Biomedical subjects

S Vigh

Publications and source records attributed to S Vigh.

At least 37 records · Page 2Linked to original sources

PubMed1987

Potent GnRH agonists containing L-amino acid derivatives in the six position.

New agonists related to gonadotropin-releasing hormone (GnRH) have been synthesized that are comparable in potency to the GnRH and its superagonists for release of LH and estrus suppression without substitutions with D- or unnatural amino acids in position 6. We now report a series of L-beta-aspartyl-6 GnRH analogs containing only naturally occurring L-amino acids in the whole sequence, exhibiting considerable in vivo biological activity. Dose and time dependent LH release capability of the different analogs in adult male mice, estrus suppression comparisons and blockade of ovulation in female rats are given. The incorporation of L-Asp-OMe and L-Asp-OBzl in position 6 of GnRH resulted in the most potent GnRH agonists (to 12-20xGnRH potency) in this series inducing a biphasic biological response similar to the D-amino acid-6 substituted superactive GnRH analogs. A correlation between the LH releasing potencies of the analogs and their HPLC retention times was also investigated. Peptide synthesis were achieved using either solid phase or solution phase methodology.

Animals↗

PubMed1986

Comparison of in vitro and in vivo effects of different species specific GnRH and their analogs.

Mammalian, salmon and chicken gonadotropin-releasing hormones (mGnRH, sGnRH, cGnRH) and their analogs were synthesized and tested for their ability to stimulate in vitro LH and FSH release from cultured and superfused rat pituitary cells and also their in vivo effect were investigated on the artificial propagation of fishes. The LH and FSH releasing activity of sGnRH, cGnRH and their analogs were lower than the appropriate mammalian ones from cultured rat pituitary cells, but two of the cGnRH analogs showed increased LH and FSH secretory activity from superfused rat pituitary cells compared to the mGnRH. At the same time these two analogs are very potent to stimulate reproductive function of fishes and using these peptides we were able to fulfill the artificial propagation of fishes which could not be artificially propagated before.

Amino Acids↗

PubMed1986

Ontogenetic development of corticotropin-releasing factor (CRF)-containing neural elements in the brain of the chicken during incubation and after hatching.

In chicken embryos of different ages and in young chickens after hatching, neural elements reacting with antibodies generated against synthetic ovine corticotropin-releasing factor (CRF) were studied by means of the peroxidase-anti-peroxidase (PAP) technique at the light-microscopic level. CRF-immunoreactivity was first observed in perikarya located in the periventricular part of the hypothalamus on the 14th day of the incubation period. CRF-containing neural elements were detected on the same day of incubation in the external zone of the median eminence, but not in all investigated animals. In extrahypothalamic sites, immunoreactive perikarya were demonstrable in the central gray of the mesencephalon on the 15th day of incubation. Furthermore, immunoreactive cells appeared in other brain regions such as nucleus accumbens and dorsomedial nucleus of the thalamus after hatching. The present observations provide information regarding the functional development of the hypothalamo-hypophyseal-adrenal axis in the chick embryo.

Aging↗

PubMed1985

Corticotropin-releasing factor (CRF)-immunoreactive neurons in the mammillary body of the rat.

The presence and distribution of CRF-immunoreactive cells and nerve fibers were studied in the mammillary body of the rat, 12 days after placing various types of lesions within the hypothalamus. Anterior and anteriolateral cuts, placed in the midhypothalamus immediately behind the paraventricular nuclei resulted in an almost complete disappearance of CRF-immunoreactive fibers from the median eminence and simultaneous appearance of CRF-containing neurons in the mammillary body. Posterior or postero-lateral hypothalamic cuts carried out in front of the mammillary body caused the accumulation of CRF-immunoreactive material in neurons and neural processes located behind the cut-line. This type of intervention had no effect on the quantity of CRF fibers in the median eminence. A cut running through the central part of the mammillary body in the frontal plane resulted in appearance of CRF neurons only in the posterior half of the mammillary region. Placing a cut behind and over the mammillary body, CRF-immunoreactive neurons became detectable below the superior cut-line. No immunoreactive neurons were observed in the mammillary body when the frontal cut reached the base of the brain at the posterior border of the nucleus, leaving intact its anterior and superior connections. In all these cases when the mammillo-thalamic tract was transected, CRF neurons became detectable in the mammillary body.

Animals↗

PubMed1985

The origin and ultrastructural characteristics of corticotropin-releasing factor (CRF)-immunoreactive nerve fibers in the posterior pituitary of the rat.

A fine network of corticotropin-releasing factor (CRF)-immunopositive fibers was found in the posterior lobe of the pituitary of the rat. The intermediate and distal lobes were free of CRF-immunoreactivity. Varicose, terminal-like axons were frequently observed around capillary vessels. Surgical isolation of the paraventricular nuclei resulted in a complete disappearance of CRF-immunoreactive fibers from the posterior lobe. CRF-immunopositive fibers show the general characteristics of peptidergic axons. These ultrastructural observations support the idea that CRF is secreted into capillary vessels.

Animals↗

PubMed1985

Evidence for local corticotropin releasing factor (CRF)-immunoreactive neuronal circuits in the paraventricular nucleus of the rat hypothalamus. An electron microscopic immunohistochemical analysis.

The interrelationships of corticotropin-releasing factor (CRF) immunoreactive neuronal cell bodies and processes have been examined in the paraventricular nucleus (PVN) of adrenalectomized-dexamethasone treated rats. Antisera generated against ovine CRF (oCRF) were used in the peroxidase-anti-peroxidase-complex (PAP)-immunocytochemical method at both the light and electron microscopic levels. In this experimental model, a great number of CRF-immunoreactive neurons were detected in the parvocellular subdivisions of the PVN and a few scattered labelled parvocellular neurons were also observed within the magnocellular subunits. Characteristic features of immunolabeled perikarya included hypertrophied rough endoplasmic reticulum with dilated endoplasmic cisternae, well developed Golgi complexes and increased numbers of neurosecretory granules. These features are interpreted to indicate accelerated hormone synthesis as a result of adrenalectomy. Afferent fibers communicated with dendrites and somata of CRF-immunoreactive neurons via both symmetrical and asymmetrical synapses. Some neurons exhibited somatic appendages and these structures were also observed to receive synaptic terminals. Within both the PVN and its adjacent neuropil, CRF-immunoreactive axons demonstrated varicosites which contained accumulations of densecore vesicles. CRF-containing axons were observed to branch into axon collaterals. These axons or axon collaterals established axo-somatic synapses on CRF-producing neurons in the parvocellular regions of the PVN, while in the magnocellular area of the nucleus they were found in juxtaposition with unlabeled magnocellular neuronal cell bodies or in synaptic contact with their dendrites. The presence of CRF-immunoreactive material in presynaptic structures suggests that the neurohormone may participate in mechanisms of synaptic transfer. These ultrastructural data indicate that the function of the paraventricular CRF-synthesizing neurons is adrenal steroid hormone dependent. They also provide morphological evidence for the existence of a neuronal ultrashort feed-back mechanism within the PVN for the regulation of CRF production and possibly that of other peptide hormones contained within this complex.

Adrenalectomy↗

PubMed1985

Radioimmunoassay for 6-D-tryptophan analog of luteinizing hormone-releasing hormone: measurement of serum levels after administration of long-acting microcapsule formulations.

A sensitive and specific radioimmunoassay for [6-D-tryptophan]luteinizing hormone-releasing hormone [( D-Trp6]LH-RH) was developed and used for following the rate of liberation of [D-Trp6]LH-RH from a long-acting delivery system based on a microcapsule formulation. Rabbit antibodies were generated against [D-Trp6]LH-RH conjugated to bovine serum albumin with glutaraldehyde. Crossreactivity with LH-RH was less than 1%; there was no significant crossreactivity with other peptides. The minimal detectable dose of [D-Trp6]LH-RH was 2 pg per tube. Intra- and interassay coefficients of variation were 8% and 10%, respectively. The radioimmunoassay was suitable for direct determination of [D-Trp6]LH-RH in serum, permitting the study of blood levels of the analog after single injections into normal men and after once-a-month administration of microcapsules to rats. In men, 90 min after subcutaneous injection of 250 micrograms of the peptide, serum [D-Trp6]LH-RH rose to 6-12 ng/ml. Luteinizing hormone was increased 90 min and 24 hr after the administration of the analog. Several batches of microcapsules were tested in rats and the rate of release of [D-Trp6]LH-RH was followed. The improved batch of microcapsules of [D-Trp6]LH-RH increased serum concentrations of the analog for 30 days or longer after intramuscular injection. This was accompanied by suppression of testosterone levels for more than 30 days. This radioimmunoassay should be of value for monitoring [D-Trp6]LH-RH during long-term therapy.

Animals↗

PubMed1985

Re-evaluation of "frontal deafferentation" studies on the regulation of ACTH secretion in the light of CRF immunohistology.

Frontal afferents to the medial basal hypothalamus of the rat were interrupted by a Halász knife, and 4 weeks later the brains were processed for immunostaining of CRF-fibers. It was found that such intervention saves most of the CRF immunoreactive fibers of the paraventriculo-infundibular tract. Some of the conflicting results of earlier deafferentation studies are discussed on the basis of CRF immunohistology.

Adrenocorticotropic Hormone↗

PubMed1984

Immunocytochemical localization of corticotropin releasing factor (CRF)-like immunoreactivity in the thalamus of the rat.

The distribution of corticotropin releasing factor (CRF)-immunoreactive structures in the rat thalamus was studied after treatment with high doses of colchicine (100 micrograms/100 g b.wt.) with peroxidase-antiperoxidase (PAP) immunocytochemistry in vibratome sections. CRF-immunopositive perikarya were found in the 'posteromedial complex' of the thalamus, including the ventromedial, paracentral, mediodorsal, rhomboid, parafascicular nuclei, centrum medianum and ventromedial portion of the posterolateral nucleus. In addition, CRF-containing perikarya were observed in the pretectal and subthalamic nuclei. CRF-immunoreactive processes were seen in most of the medial nuclei of the thalamus. The presence of CRF-immunopositive structures in the thalamus suggests that CRF not only functions as a hypophysiotropic hormone regulating the release of ACTH and beta-endorphin from the pituitary, but also as a neurotransmitter or neuromodulator, playing an important role in nociception and analgesia.

Afferent Pathways↗

PubMed1984

Localization of corticotropin-releasing factor-containing neurons in the brain of the domestic fowl. An immunohistochemical study.

The corticotropin-releasing factor (CRF)-containing neurons were investigated in the brain of the domestic fowl by means of the peroxidase-antiperoxidase technique at the light-microscopic level. The detection of CRF-immunoreactivity was facilitated by silver intensification. CRF-containing perikarya were found in the paraventricular, preoptic and mammillary nuclei of the hypothalamus and in some extrahypothalamic areas (nuclei dorsomedialis and dorsolateralis thalami, nucleus accumbens septi, lobus parolfactorius, periaqueductal gray of the mesencephalon, nucleus oculomotorius ventralis). Immunoreactive nerve fibers and terminals were demonstrated in the external zone of the median eminence and the organum vasculosum of the lamina terminalis. These results indicate that an immunologically demonstrable CRF-neurosecretory system also exists in the avian central nervous system.

Animals↗

PubMed1984

Corticotropin-releasing factor (CRF)-like immunoreactivity in the gastro-entero-pancreatic endocrine system.

CRF has been detected in the endocrine pancreas by immunocytochemistry with an antiserum that recognizes mainly the C-terminal portion of CRF-41. CRF-containing cells have been shown to be present in the pancreas of representative species of fishes, amphibians, reptiles, birds, and mammals including man. Light and electron microscopic observations indicate that the CRF-containing cells in the endocrine pancreas are similar to glucagon (A) cells both in their morphology and distribution. Individual CRF-containing cells are also found scattered in the exocrine pancreas in all species studied. In addition, CRF-containing cells have been identified in the human, monkey, cat, and rat stomach and small intestine. Recent reports also indicate that CRF-like immunoreactivity is present in the circulating blood, the adrenal medulla, and the placenta. Finally, several peripheral (pancreas, stomach, colon, lung and thyroid) tumors which produced corticotropin-releasing substances have been described by others. Although the peripheral actions of CRF are not yet known, these observations indicate that it is widely distributed in peripheral tissues and it may also represent a new tumor marker.

Animals↗

PubMed1984

Interaction between hypothalamic peptides in a superfused pituitary cell system.

Recently two hypothalamic releasing factors have been isolated, sequenced and synthesized: corticotropin-releasing factor (CRF) from sheep and rat hypothalami; and growth hormone-releasing factor (GH-RF) from tumors in human pancreas (hpGH-RF) and from rat hypothalami (rhGH-RF). Their biological potencies were tested by various laboratories in vivo and in vitro using rat pituitary cell cultures and the pituitary quarters method. In the present study, we investigated the dynamics of the release of pituitary hormones and the interaction between CRF and hGH-RF and several brain peptides in a pituitary cell-superfusion system. A dose-related ACTH release was found when the cells were superfused with different doses of synthetic CRF. Synthetic hGH-RF44, hGH-RF40, hGH-RF1-29 and purified porcine hypothalamic GH-RF caused similar dose-related releases of GH. In this system, we demonstrated interactions between CRF and vasopressin, CRF and SP, hGH-RF and vasopressin and hGH-RF and PHI-27. We conclude that the control of pituitary hormone secretion is a complex process; several factors may interact with each releasing or inhibiting factor to modulate their effects.

Adrenocorticotropic Hormone↗

PubMed1984

Corticotropin releasing factor (CRF): origin and course of afferent pathways to the median eminence (ME) of the rat hypothalamus.

8-10 days after making various lesions in the rat hypothalamus, the presence of corticotropin releasing factor (CRF) immunoreactive neural structures was studied in paraffin and vibratome sections with CRF immunocytochemistry. Bilateral anterolateral deafferentation of the medial basal hypothalamus (MBH) caused complete disappearance of CRF immunoreactivity from the median eminence (ME) in brains where the posterior edge of the cut reached the level of the pituitary stalk. A shorter cut resulted in positive immunostaining caudal to the caudal edge of the cut. Unilateral deafferentation of the MBH caused significant decrease in CRF immunostaining in the ipsilateral ME. Unilateral posterolateral deafferentation of the MBH caused no changes in CRF immunostaining in the rostral ME, while fewer CRF-containing processes were observed in the more caudal regions. A horizontal cut ventral to the paraventricular nuclei (PVN) caused a slight decrease in the number of CRF-immunoreactive profiles in the ME. A wider and complete unilateral horizontal cut resulted in a significant decrease in CRF immunoreactivity on the operated side. Following various surgical interventions, hormone accumulation in cell bodies was detected in the paraventricular, periventricular preoptic, dorsomedial, periventricular, lateral and posterior hypothalamic, and premammillary nuclei. Fibers arising from most of these nuclei formed a fan-like projection to the ME. The majority of the CRF-fibers ran through the lateral tract of the fan, and reached the ME by the lateral-basal retrochiasmatic area (LBRCA). Scattered fibers were detected in the lateral-basal hypothalamus as far caudally as the level of the pituitary stalk. Unilateral anterolateral and horizontal cuts did not result in complete disappearance of CRF immunoreactivity from the ipsilateral ME, indicating the existence of CRF-fibers of contralateral origin in the ME.

Animals↗

PubMed1984

Immunocytochemical localization of growth hormone-releasing factor in the rat hypothalamus.

The distribution of GRF-immunoreactive structures in the rat hypothalamus was studied after colchicine treatment with peroxidase-antiperoxidase immunocytochemistry in vibratome sections. The majority of the GRF-immunoreactive cell bodies were found in the arcuate nucleus and the medial perifornical region of the lateral hypothalamus. Scattered cells were seen in the lateral basal hypothalamus, the medial and lateral portions of the ventromedial nucleus, and the dorsomedial and paraventricular nuclei. Fibers from the perifornical cell bodies formed a fan-like projection to the median eminence, where a dense accumulation of GRF-containing processes and terminals was found. GRF terminals were located in the central regions of the median eminence. The localization of GRF-immunoreactive structures in the hypothalamus and median eminence reinforces the view that GRF plays a physiological role in the regulation of pituitary function.

Animals↗

PubMed1983

Immunocytochemical localization of corticotropin releasing factor (CRF) in the rat spinal cord.

The presence of corticotropin releasing factor (CRF)-immunoreactive nerve fibers and cell bodies in the spinal cord is demonstrated. Immunopositive fibers were found in the lateral column of the white matter, in laminae I, V-VII, X, and in the intermediolateral column of the spinal cord. Complete transection of the spinal cord showed that the majority of the fibers in the lateral funiculus formed an ascending pathway; however, a few descending fibers were also detected. Hypophysectomy resulted in enhanced immunoreactivity of the fibers and staining of CRF-immunoreactive cell bodies in laminae V-VII, X, and in the intermediolateral sympathetic column. The results suggest that CRF is not merely an ACTH releasing factor, but also a regulatory peptide which may be involved in several stress-related neural responses.

Animals↗

PubMed1983

Ultrastructural characteristics of immunolabelled, corticotropin releasing factor (CRF)-synthesizing neurons in the rat brain.

The corticotropin releasing factor (CRF)-synthesizing perikarya and neural processes were detected at ultrastructural level in the hypothalamic paraventricular nucleus and in the median eminence of control and colchicine-pretreated rats. The unlabelled antibody peroxidase-antiperoxidase complex (PAP) immunohistochemical method was used in a pre-embedding manner, on thick, non-frozen sections. In CRF-perikarya, neurosecretory granules (80-120 nm in diameter), free ribosomes, and the rough endoplasmic reticulum were labelled. Unlabelled axon terminals formed asymmetric synapses on CRF-containing perikarya and dendrites. Immunolabelled axons terminated in the palisadic zone of the median eminence.

Animals↗

PubMed1983

The paraventriculo-infundibular corticotropin releasing factor (CRF) pathway as revealed by immunocytochemistry in long-term hypophysectomized or adrenalectomized rats.

The immunocytochemical localization of corticotropin releasing factor (CRF)-containing pathways projecting from the paraventricular nucleus (PVN) to the external layer of the median eminence (ME) in long-term hypophysectomized or adrenalectomized rats is described. Immunocytochemistry was followed by silver intensification of the diaminobenzidine end-product. In comparison with untreated control rats, both hypophysectomy and adrenalectomy resulted in a dramatic increase in immunostaining of the CRF-containing perikarya and fibers, particularly those originating from the PVN and terminating in the ME. The staining was more intense in adrenalectomized than in hypophysectomized rats. The CRF-positive fibers emerging from the PVN form a medial, an intermediate and a lateral fiber pathway. The lateral and intermediate CRF tracts leave the dorsolateral part of the PVN and course laterally and medially of the fornix, respectively, then ventrally toward the optic tract. Just dorsal to the optic tract they turn in caudal direction and run parallel with and very close to the basal surface of the hypothalamus; individual fibers then turn medially to terminate in the external layer of the ME. Only a few fibers originate from the medial-ventral part of the PVN (medial pathway). These fibers run in ventral direction along the walls of the 3rd ventricle and terminate in the ME. Thus the majority of CRF fibers, similarly to other peptidergic systems, reach the medial basal hypothalamus from the anterolateral direction.

Adrenalectomy↗

PubMed1983

Corticotropin-releasing factor (CRF)-like immunoreactivity in the vertebrate endocrine pancreas.

The light microscopic immunocytochemical localization of corticotropin-releasing factor (CRF) is described in the endocrine pancreas of several species representing the major classes of vertebrates: fishes (channel catfish, Ictalurus punctatus), amphibians (African clawed toad, Xenopus laevis), reptiles (chameleon, Anolis carolinensis), birds (chicken, Gallus domesticus), and several mammals (rat, mouse, cat, rhesus monkey, and man). The CRF-containing cells are scattered over the entire islet tissue in primates and cat, whereas in rat and mouse they are located at the periphery of the islets. In the chicken and catfish, the CRF-containing cells are found in a central location within islets and form larger clusters or cords. Single cells with CRF-like immunoreactivity are interspersed between acinar cells of the exocrine pancreas in all species studied. The CRF cells show a substantial topographical overlap with glucagon cells, but their precise identity and function remain to be determined.

Animals↗