before and after birth. In animals conceived, born and raised at high altitude, several changes indicative of impaired adrenal development occurred. The activities of the synthesizing enzymes, TH, DDC and PNMT, were variably affected at some time during the perinatal period. The activities of the catabolizing enzymes, MAO and COMT, at high altitude were increased on the last days of gestation but depressed after birth, compared to control levels. Catecholamine content in high-altitude adrenals was altered on day 19 of gestation when epinephrine was lower, and again on day 1 postpartum when both norepinephrine and epinephrine were higher than in control adrenals at sea level. Normal developmental changes and high-altitude-induced disturbances in adrenal catecholaminergic enzymes are discussed with reference to differences observed in adrenal cortical function between sea-level and high-altitude animals.     

Effects of estrogens and progesterone on the catecholaminergic activity of the adrenal medulla in female rats

Some reports in the literature allow to suspect the existence of an effect of sexual steroids on the adrenal catecholamines. To test this possibility, we have examined the catecholaminergic activity in the adrenal medulla of normal cycling rats in three phases of estrous cycle and of ovariectomized (OVX) rats injected with pharmacological doses of estradiol (ES), 2-hydroxyestradiol (HE) and/or progesterone (P). Adrenomedullary content of norepinephrine (NE) was similar during the estrous cycle, while epinephrine (E) content was increased during diestrous. This increase was concomitant with an increased phenylethanolamine-N-methyltransferase (PNMT) activity. Moreover, the monoamine oxidase (MAO) activity was significantly increased during proestrous, while the catechol-O-methyltransferase (COMT) activity was significantly decreased during estrous. In addition to these observations, ovariectomy caused a significant reduction of the E/NE ratio and of COMT and MAO activities. Administration of ES to OVX rats increased the E content, the E/NE ratio and the COMT activity as compared to vehicle-treated OVX rats. Administration of P to OVX animals led also to a significant increase of the E/NE ratio and of the COMT activity but not of the E content, while the administration of this steroid to OVX rats previously treated with ES only increased the COMT activity. Finally, administration of HE caused non-significant changes in NE and E contents and in MAO, COMT and PNMT activities. We can conclude that sexual steroids seem to be able to modify the catecholamine metabolism in the adrenal medulla and, hence, they could alter the ability of this gland to store and release these amines.     

Effect of steroid hormones on serotonin,norepinephrine and epinephrine contents in the pineal-paraphyseal complex of the soft-shelled turtle (Lissemys punctata punctata)

Summary Steroids (testosterone, oestrogen, progesterone, corticosterone, dexamethasone and deoxycorticosterone) were administered intramuscularly (0.1 mg · 100 g bw^-1) on seven consecutive days to juvenile male soft-shelled turtles. Serotonin, norepinephrine and epinephrine contents of the pineal-paraphyseal complex were measured spectrofluorometrically 24 h after the last injection. Testosterone and oestrogen decreased serotonin, norepinephrine and epinephrine levels. Progesterone treatment resulted in an increase of serotonin level and a fall in norepinephrine and epinephrine levels. Corticosterone treatment caused an increase of serotonin level and a decrease of norepinephrine and epinephrine levels. Dexamethasone failed to alter serotonin content, increased norepinephrine and decreased epinephrine levels. Deoxycorticosterone decreased serotonin and elevated epinephrine content.Abbreviations 5-HIAA 5-hydroxyindole-acetic acid - 5-MTOH 5-methoxytryptophol - ANOVA analysis of variance; bw body weight - COMT catecholamine-o-methyl transferase - E epinephrine - HIOMT hydroxyindole-o-methyl transferase - MAO monoamine oxidase - MS mean sum of squares - NAT N-acetyltransferase - NE norepinephrine - SR synaptic ribbon - SS sum of squares - SV source of variation     

The effects of soman in vitro on catechol-O-methyltransferase and monoamine oxidase activities in rabbit tissues

Soman (pinacolyl methylphosphonofluoridate) not only increases acetylcholine levels by inhibiting cholinesterases, it also alters the levels of some other neurotransmitters including norepinephrine, dopamine, and serotonin. Soman also causes an alteration in the activities of the enzymes metabolizing norepinephrine when it is administered to animals. Because these alterations may result from indirect effects on the enzymes, the effects of in vitro application of soman on catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO) activities in rabbit tissues were investigated. Enzyme activities were determined in rabbit lung, liver, cerebellum, cerebrum, brain stem, mesenteric artery, pulmonary artery, renal artery, central ear artery, thoracic aorta, and diaphragm. MAO and COMT activities were not affected by soman in any tissues tested, except the lung and liver, where the activity of COMT was increased (p less than 0.05). Thus, reported effects of soman in vivo on norepinephrine, dopamine, or serotonin concentrations, and MAO and COMT activities do not seem to result from direct effects on the activities of these amine-metabolizing enzymes.     

THE EFFECTS OF METOPIRONE AND ADRENALECTOMY ON THE REGULATION OF THE ENZYMES MONOAMINE OXIDASE AND CATECHOL-O-METHYL TRANSFERASE IN DIFFERENT BRAIN REGIONS

Abstract— The role of glucocorticoids in the regulation of the enzymes monoamine oxidase (MAO) and catechol- O -methyltransferase (COMT) in brain regions has been studied. Glucocorticoids were blocked by Metopirone. The activities of MAO and COMT were determined in the hypophysis, hypothalamus, pineal gland and in the rest of brain. All the cerebral tissues except the pineal gland demonstrated highest MAO activity 8 h after Metopirone administration, when glucocorticoids were at the lowest level. Prolonged treatment for 10 days significantly augmented MAO activity in brain, hypophysis and hypothalamus, and COMT in the hypophysis increased by 56 per cent. The COMT activity in the rest of the brain did not change significantly with either short or prolonged administration. Complete ablation of the adrenal cortex resulted in a 167 per cent rise in MAO activity of the hypophysis. Metopirone and hydrocortisone inhibit MAO and COMT in vitro. The results suggest that glucocorticoids in the circulation of normal animals inhibit the activities of MAO and COMT. The inhibition or ablation of these hormones removes this rate-limiting control of catecholamine degradation resulting in higher activities of MAO and COMT. Metopirone, an inhibitor of MAO and COMT in vitro , acts in the opposite direction in vivo due to its inhibitory effects on corticoid biosynthesis.     

Relationship Between Catechol-O-Methyltransferase and Phenolsulfotransferase in the Metabolism of Dopamine in the Rat Brain

The relationship between phenolsulfotransferase (PST) and catechol-O-methyltransferase (COMT) in the metabolism of free 3,4-dihydroxyphenylethylamine (DA, dopamine) in the rat brain was studied. In rats not pretreated with a monoamine oxidase (MAO) inhibitor a huge increase of free DA in the brain, following an intraperitoneal injection of L-3,4-dihydroxyphenylalanine (L-DOPA) or an intraventricular injection of free DA, did not lead to any noticeable change in DA sulfate or 3-methoxytyramine (3-MT), which remained undetectable by the present HPLC method. However, in rats previously treated with the MAO inhibitors pargyline or tranylcypromine, the same L-DOPA or free DA treatment resulted in significant increases in both 3-MT and DA sulfate in the hypothalamus, brainstem, and striatum. This response of COMT and PST was not affected by prior treatment of the rats with 6-hydroxydopamine, which suggests that O-methylation and sulfoconjugation occur outside adrenergic neurons not destroyed by the neurotoxin. Inhibition of COMT activity did not lead to any increase in DA sulfate, which showed that despite their common mode of action (both enzymes react preferentially at the same hydroxyl group in the DA molecule), the two enzymes are not competitive. After MAO inhibition there were strong correlations between an increase in DA sulfate and 3-MT on the one hand, and between free DA and 3-MT on the other. Because 3-MT is a marker of central DA release, these data suggest that inhibition of MAO activity not only affects DA metabolism by this enzyme but also influences DA release in the rat brain.     

Influence of cold exposure and thyroid hormones on regulation of adrenal catecholamines.

Since thyroid hormones influence urinary excretion of catecholamines after exposure to cold, the effects of hyper- and hypo-thyroidism on adrenal tyrosine hydroxylase (TH) (EC 1.14.16.2), phenylethanolamine-N-methyl transferase (PNMT) (EC 2.1.1.28), and serum dopamine-beta-hydroxylase (DbetaH) (EC 1.14.17.1) of rats of 23 and 4 degrees C were studied. TH changes resembled the urinary excretion pattern at 4 degrees C in being higher after 8 days than after 1 day of exposure, and in declining as acclimation occurred. At 23 degrees C, TH activity of hypothyroid rats was significantly higher than in euthyroid or hyperthyroid animals, and after 1 day at 4 degrees C the value increased even more. While in the hypothyroid animals at 4 degrees C the concentration of adrenal catecholamines was less, the epinephrine to norepinephrine ratio was higher than at 23 degrees C. Very high TH activity with a decline in catecholamine concentration suggests that the capacity of TH had been exceeded. PNMT activity was significantly elevated in this group. TH activity was not decreased in the hyperthyroid group at 23 degrees C, and was increased after 8 days at 4 degrees C, suggesting that circulating thyroid hormones have no direct inhibitory effect on TH. Serum DbetaH was elevated after exposure to 4 degrees C, regardless of thyroid hormonal status. The activation of adrenal TH in hypothyroid rats at 23 degrees C and of TH, PNMT, and serum DbetaH at 4 degrees C is probably the result of increased activity of the sympathetic nervous system.     

Effect of vasopressin on the induction of adrenal tyrosine hydroxylase and phenylethanolamine N-methyltransferase

We have assessed the effect of arginine vasopressin (AVP) on adrenal tyrosine hydroxylase (TH) and phenylethanolamine N-methyltransferase (PNMT) activities. Both enzymes show marked increases after systemic administration of AVP in the range of 66 and 100 micrograms/day. To determine whether the pituitary gland plays a role in these inductions, the effect of AVP (66 micrograms per day, given divided into 3 doses for 4 days) on the adrenal enzymes was studied in hypophysectomized rats. These animals showed induction of TH but not PNMT. This indicates that a pituitary factor(s) mediates the increase in PNMT caused by AVP. Adrenal TH activity was measured after the injection of AVP (1 or 2 micrograms per rat) into the lateral ventricle: there was a statistically significant increase in TH. TH was not induced in the denervated adrenal gland of rats administered AVP systemically. These findings suggest that AVP may act centrally to induce the enzyme. The continuous s.c. infusion of AVP by osmotic minipump at the rate of 1 microgram/day for 6 days led to a striking increase in adrenal TH activity. However, PNMT did not increase significantly. It can be concluded that different mechanisms are involved in the induction of adrenal TH and PNMT caused by AVP. A neural mechanism is involved in TH induction, whereas PNMT induction requires release of a pituitary factor, presumably ACTH, but innervation of the adrenal is not needed for it. Moreover, the inductions of these two enzymes are differentially sensitive to the concentration of circulating AVP.     

Metabolism of biogenic amines in neuroblastoma and glioma cells in culture

The kinetic parameters of monoamine oxidase (MAO; E.C 1.4.3.4) and catechol-O-methyltransferase (COMT; EC 2.1.1.6) were evaluated in extracts of adrenergic and non-adrenergic mouse neuroblastoma cells and in rat glioma cells. Using the naturally-occurring substrates tyramine, tryptamine, serotonin and norepinephrine, the affinity of MAO for a given substrate was independent of the presence of the catecholaminergic pathway or cell type used, with apparent Km values ranging from 8-14 microM for tryptamine to 510-580 microM for norepinephrine. The MAO activity in glioma cells was substantially greater than in either neuroblastoma clone, but Vmax values varied little with substrate among cell lines. Both the neuronal and glial COMT had a similar Km for 1-norepinephrine (200 microM); the corresponding Vmax values were also similar among the different cell lines, but represented only 2-10% of the maximal MAO activity. Neuroblastoma and glioma cells, when grown from early logarithmic to stationary phase, showed no significant changes in specific activity of either MAO or COMT. Growth of cells for 3 days with 1 mM-N6,O2'-dibutyryl adenosine-3',5'-cyclic monophosphate resulted in no marked change in either MAO or COMT activity. These results suggest that in neurons neither MAO nor COMT plays a major role in the type of transmitter inactivation that is analogous to that of acetylcholinesterase in cholinergic synapses. The occurrence of considerable MAO and acetylcholinesterase activities in glioma cells may indicate a role for these cells in neurotransmitter inactivation.     

EFFECTS OF PRE- OR POSTNATAL DEXAMETHASONE, ADRENOCORTICOTROPHIC HORMONE AND ENVIRONMENTAL STRESS ON PHENYLETHANOLAMINE N-METHYLTRANSFERASE ACTIVITY AND CATECHOLAMINES IN SYMPATHETIC GANGLIA OF NEONATAL RATS

Abstract— Injections of dexamethasone (0.1 mg/kg/day, s.c.) on the first 2–3 days of life increased the phenylethanolamine- N -methyltransferase (PNMT) activity and epinephrine content of the superior cervical ganglion (SCG) and stellate ganglion of neonatal rats; the dopamine content was unaltered while norepinephrine was slightly reduced in these ganglia. Dexamethasone did not alter the PNMT activity or epinephrine content of the salivary glands or heart. The PNMT activity and epinephrine content of the SCG remained elevated for 10–14 days. Pretreatment with 6-hydroxydopamine did not alter the dexamethasone effects.
Injections of adrenocorticotrophic hormone (ACTH) (25 munits/rat twice a day) or exposure to a cold stress (4°C, 3 times a day) on the first 2–3 days of life, elevated the plasma concentration of corticosterone, and also increased the PNMT activity and epinephrine content in SCG of neonatal rats. Injecting pregnant rats with dexamethasone or ACTH, or exposing them to cold or restraint stress on the last 3 days of gestation increased the PNMT activity and epinephrine content in the SCG of their pups. These results indicate that the actions of dexamethasone on neonatal sympathetic ganglia may be mimicked by increasing the plasma concentration of endogenous adrenocortical steroids.     

Expression of phenylethanolamine N-methyltransferase in rat sympathetic ganglia and extra-adrenal chromaffin tissue

To determine whether similar mechanisms regulate adrenergic phenotypic expression in different cellular populations, the superior cervical sympathetic ganglion (SCG) and extra-adrenal chromaffin tissue were studied in the fetal and neonatal rat; results were compared to those previously obtained with the adrenal medulla. Phenylethanolamine N-methyltransferase (PNMT), the enzyme which converts norepinephrine to epinephrine, was used as an index of adrenergic expression. PNMT catalytic activity was initially detectable in the SCG of normal, untreated fetuses at 17.0 days of gestation (E17.0), and increased three- to fourfold until postnatal day 2. Thereafter activity decreased precipitously, and was undetectable 2 weeks after birth. Immunohistochemical studies, using specific antisera to PNMT, were employed to localize the enzyme. Immunoreactivity (PNMT-IR) was undetectable in sympathetic ganglia of control animals, suggesting that this method is less sensitive than the catalytic assay. Following glucocorticoid treatment, cells heavily stained for PNMT-IR were observed in paravertebral sympathetic ganglia, including the SCG, and in the organ of Zuckerkandl. In the SCG, PNMT-IR was present in small cells presumed to be small, intensely fluorescent (SIF) cells and was never observed in principal ganglion neurons. The increase in PNMT-IR after steroid treatment was strikingly age dependent: initiation of treatment at progressively older ages during the first week of life resulted in fewer and fewer PNMT-IR cells. No response was apparent after 1 week. Moreover, treatment of pregnant rats was associated with appearance of PNMT-IR at E18.5, but not at E16.5. After treatment from days 0 to 6 of life, PNMT-IR gradually disappeared. However, retreatment on days 24–30 caused the reappearance of PNMT-IR, suggesting that exposure to steroids at birth causes (a) an immediate increase in PNMT-IR and (b) responsiveness to steroids during adulthood. Consequently, the disappearance of PNMT-IR after exposure to steroids at birth, is not simply due to death of SIF cells. We conclude that proximity to the adrenal cortex is not necessary for initial expression of PNMT. More generally, the expression of PNMT by ganglion SIF cells parallels that in adrenal chromaffin cells since initial expression was not dependent on high local concentrations of glucocorticoids, whereas subsequent development did require high levels of the hormones. Our observations suggest that similar mechanisms regulate expression and development of the adrenergic phenotype in adrenal and sympathetic ganglia.     

Inheritance of Adrenal Phenylethanolamine N-Methyltransferase Activity in the Rat

Phenylethanolamine N-methyltransferase (PNMT) is the enzyme that catalyzes the S-adenosyl-L-methionine-dependent methylation of (-)norepinephrine to (-)epinephrine in the adrenal medulla. Adrenal PNMT activity is markedly different in two highly inbred rat strains; enzyme activity in the F344 strain is more than fivefold greater than that in the Buf strain. Initial characterization of the enzyme in the two inbred strains reveals evidence for catalytic and structural differences, as reflected in dissimilar Km values for the cosubstrate (S-adenosyl-L-methionine) and prominent differences in thermal inactivation curves. To assess adrenal PNMT activity in an F344 X Buf pedigree, we employed a statistical procedure to test for one- and two-locus hypotheses in the presence of within-class correlations due to cage or litter effects. The PNMT data in the pedigree are best accounted for by segregation at a simple major locus superimposed upon a polygenic background; data obtained from the biochemical studies suggest that the major locus is a structural gene locus.     

Cytochemistry and ultrastructure of the prenatal porcine adrenal medulla

The ultrastructure and cytochemistry of fetal porcine adrenal medullae have been studied at 60, 80, and 100 days of gestation. Adrenal medullae from fetuses at 60 days of pregnancy consisted of norepinephrine cells only. Some cells containing chromaffin granules were seen in the process of mitosis. A few epinephrine cells were present in the outer medullary zone at 80 days at pregnancy, their number increasing by the 100 day of pregnancy. Chromaffin cells containing both norepinephrine and epinephrine storing granules were also present at 80 and 100 days of gestation. Norepinephrine and epinephrine specific granular vesicles in the fetal adrenal medullary cells were smaller than those reported for the adult pig. The general ultrastructural characteristics of the porcine fetal adrenal medulla were similar to those reported for prenatal adrenal medulla of other species.     

Circadian Fluctuation of Catecholamines in the Cockroach Brain-Subesophageal Ganglion Complex detected by HPLC-ECD

Fluctuations of catecholamine contents in the cockroach brain-subesophageal ganglion (Br-SG) complex were examined by HPLC with electrochemical detector. The chromatographic system detected dopamine (DA), norepinephrine (NE), epinephrine (EP) and some putative metabolites as standard compounds. Da, NE and EP were detected in the Br-SG complex whereas those metabolites such as 2,5-dihydroxyphenylacetic acid (DOPAC) and 3-methoxy 4-hydroxy phenylglycol (MOPEG) were not detected from the tissue samples in a significant amount. The distribution of DA in the central nervous system was strongly biased toward cephalic ganglia, whereas EP was distributed more evenly over all ganglia. EP existed in both free and conjugated forms, the latter being predominant. Fluctuation patterns of these catecholamines were distinct; DA level kept constant throughout the day, at ca 200 ng/mg protein, NE showed a peak around AZT (artificial Zeitgeber time) 12, i.e., the light-off moment and the rhythm free-ran in constant darkness (DD), and both the free and the conjugated, i.e., acetylsulfate, forms of EP had peaks around mid-dark (AZT 18), in antiphase to the NE peak, and had a trough around AZT 12. Since both forms of EP showed the same fluctuation pattern, EP content in free form was regulated mainly by phenylethanolamine N -methyltransferase (PNMT) but not by hydrolysis of the conjugated EP. Since the enzymatic activities of monoamine oxidase (MAO), catechol O -methyltransferase (COMT) and aldehyde reductase (AR) were low, the fluctuation of these amines must be regulated by N -acetyltransferase (NAT), dopamine ß-hydroxylase (DBH) and PNMT.     

MAO, COMT, and GABA-T Activities in Primary Astroglial Cultures

Cultures from cerebral hemispheres of newborn rats contain the enzymes monoamine oxidase (MAO), catechol-O-methyltransferase (COMT), and gamma-aminobutyric acid alpha-ketoglutarate transaminase (GABA-T). The COMT activity was higher in the cultures than in adult rat cerebral hemispheres. The MAO activity was comparable in the cultures and in the rat cerebral hemispheres. The activities of both these enzymes increased with age in the cultures and in the rat brain hemispheres. In the culture the activities were further potentiated by removal of fetal calf serum and addition of 0.1 mM dibutyryl-cyclic AMP (dB-cAMP). GABA-T activity was, however, lower in the cultures than in the adult rat brain hemispheres. The activity increased in brain during postnatal maturation. No changes in the enzyme activity were observed in the cultures, either during growth or after removal of fetal calf serum and addition of dB-cAMP.     

Effect of phenylethanolamine N-methyltransferase and dopamine-beta-hydroxylase inhibition on epinephrine levels in the brain.

The effects of phenylethanolamine N-methyltransferase (PNMT) and dopamine-β-hydroxylase (DβH) inhibition on the epinephrine content in specific regions of the brain were studied. SKF 64139, a potent PNMT inhibitor, is effective in lowering brain epinephrine levels. The time course of PNMT inhibition by SKF 64139 parallels the lowering of epinephrine levels in the brain. Diethyldithiocarbamate (DDC), a potent inhibitor of DβH, is effective in lowering norepinephrine and epinephrine levels and in elevating dopamine levels in the analyzed regions of the brain. The epinephrine levels in the brain appear to be under similar biosynthetic control as in the adrenal glands.     

Pituitary and ovarian responses to luteinizing-hormone-releasing hormone during pregnancy and after parturition in brown hares (Lepus europaeus)

Female hares were given an i.v. injection of 5 micrograms luteinizing-hormone-releasing hormone (LHRH) between Days 7 and 19 (n = 21), 20 and 33 (n = 17) and 34 and 41 (n = 17) of pregnancy, and in the 3 days after parturition (n = 16). Whatever the stage of pregnancy, the LHRH injection induced a release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) and an acute secretion of progesterone; these hormonal responses increased significantly during pregnancy, to reach values similar to those observed in nonpregnant, nonpseudopregnant females during the breeding season in the 3 days after parturition. However, the release of LH remained monophasic in pregnant and post-partum females, in contrast to the unmated females during the reproductive season, in which there was a biphasic profile. The proportion of ovulating females after LHRH treatment was approximately 60% at the beginning and end of pregnancy; and, after parturition, fell to 23% between Days 20 and 33. After Day 33, the pituitary response to LHRH was significantly higher in ovulating than in nonovulating females. At the beginning of pregnancy, 67% of females aborted after LHRH injection; after Day 20, the incidence of abortion decreased significantly and was 0% from Day 34. The amplitude and duration of progesterone secretion by the new corpora lutea resulting from ovulation after LHRH injection were similar to those of corpora lutea induced in nonpregnant females during the breeding season.(ABSTRACT TRUNCATED AT 250 WORDS)     

Asthma pregnancy alters postnatal development of chromaffin cells in the rat adrenal medulla

Background

Adrenal neuroendocrine plays an important role in asthma. The activity of the sympathoadrenal system could be altered by early life events. The effects of maternal asthma during pregnancy on the adrenal medulla of offspring remain unknown.

Methodology/Principal Findings

This study aims to explore the influence of maternal asthma during pregnancy on the development and function of adrenal medulla in offspring from postnatal day 3 (P3) to postnatal day 60 (P60). Asthmatic pregnant rats (AP), nerve growth factor (NGF)-treated pregnant rats (NP) and NGF antibody-treated pregnant rats (ANP) were sensitized and challenged with ovalbumin (OVA); NP and ANP were treated with NGF and NGF antibody respectively. Offspring rats from the maternal group were divided into four groups: offspring from control pregnant rats (OCP), offspring from AP (OAP), offspring from NP (ONP), and offspring from ANP (OANP). The expressions of phenylethanolamine N-methyltransferase (PNMT) protein in adrenal medulla were analyzed. The concentrations of epinephrine (EPI), corticosterone and NGF in serum were measured. Adrenal medulla chromaffin cells (AMCC) were prone to differentiate into sympathetic nerve cells in OAP and ONP. Both EPI and PNMT were decreased in OAP from P3 to P14, and then reached normal level gradually from P30 to P60, which were lower from birth to adulthood in ONP. Corticosterone concentration increased significantly in OAP and ONP.

Conclusion/Significance

Asthma pregnancy may promote AMCC to differentiate into sympathetic neurons in offspring rats and inhibit the synthesis of EPI, resulting in dysfunction of bronchial relaxation.     

Contribution of Sulfate Conjugation, Deamination, and O-Methylation to Metabolism of Dopamine and Norepinephrine in Human Brain

Abstract: The kinetic constants were determined for dopamine (DA) and norepinephrine (NE) metabolism by phenolsulfotransferase (PST), type A and B monoamine oxidase (MAO), and membrane-bound and soluble catechol- O - methyltransferase (COMT) in frontal lobe preparations of human brain. PST and membrane-bound COMT were found to have the lowest K _m, values for both catecholamines. By means of the appropriate rate equations and the calculated kinetic constants for each enzyme, the activity of each enzymatic pathway was determined at varying concentrations of DA and NE. Results indicate that deamination by MAO is the principal pathway for the enzymatic inactivation of DA whereas NE is largely metabolized by MAO type A and membrane-bound COMT under the in vitro assay conditions used. At concentrations less than 100 μ M , soluble COMT'contributes less than 5% to the total catabolism of either catecholamine. PST can contribute up to 15% of the total DA metabolism and 7% of NE metabolism.