Biomedical subjects

M Jakubowski

Publications and source records attributed to M Jakubowski.

At least 19 recordsLinked to original sources

PubMed2006

Forced magnetic reconnection and field penetration of an externally applied rotating helical magnetic field in the TEXTOR tokamak.

The magnetic field penetration process into a magnetized plasma is of basic interest both for plasma physics and astrophysics. In this context special measurements on the field penetration and field amplification are performed by a Hall probe on the dynamic ergodic divertor (DED) on the TEXTOR tokamak and the data are interpreted by a two-fluid plasma model. It is observed that the growth of the forced magnetic reconnection by the rotating DED field is accompanied by a change of the plasma fluid rotation. The differential rotation frequency between the DED field and the plasma plays an important role in the process of the excitation of tearing modes. The momentum input from the rotating DED field to the plasma is interpreted by both a ponderomotive force at the rational surface and a radial electric field modified by an edge ergodization.

Journal Article↗

PubMed2005

Toroidal plasma rotation induced by the dynamic ergodic divertor in the TEXTOR tokamak.

The first results of the Dynamic Ergodic Divertor in TEXTOR, when operating in the m/n=3/1 mode configuration, are presented. The deeply penetrating external magnetic field perturbation of this configuration increases the toroidal plasma rotation. Staying below the excitation threshold for the m/n=2/1 tearing mode, this toroidal rotation is always in the direction of the plasma current, even if the toroidal projection of the rotating magnetic field perturbation is in the opposite direction. The observed toroidal rotation direction is consistent with a radial electric field, generated by an enhanced electron transport in the ergodic layers near the resonances of the perturbation. This is an effect different from theoretical predictions, which assume a direct coupling between rotating perturbation and plasma to be the dominant effect of momentum transfer.

Journal Article↗

PubMed2005

Effects of sensitization of trigeminovascular neurons to triptan therapy during migraine.

Migraine is a neurological disorder which leads to recurring, unilateral, throbbing headache, associated with variable incidence of aura (i.e., visual, sensory and motor function disturbances), nausea and vomiting, photophobia and phonophobia, fatigue, and enhanced irritability. We have recently shown that migraine headache is also associated with high incidence of ipsilateral cutaneous allodynia, particularly in periorbital and temporal skin areas. Patients who experience cutaneous allodynia during migraine feel that their skin hurts in response to otherwise innocuous activities such as combing, shaving, taking a shower, or wearing glasses or earrings. Here, we present evidence to support the view that the development of throbbing in the initial phase of migraine is mediated by sensitization of peripheral trigeminovascular neurons that innervate the meninges, and that the development and maintenance of cutaneous allodynia later in the attack is propelled by sensitization of central trigeminovascular neurons which receive converging sensory input from the meninges as well as from the scalp and facial skin. We also present evidence that the development of cutaneous allodynia during migraine is detrimental to termination of acute migraine attacks using triptans (5HT1B/1D receptor agonist).

Blood Vessels↗

PubMed2004

The effects of environmental cadmium exposure on kidney function: the possible influence of age.

The study aimed to assess the possible influence of long-term environmental exposure to cadmium and age at the time of exposure on renal function. The study was a follow-up of the 1991-1994 project concerning 2000 inhabitants of a cadmium-contaminated area in the vicinity of a zinc smelter. Since the smelter was built in the late 1950s but was not operated until 1968, some of the inhabitants were not exposed to cadmium during childhood. For the follow-up, 308 persons who in 1993 presented with Cd-U levels > or = 0.5 microg/L adjusted for specific gravity (1.020) were selected in 2000. The study population included 136 people who were exposed to cadmium in childhood (former children) and 172 adults (unexposed adults) with no such exposure. These two groups were divided into subgroups according to Cd-U levels: < or =1 (group 1), 1-2 (group 2), and > or =2 microg/g creatinine (group 3). Urinary and blood cadmium and the markers of renal tubular dysfunction (beta2 M-U, RBP-U, NAG, NAG-A, NAG-B) and glomerular dysfunction (Alb-U and beta2 M-S) were measured. Persons with a history of occupational exposure to cadmium were excluded from this project. In group 3 of the unexposed adults, concentrations of RPB-U, NAG, NAG-B, and Alb-U were significantly higher than those in group 1. In former children, this could be observed only for RPB-U and Alb-U. Urine concentrations of these markers were higher in all of the subgroups of former children than in the groups of unexposed adults (except for NAG and its two forms). However, these differences were significant only for RBP-U in group 3. The findings indicate that early renal effects in the general population may occur at Cd-U concentrations above 2 microg/g creatinine and at lower levels for NAG-B. Moreover, cadmium exposure in childhood may have a stronger impact the renal function, particularly tubular reabsorption, than the exposure of a mature organism.

Adolescent↗

PubMed2002

Observation of coherent sheared turbulence flows in the DIII-D Tokamak.

Time-resolved measurements of the turbulent density flow field in a tokamak plasma reveal low-frequency ( approximately 15 KHz), coherent oscillations in the poloidal flow, v(theta). These flow oscillations have a long poloidal wavelength (m<3) and narrow radial extent (k(r)rho(i) approximately 0.2). The estimated flow-shearing rate is of the same order of magnitude as the turbulence decorrelation rate and may thus regulate the turbulence amplitude. These features are consistent with theoretically predicted axisymmetric, self-regulating, sheared flows recognized as geodesic acoustic modes.

Journal Article↗

PubMed2002

Reversibility of microproteinuria in nickel-cadmium battery workers after removal from exposure.

OBJECTIVES: The study was aimed at assessing the reversibility of renal tubule dysfunction in workers exposed to cadmium according to the severity of microproteinuria, concentrations of cadmium in urine (Cd-U), and the time since removal from exposure. METHODS: The study was carried out in a nickel-cadmium battery factory. Exposure to cadmium was formerly very high. In 1983 and in 1986-1988, geometric mean concentrations of cadmium in blood (Cd-B) of workers amounted to 23.3 micro g/l and 55.7 microg/l, respectively. Workers with determinations of Cd-B, Cd-U and retinol binding protein in urine (RBP-U) in the past were eligible for the study. Fifty-eight workers who had met this profile and had been removed from exposure to cadmium before 1998 were investigated in 1998-1999. They were divided into three groups according to their RBP-U concentrations in 1986-1988: <300 ( n=26); 301-1,501 ( n=25) and >1501 microg/g creatinine ( n=7). RESULTS: In 1999, the RPB-U levels were below 300 microg/g creatinine in 85%, 64% and 42% of persons from groups 1, 2 and 3, respectively. Statistical analysis of the results by means of multi-parametric logistic regression analysis revealed that, from the viewpoint of reversibility of tubular proteinuria, its severity in 1986-1988 was most important. Also, the time since the removal from exposure to cadmium and Cd-U levels seemed to play some role, but the influence of these parameters was not statistically significant. Significant correlation between beta(2)-microglobulin in serum (beta(2)M-S) and RBP-U concentrations measured in 1998-1999 with apparent lack of correlation between beta(2)M-S and RBP-U concentrations in 1986-1988 supports the hypothesis that the glomerular impairment induced by cadmium may be secondary to the tubular lesion rather than independent from tubular effect. CONCLUSIONS: The results show that the tubular proteinuria, and maybe also the decline in glomerular filtration rate, may be reversible, even in the case of relatively high past exposure. The results confirm the necessity for monitoring urinary levels of low-molecular-weight proteins during periodic examination of workers exposed to cadmium.

Adult↗

PubMed2002

Long-term effects of the mammary carcinogen 7,12-dimethylbenz(a) anthracene on hypothalamic gonadotropin-releasing hormone and its pituitary receptor gene expression, during the promotion stage, in female Sprague-Dawley rats.

A single intragastric administration of 7,12-dimethylbenz(a)anthracene (DMBA) has been shown to induce mammary tumors in young cycling female Sprague-Dawley rats. The appearance of these tumors is preceded by a series of neuroendocrine disturbances, including attenuation of the preovulatory luteinizing hormone (LH) surge and amplification of the preovulatory 17beta-estradiol surge, and gonadotropin-releasing hormone (GnRH) released in vitro. In this study, we examined the hypothesis that DMBA administration decreases levels of GnRH mRNA in the preoptic area-anterior hypothalamus (POA-AH) and GnRH receptor (GnRH Rc) mRNA and protein in the anterior pituitary gland. Sprague-Dawley rats, 55-60 days of age with regular estrous cycles, received a single dose of 15 mg DMBA in 1 ml sesame oil delivered by intragastric intubation. A first series of experiments was performed for the measurement of hypothalamic GnRH mRNA and pituitary GnRH Rc mRNA levels. A second series of experiments was performed for the measurement of pituitary GnRH receptor. In both experiments, animals were sacrificed by decapitation at 11.00, 16.00, 18.00 and 20.00 h on each day of the 7th or 8th estrous cycle (28-32 days) after treatment. GnRH and GnRH receptor mRNAs were quantified using solution hybridization-RNase protection assay. The GnRH Rc was quantified using the 125I-D-Ala6-N-Met-Leu6-des-Gly10-ethylamide GnRH. DMBA-treatment produced no significant effect on the overall mean values of GnRH mRNA. GnRH mRNA levels in control rats rose significantly between 16.00 and 20.00 h on proestrus and between 18.00 and 20.00 h on diestrus I. DMBA-treated rats had a surge in GnRH mRNA levels at 18.00 h on proestrus, and showed additional surges at 18.00h on diestrus II and estrus. GnRH receptor mRNA content in the anterior pituitary gland surged at 16.00h on certain days of the cycle in both groups of rats. In control rats, only the surge on diestrus II proved significant, whereas DMBA-treated rats exhibited significant surges on diestrus I, diestrus II and proestrus. GnRH receptor mRNA values were significantly lower on both days of diestrus in DMBA-treated rats compared with controls. GnRH Rc peptide content, like GnRH receptor in RNA surged at 16.00h in both groups with the exception of a marked fall on proestrus day for DMBA treated rats. A reduction in the amplitude of the surge was also seen on the day of estrous and to a lesser extend on the day of diestrus DII in DMBA treated animal. Overall, there was a disruption of the GnRH Rc pattern which culminate on the day of proestrus in DMBA-treated animals. Interestingly, the daily rise between 11.00 and 16.00h which is the more pronounced on the day of proestrus in control animals, was completely blunted in DMBA-treated rats. Overall, the results are consistent with the hypothesis that the carcinogen attenuates, directly or indirectly, preovulatory biosynthesis of the GnRH receptor and LH release. Obviously, the changes in GnRH might occur simultaneously, independently from mammary tumorigenesis, but may play a role, in association with others DMBA-induced neuroendocrine disorders, in the promotion stage of mammary tumors in the Sprague-Dawley female rat.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed2002

Two generations of the tongue and gustatory organs in the development of Hynobius dunni Tago.

In the development of Hynobius dunni there are two consecutive generations of the tongue and two generations of gustatory organs (taste buds and taste disks). The anlage of the developing secondary tongue appears just in front of the free ending of the primary tongue beginning at the larval developmental stage 62. From stage 67, a gradual reduction in the anterior part of the gill skeleton that supports the primary tongue occurs as the developing secondary tongue replaces the primary one. The lining of the entire oropharyngeal cavity of larvae contains only gustatory organs of the taste bud (TB) type. In younger larvae, the sensory area of a TB has a diameter of between 10 and 13 microm, while in older larvae, TBs reach 16-18 microm in diameter. After metamorphosis, some gustatory organs in the secondary tongue with a sensory area of 26-36 microm in diameter appear. In older animals they may reach as much as 56-71 microm. In other regions of the oropharyngeal epithelium than the tongue, these organs have an ellipsoid shape with a major axis of about 50 microm. On the basis of the cytomorphological criteria established previously, these organs were designated as taste disks. Thus, the presence of two generations of gustatory organs is characteristic of some urodeles, as well as frogs.

Animals↗

PubMed2002

Development of mucous cells in taste discs of anurans.

Differentiation of the lingual taste discs (TDs) was studied in tadpoles of Rana esculenta, Hyla arborea and Pelobatesfuscus by means of LM, TEM, and SEM. The process of differentiation of mucous cells (MCs) within a TD anlage was investigated subsequently from 39th to 46th Gosner's developmental stage. In R. esculenta and P. fuscus, the MCs are distinguishable in TD anlages not earlier than at the 42nd tadpole Gosner's stage. At that stage TDs anlages are covered by a single layer of ordinary epithelial cells. Starting from the stage 44, tips of TDs progressively open outside and free surfaces of MCs can be distinguished as an area with numerous microfolds. At developmental stages 45 and 46, numerous electron-dense secretory granules can be seen in the supranuclear cytoplasm of MCs. The presence of mucopolysaccharides in H. arborea and P. fuscus was observed from the 44th-45th tadpole developmental stage.

Animals↗

PubMed2001

A neurohistochemical blueprint for pain-induced loss of appetite.

A common complaint among pain patients is that they lose their appetite. These accounts are anecdotal, however, and the neural mechanism underlying pain-induced loss of appetite remains unknown. In this study, we documented the occurrence of appetite loss in patients under migraine attack and investigated the neuronal substrate of pain-induced anorexia in our animal model of intracranial pain. We found that loss of appetite during the migraine attack in humans coincided strongly with the onset and duration of the head pain in 32/39 cases, and that brief noxious stimulation of the dura in conscious rats produced a transient suppression of food intake. Mapping of neuronal activation in the rat showed that noxious dural stimulation induced a 3- to 4-fold increase in the number of Fos-positive neurons in medullary dorsal horn areas that process nociceptive signals (laminae I, V) and in parabrachial and hypothalamic neurons positioned to suppress feeding behavior. In the parabrachial area, activated neurons were localized in the superior-lateral subnucleus, and 40% of them expressed the mRNA encoding the anorectic neuropeptide cholecystokinin. In the hypothalamus, activated Fos-positive neurons were found in the dorsomedial area of the ventromedial nucleus, and 76% of them expressed the mRNA for cholecystokinin type-B receptor. Based on these findings, we suggest that at least one of several groups of hypothalamic neurons that normally inhibit appetite in response to metabolic cues is positioned to mediate the suppression of food intake by pain signals.

Animals↗

PubMed2001

Morphological differentiation of taste organs in the ontogeny of Salamandra salamandra.

Morphological studies presented here provide additional cytological evidence that in the postnatal development of Salamandra salamandra there are two successive generations of taste organs: premetamorphic taste buds (TBs) in larval forms and taste disks (TDs) in postmetamorphic animals. The TBs have been found in the epithelium of the whole oropharyngeal cavity of larval forms, while in adults TDs appear only at the end of metamorphosis. The TDs can be papillary (or fungiform) on the soft (secondary) tongue and non-papillary outside the tongue. Two main cyto-morphological criteria distinguishing TDs from TBs have been established: (1) high differentiation of "nonsensory" components of a taste organ into several kinds of cells (often named "associate cells")--at least mucous cells and, separating them, wing cells; (2) a considerably larger area of the sensory epithelium than that in TBs, as the consequence of the large size of the mucous cells. In contrast to TDs each TB consists of longitudinally elongated supporting cells and taste cells, as well as of horizontally oriented basal cells, adjacent to the basement membrane. The sensory area in TBs measures 10-12 microm in diameter, while that in TDs has diameter of 45-90 microm. The anlage of the secondary tongue appears as a small folding of the floor epithelium just in front to the tip of the primary tongue in larvae 3 cm long, and is definitely formed in an animal with body length of about 6 cm.

Animals↗

PubMed2001

Neurological and neurophysiological examinations of workers occupationally exposed to manganese.

The nervous system is the major target of the toxic effect of manganese (Mn) and its compounds. Nowadays, neurological diagnostics is directed towards early detection of symptoms and abortive forms, and the cases of serious damage of the nervous system are no longer reported. The aim of the present study was to assess the effects of manganese on the functions of the nervous system in workers exposed to this metal in the ship and electrical industries. The study covered a selected group of 75 male workers (mean age 39.17 yr +/- 9.79; range 20-56 yr), including 62 welders and fitters, as well as 13 workers involved in the battery production. Their employment duration ranged between 1 and 41 yr (mean 17.5 yr +/- 10.81). During the welding process the air Mn concentrations varied from 0.004 to 2.67 mg/m3 (arithmetic mean, 0.399 mg/m3; geometric mean, 0.154 mg/m3; standard deviation, 0.586). Of the 62 workers, 30 worked in the area with exceeding MAC value of 0.3 mg/m3. At the battery production workposts, Mn concentrations fell within 0.086-1.164 mg/m3 (arithmetic mean, 0.338 mg/m3, geometric mean, 0.261 mg/m3; standard deviation, 0.292). The values of current Mn exposure in the study group fell within the range below 0.01 and 2.67 mg/m3 (arithmetic mean, 0.4 mg/m; geometric mean, 0.15 mg/m3). Of the 13 subjects, 6 worked at the Mn air concentration exceeding MAC values. In the exposed group, the values of cumulated exposure index ranged from 0.008 to 35.52 (arithmetic mean, 8.045; geometric mean, 4.615; standard deviation, 6.562). The control group consisted of 62 men non-occupationally exposed to Mn, matched by sex, age and work shift distribution. Clinically, the increased emotional irritability, dysmnesia, concentration difficulties, sleepiness and limb paresthesia predominated among the disorders of the nervous system functions in workers chronically exposed to manganese. Neither in the central nor in the peripheral nervous system, the objective examinations revealed organic lesions that could provide grounds for diagnosing toxic encephalopathy or polyneuropathy. Generalized and paroxysmal changes were the most common recordings in the abnormal electroencephalography. Visual evoked potentials examinations showed abnormalities in the response evoked, which could be a signal of the optic neuron disorders and their significant relationship with cumulated exposure. The results of the study demonstrate that Mn exposure within the range of <0.01-2.67 mg/m3 (arithmetic mean, 0.4 mg/m3; geometric mean, 0.15 mg/m3) induces subclinical effects on the nervous system.

Adult↗

PubMed1998

The disposition and metabolism of 1,3,5-[U-14C]trioxane in male Wistar albino rats.

The present study was designed to investigate 1,3,5-[U-14C]trioxane (TOX) distribution, excretion and metabolism. The experiments were performed on male Wistar albino rats after a single administration of TOX at doses of 40 mg/kg and 400 mg/kg. The exhaled air proved to be the main route of 14C elimination, mainly as 14CO2. During the first 12 h following the administration of 40 mg/kg of TOX the exhalation of 14CO2 was monophasic, with a half-life of 3.5 h. After the administration of 400 mg/kg, TOX was eliminated mainly as 14CO2 with the exhaled air (77%) and unchanged TOX (8%). About 3% of 14C was excreted in the urine as unchanged 1,3,5-trioxane. With regards to TOX elimination from blood plasma for the lower dose, a biphasic process was observed, with half-lives of 4.5 and 72 h. The amount of 14C bound by the erythrocytes was minute compared with the amount in blood plasma. When the higher dose of TOX was administered the efficiency of 14C binding to the erythrocytes was found to be 10 times higher than the respective value for blood plasma. Among the examined tissues the highest concentration of TOX-derived radioactivity was detected in the liver while the lowest was in fat tissue and brain. A subsequent decay of radioactivity occurred in the tissues. The results of the present study indicate that TOX belongs to the group of compounds, which are rapidly eliminated from the organism; hence TOX should not be expected to accumulate within the tissues. The data obtained confirm the assumed pattern of metabolic transformation, according to which 1,3,5-trioxane undergoes enzymatic transformation to formaldehyde, with carbon dioxide and water being the final products.

Animals↗

PubMed1998

Blood lead levels in industrial workers in Poland.

Occupational exposure to lead occurs in about 1,300 enterprises in Poland. According to the 1994 data, based on the reports of the State Sanitary Inspectorate, 1,970 persons were employed at that time under conditions of exposure exceeding the Polish MAC level of 0.050 mg/m3. The measurements of workers' blood lead concentrations (Pb-B) were carried out only in 90 factories. In 1996, the Minister of Health and Social Welfare issued a directive stating that the Pb-B determinations in employees occupationally exposed to lead are compulsory. The aim of the present study was to assess lead exposure of workers employed in different branches of the Polish economy, based on Pb-B determinations. The measurements were performed on 2,324 male and 165 female workers of 13 different types of industry, including manufacture of crystal glass, battery industry, copper and zinc smelters, welding in a repair shipyard and some other workposts under conditions of lead exposure. The results of the determinations indicate that exposure to lead continues to be a serious problem in Polish industry. Pb-B concentrations exceeded the newly introduced Polish biological exposure index (BEI) value of 500 micrograms/l for men workers in about 30% of workers examined in 1996. In about 65% of females under 45 years of age the Pb-B concentrations were higher than 300 micrograms/l recommended as BEI for this age group. Considering the WHO-recommended health-based maximum individual biological action level of 400 micrograms/l, the percentage of the employees for whom higher values were found amounted to about 45% for men workers. The results point to the necessity of enforcing the implementation of Pb-B determinations according to the ministerial ordinance as well as of removing from exposure the workers with Pb-B levels exceeding the present BEI values. The improvement of working conditions and the implementation of health education for workers are also the actions to be promptly undertaken. In order to achieve these goals a close cooperation is required between the State Sanitary Inspectorate, the institutes of occupational health as well as the employers and trade unions.

Adult↗

PubMed1998

Biological monitoring of occupational exposure to arsenic by determining urinary content of inorganic arsenic and its methylated metabolites.

A study was undertaken to assess the relationship between inhalation exposure to arsenic in copper smeltery workers and urinary excretion of total inorganic arsenic metabolites (Asitm), including inorganic arsenic (Asi), monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA). The methods applied made it possible, in principle, to determine all forms of airborne arsenic and to eliminate the influence of seafood-derived organoarsenicals on the level of urinary Asitm. Air samples were collected on the second day of work after the weekend break. Urine samples were collected just after shift-end on the same workday. The time-weighted average (TWA) concentrations of arsenic in the workers' breathing zone varied between 1 and 746 microg/m3 and Asitm concentrations in urine between 2 and 850 microg/l (s.g. 1.024). The urine samples with a specific gravity of lower than 1.010 and higher than 1.030 were not considered; neither were those subjects with an Asitm excretion efficiency of higher than 100% of the dose absorbed during the day of measurement. In total, 53 air samples and corresponding urine samples were obtained. The correlation coefficient between the airborne arsenic concentration in microg/m3 (X) and the concentration of urinary Asitm in microg/l, s.g. 1.024 (Y), was 0.723. The relation between the two variables can be presented using the following formula: Y = 6.29 x X0.616. According to the findings of this study, as well as the results of three other studies based on similar principles, the daily exposure to arsenic concentrations of 10 microg/m3 and 50 microg/m3 led to concentrations of Asitm in urine of about 30 microg/l and 70 microg/l (s.g. 1.024), respectively.

Arsenic↗

PubMed1997

Elimination of 1-hydroxypyrene after human volunteer exposure to polycyclic aromatic hydrocarbons.

The aim of this study was to estimate the kinetics of 1-hydroxypyrene (1-HP) elimination after inhalation exposure to polycyclic aromatic hydrocarbons (PAHs). Samples of inhaled and exhaled air were collected on glass fiber filters backed with tubes filled with Amberlit XAD-2 resin. The filters were extracted by cyclohexane and Amberlit--by acetonitrile. Extracts for the determination of pyrene and benzo[a]pyrene (B[a]P) concentrations were analyzed by high-performance liquid chromatography (HPLC). 1-Hydroxypyrene in urine was determined after its preconcentration on a C-18 column (solid phase extraction method) using the same analytical technique. Five male volunteers were exposed for 6 h (two times, with a 1-month interval) to a PAH mixture at an aluminium plant. The volunteers were breathing at rest through facial mask equipped with a 1000-ml compensation container which allows collection of the exhaled air. Inhaled air samples were collected in the breathing zone of each volunteer. Urine samples were collected until the 71st hour after the onset of exposure. The average respiratory retention of pyrene was found to be 61%. The 1-HP elimination process could be described by one-compartment model with the half-live of 9.8 hour (95% CI 7.9-11.7 h). The simulation of 1-HP elimination in urine during a working week (4 days) indicates that the balance between absorption and elimination is achieved at the end of the second day.

Administration, Inhalation↗

PubMed1997

The present state of occupational medicine in Poland.

Occupational medicine in Poland has a long tradition, dating back to the establishment of the first health-care institutions for industrial workers at an early stage of Poland's industrialization. Legal foundations of the industrial health-care system, based on the Soviet model, were enacted in 1953. During its most dynamic period of development (1970s and 1980s) the industrial health-care system provided medical services to about 6 million workers. The process of the political and economic transition in Poland began in 1989, and since 1991 there have been numerous transformations in the structure and function of industrial health services. The present article describes the main stages of the transformation process, occupational health training, research, advisory bodies, and the system for setting of hygienic standards.

Education, Medical↗

PubMed1997

Endopeptidase EC 3.4.24.15 presence in the rat median eminence and hypophysial portal blood and its modulation of the luteinizing hormone surge.

The endopeptidase EC 3.4.24.15 (EP24.15) is a zinc metalloendopeptidase that is widely distributed in a variety of tissues, including the testes, pituitary and the central nervous system. Among its numerous roles in metabolizing and processing biologically-active peptides, the enzyme degrades gonadotropin-releasing hormone (GnRH) by cleaving the central Tyr5-Gly6 bond. The aim of the present studies was to determine whether EP24.15 can modulate the concentrations of GnRH within the hypothalamo-hypophysial portal blood and thereby play a physiological role in reproduction. Our data suggest the presence of immunoreactive EP24.15 in the perivascular space of the median eminence and that this enzyme is secreted into portal blood. We have also shown a physiological role for this enzyme in that an inhibition of its activity with a specific inhibitor augmented the steroid-induced LH increase in ovariectomized rats. The present results suggest that secretory and post-secretory mechanisms are important in shaping the GnRH signal from the central nervous system; GnRH metabolism by EP24.15 may be one such mechanism.

Animals↗