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Biomedical subjects

C Kordon

Publications and source records attributed to C Kordon.

At least 145 records · Page 8Linked to original sources
PubMed1982

Somatostatin receptors on rat anterior pituitary membranes.

[125I]Iodo-Tyr1-somatostatin (SRIF) binds with high affinity to one class of sites in the rat anterior pituitary with a KD of 0.91 +/- 0.22 nM and a receptor concentration of 104.4 +/- 1.9 fmol/mg protein. This binding is saturable with respect to tissue concentration and is time-, temperature-, pH-, and calcium-dependent. It is also reversible as a function of time. The rates of association and dissociation were calculated to be 5.98 X 10(7) M-1 min-1 and 0.578 min-1, respectively. Binding of [125I]iodo-Tyr1-SRIF is not inhibited by morphine, beta-endorphin, [D-Ala2]Met-enkephalin, LHRH, TRH, histidylproline diketopiperazine, neurotensin, substance P, bombesin or vasoactive intestinal peptide. In contrast SRIF, [Tyr1]SRIF, and [D-Trp8,D-Cys14]SRIF displace [125I]iodo-Tyr1-SRIF binding with Ki values 0.10 +/- 0.05, 0.46 +/- 0.18, 0.05 +/- 0.01 nM, respectively. The constants of inhibition of a series of alanine monosubstituted analogs of SRIF are correlated (r = 0.89) with their biological potency on GH secretion. Furthermore, postnatal development patterns of [125I]iodo-Tyr1-SRIF binding sites follow the ability of SRIF to inhibit GH release. Thus, [125I]iodo-Tyr1-SRIF binding to adenohypophyseal membranes seems to reflect interaction with SRIF receptors on adenohypophyseal cells. Since biological effects of the peptide have been reported on GH, thyrotropin-stimulating hormone, and PRL secretion, further studies are required to determine the cell types upon which this binding occurs.

Animals↗
PubMed1982

Reciprocal interactions of somatostatin with thyrotropin-releasing hormone and vasoactive intestinal peptide on prolactin and growth hormone secretion in vitro.

Reciprocal interactions of somatostatin (SRIF) and vasoactive intestinal peptide (VIP) or TRH on in vitro PRL and GH release from male rats hemipituitaries were investigated. SRIF did not modify basal PRL release, but TRH- or VIP-induced release was inhibited by SRIF in a dose-dependent manner [effective concentration-fifty (EC50) = 1.7 +/- 0.9 nM for SRIF inhibition of TRH stimulation and EC50 = 0.8 +/- 0.5 nM for SRIF inhibition of VIP stimulation]. VIP and TRH did not affect GH release by themselves, but reduced the inhibition of GH secretion elicited by SRIF (EC50 = 7.6 +/- 3.4 nM for TRH blockade of SRIF inhibition and EC50 = 4.6 +/- 3.1 nM for VIP blockade of SRIF inhibition). Secretin, a partial structural analog of VIP, also blocked SRIF-induced inhibition of GH and stimulated PRL release. Secretin stimulation of PRL release was also prevented by SRIF. [D-Trp8,D-Cys14]SRIF, a potent analog of SRIF, antagonized VIP stimulation of PRL secretion with the same apparent affinity as the native peptide. The maximal stimulation, but not the apparent affinity of VIP action on prolactin release was reduced by SRIF, suggesting that the interaction is of a noncompetitive nature. This conclusion as further substantiated by the observation that neither TRH nor VIP were able to displace specific 125I-labeled [Tyr1] SRIF high affinity binding to pituitary membranes. The three peptides tested thus appear to exhibit reciprocal interactions mediated by independent receptor sites on GH as well as on PRL-producing cells.

Animals↗
PubMed1982

Interaction of beta-adrenergic agonists and antagonists with the stimulation of growth hormone release induced by clonidine or by morphine in the rat.

The beta-adrenergic agonist, isoprenaline, and antagonist, propranolol, had no effect on the delayed basal secretion of GH consistently observed in rats treated with the narco-analgesic gamma-hydroxybutyrate. Under the same experimental conditions, GH release was distinctly stimulated by infusion of the alpha-adrenergic agonist, clonidine, and by morphine; both responses were dose-dependent. The effects of beta-adrenergic agonists and antagonists on these GH responses were as follows: in rats pretreated with isoprenaline -the GH release induced by clonidine and morphine was abolished whereas it was enhanced in rats pretreated with propranolol. These data confirmed and extended previous reports from this laboratory on the inhibitory role of beta-adrenergic receptors on GH regulation.

Animals↗
PubMed1981

Topography of median eminence somatostatinergic innervation.

Somatostatin (SRIF) in the central nervous system is mostly concentrated in the median eminence (ME). Immunocytochemical methods have revealed high densities of SRIF-positive perikarya between the preoptic area and the periventricular nucleus of the hypothalamus (NPE). The aim of the present study was to define more precisely the specific pathways of SRIF neurons from NPE to the ME. SRIF levels were measured by radioimmunoassay, following various hypothalamic transections. Frontal periventricular sections decreased SRIF-ME content by 70% (P less than 0.01), when located at the anterior end of the ME but no diminution was observed when the cuts were located anteriorly or posteriorly. Parasaggital transections decreased SRIF-ME levels by 50% (P less than 0.05) when located at the outer border of the ventromedial and premammillary nucleus, but the decrease was not significant when cuts were located anteriorly. Taken together, our data indicate that most SRIF-containing neurons, originating in the NPE, do not reach the ME directly along the border of the 3rd ventricle; instead they form a loop across the medial forebrain bundle before re-entering the mediobasal hypothalamus at the ME level.

Afferent Pathways↗
PubMed1981

Noradrenaline stimulates somatostatin release from incubated slices of the amygdala and the hypothalamic preoptic area.

Neurotransmitter effects were studied on in vitro release of immunoreactive somatostatin (SRIF) from slices prepared from several regions of the rat brain: mediobasal hypothalamus (MBH), preoptic anterior hypothalamic area (POA) and amygdaloid complex (AMY). Potassium (K+, 56 mM) stimulated SRIF release in all structures tested in a calcium dependent manner. Morphine, dopamine, GABA and serotonin did not modify SRIF release in any structure; noradrenaline (NA) was not effective on MBH slices, but elicited a dose-dependent stimulation of SRIF release from POA and AMY (ED50 = 6.4 +/- 1.4 nM and 3.6 +/- 1.2 nM respectively). Converse orders of potency of adrenergic agonists were observed in both structures (POA, adrenaline greater than noradrenaline greater than isoproterenol; AMY, isoproterenol greater than adrenaline greater than noradrenaline). Phentolamine blocked NA-induced SRIF release in the POA while propranolol was ineffective. On the contrary, propranolol, but not phentolamine, antagonized NA stimulation in the amygdala. The data suggest that NA acting through specific receptors modulate SRIF release from POA and AMY. In POA, NA effect seems mediated through alpha adrenergic receptors while in AMY, beta receptors are involved. The possibility that these interactions of NA with SRIF release are correlated with effects of NA on growth hormone secretion or on epileptic events is discussed.

Amygdala↗
PubMed1981

Long lasting effects of intrauterine growth retardation of 5-HT metabolism in the brain of developing rats.

Intrauterine growth retardation (IUGR) was achieved by ligating the artery and vein supplying one uterine horn in pregnant rats on the 5th day before delivery. At birth, the weight of the whole body and of the forebrain (but not that of the brain stem of about half of the offspring) were significantly lower than those of normal controls. This deficit persisted for at least the first 3 postnatal weeks. During the immediate period following birth, the concentrations of norepinephrine, dopamine, serotonin and 5-hydroxyindoleacetic acid (5-HIAA) were significantly higher in IUGR rats than in controls. Increased levels of serotonin and 5-HIAA were still observed in the forebrain and brain stem of 15-day-old IUGR rats and were associated with parallel increases in brain and serum free tryptophan levels. These results indicate that a transient insult in the fetal life could result in long-lasting alterations in 5-HT metabolism in CNS of developing rats.

Animals↗
PubMed1981

Occurrence of higher molecular forms of LHRH in fractionated extracts from rat hypothalamus, cortex and placenta.

Separation of higher molecular forms of LHRH-like immunoreactive material was attempted in homogenates and subcellular fractions of hypothalamus, cerebral cortex and placenta. Physiological activity was checked by means of antibodies directed against different sequences of LHRH and shown to recognize synthetic LHRH analogs extended on either C- or N-terminal portions of the molecule. After molecular-sieve filtration, 2 peaks of immunoreactive material corresponding apparently to sequences of LHRH extended on the C terminus were recovered. Peak I, with a molecular weight of about 26 000 dalton, was found exclusively in a cytoplasmic and axoplasmic supernatant (S2), where it migrated alone with microsomes. Peak II (1800 dalton) was present both in S2 and in a synaptosomal fraction (P2) corresponding to nerve endings. Native LHRH was almost exclusively recovered from the synaptosomal fraction. Extracts from placenta or cerebral cortex contained little or no native LHRH; in contrast, a small amount of immunoreactive material corresponding to peak II was detected in the cerebral cortex, and fairly large amounts of both putative precursors were found in the placenta. Chromatography of tissues containing no LHRH, such as cerebellum or liver, yielded no immunoreactive material at either elution site, thus suggesting specific detection of LHRH-like material under our experimental conditions. The present data suggest that 2 higher molecular forms, one slightly heavier than the native peptide itself, and another corresponding to a much larger protein, could represent LHRH precursors and are present in the hypothalamus as well as the cerebral cortex and the placenta.

Animals↗
PubMed1981

Importance of perinatal testosterone in sexual differentiation in the male rat.

Testosterone secretion in the male rat was high during the late fetal and immediate postnatal periods. It then showed a rapid decrease 3h after birth and remained low until puberty. Male rats from mothers given daily injections of an antibody to testosterone during the week before delivery displayed an LH peak when they were adult, orchidectomized and implanted with oestradiol. However, the amplitude of the peak was far smaller than in female rats from the same mothers treated in the same manner. Thus, the critical period during which testosterone triggers hypothalamic sexual differentiation is very close to birth, possibly starting at the end of the fetal period.

Animals↗
PubMed1981

[PRF activity of VIP in vitro (author's transl)].

The effect of VIP on prolactin secretion from incubated rat hemipituitaries was characterized. Under these conditions, the secretion of GH, LH, FSH, ACTH was not affected, indicating that the effect of VIP is hormone specific. The stimulation of prolactin was dose-dependent, with an apparent affinity of VIP of 10.9 +/- 3.1 nM and a maximal stimulation of 57.7 +/- 4.2%. Secretin, a structurally related peptide, was also active at higher concentrations, whereas another partial analogue, glucagon, was ineffective. Furthermore, VIP does not act through pituitary DA receptors since alpha-flupentixol, a potent dopaminergic antagonist, does not block the stimulation of prolactin secretion by VIP. In addition, stimulation by VIP and TRH was additive. Naloxone and met-enkephalin were ineffective on the VIP effect on prolactin release. In contrast, SRIF seems to inhibit the VIP stimulation of prolactin release. Our data suggest that VIP, which was found in the hypothalamo-hypophyseal blood at concentrations of the same order of magnitude as that found to stimulate PRL in vitro, could be a physiological PRF.

Animals↗
PubMed1981

Long lasting effects of intrauterine malnutrition on neurotransmitters metabolism in the brain of developing rats.

Intrauterine growth retardation (IUGR) was achieved by ligating the artery and vein supplying one uterine horn in pregnant rats on the 5th day before delivery. At birth, the weight of the whole body and of the forebrain (but not that of the brain stem of about half of offspring) were significantly lower than those of normal controls. This deficit persisted for at least the first 3 postnatal weeks. During the immediate period following birth, the concentrations of norepinephrine, dopamine, serotonin and 5-hydroxyindoleacetic acid (5-HIAA) were significantly higher in IUGR rats than in controls. Increased levels of serotonin and 5-HIAA were still observed in the forebrain and brain stem of 15-day-old IUGR rats and were associated with parallel increases in brain and serum free tryptophan levels. These results indicate that a transient insult in the fetal life could result in long-lasting alterations in 5-HT metabolism in the CNS of developing rats.

Animals↗
PubMed1981

Serotonin and the regulation of pituitary hormone secretion and of neuroendocrine rhythms.

The importance of 5-HT synaptic transmission for induced or cyclic activation of pituitary secretion now seems widely agreed upon. Raphe structures, the suprachiasmatic nucleus, and, hypothetically, identified mesencephalic 5-HT containing neurons can be assumed to represent parts of the neuronal circuitry of a central clock which synchronizes neuroendocrine rhythms. Cyclic input from the pineal gland may also be involved, though the meaning of this has not yet been clearly established. The primary role of the transmitter may be to modulate transmission to neurosecretory neurons at the output of this clock. This modulation is not hormone-specific and affects, simultaneously, several endocrine functions. 5-HT has also been shown to facilitate the pituitary response to discrete neuroendocrine reflexes, such as the suckling-induced release of prolactin. 5-HT interactions with hormone control provide a good illustration of the neuromodulatory role of the amine.

Animals↗
PubMed1980

Interaction of the anti-estrogen CI-628 and estradiol on plasma LH and hypothalamic LH-RH in the female rat.

The effects of the anti-estrogen Ci-628 have been tested on both plasma LH and hypothalamic LH-RH content in ovariectomized or ovariectomized, estradiol (E2)-implanted rats, in order to correlate those parameters with the [3H]E2 retention in the hypothalamus and the pituitary. Incresing doses of CI-628 induced a dose-dependent inhibition of [3H]E2 retention in both cytosolic and nuclear fractions of the pituitary. In contrast, hypothalamic retention of [3H]E2 is only inhibited significantly with higher doses of CI-628 (2.4 and 24 mg/kg). In ovariectomized rats, only a high dose of CI-628 (24 mg/kg) is able to decrease elevated LH levels observed following castration. In the presence of E2, CI-628 has both estrogenic and anti-estrogenic properties on LH secretion. CI-628 acts at the pituitary level to decrease the tissue sensitivity to LH-RH, but has no effect on mediobasal hypothalamic (MBH) LH-RH content.

Animals↗