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Biomedical subjects

G Fink

Publications and source records attributed to G Fink.

At least 217 records · Page 12Linked to original sources

Oestradiol-17 beta increases the firing rate of antidromically identified neurones of the rat neostriatum.

Extracellular recordings were made from the neostriatum of rats anaesthetised with halothane. Normal male and female animals were used as well as castrated animals with implants containing oestradiol-17 beta (E2). In animals with high levels of circulating oestrogen, intact pro-oestrous rats and females and males bearing an E2 implant, individual units could be recorded that were spontaneously active and with axons that could be excited by stimulation in the crus cerebri. Such antidromically identified striato-nigral neurones were invariably silent in male animals and in ovariectomised females. In contrast to animals in pro-oestrus, intact female animals during metoestrus showed the 'male' pattern of striatal cell activity. These results show that E2 can stimulate spontaneous firing of striato-nigral neurons, and that this action of E2 is not sex-dependent.

Action Potentials↗

Endogenous GABA receptor ligands in hypophysial portal blood.

The concentrations of endogenous gamma-aminobutyric acid (GABA) receptor ligands were measured in hypophysial portal plasma by a sensitive and specific radioreceptor assay. Portal plasma contained higher concentrations of GABA receptor ligands than peripheral controls, although this increase was not due to authentic GABA but an unknown low-affinity ligand. Evidence is presented to support the hypothesis that the dipeptide homocarnosine may represent at least a part of this unknown. Electrical stimulation of median eminence evoked a massive (7.8-fold) increase in the rate of release of GABA (but not the low-affinity component) into portal blood. These results suggest that GABA and possibly other low-affinity ligands such as homocarnosine could serve as factors involved in the central control of anterior pituitary function.

4-Aminobutyrate Transaminase↗

A high molecular weight precursor of luteinizing hormone releasing hormone from rat hypothalamus.

A poly A+ enriched fraction of total RNA extracted from rat hypothalamus was translated in a messenger RNA-dependent cell free system from rabbit reticulocyte lysate supplemented with 3H-leucine. The translation products were immunoprecipitated using a specific antiserum to luteinizing hormone releasing hormone (LHRH). Following sodium dodecyl sulphate polyacrylamide gel electrophoresis and autoradiography of the immunoprecipitates, a single immunoreactive polypeptide was detected with an apparent molecular weight of 28,000. This is approximately twenty times larger than the active peptide, and thus suggests the presence of a high molecular weight precursor for the decapeptide, LHRH.

Animals↗

Prolactin measurements in normal and hypogonadal (hpg) mice: developmental and experimental studies.

Plasma and pituitary PRL levels are significantly greater in adult female than in male rats. This difference is thought to be brought about by ovarian steroids. We found a similar sex difference in pituitary PRL content in normal mice from 30 days of age. Ovariectomy reduced pituitary PRL content and this reduction was prevented by sc implants of estradiol-17 beta (E2). Implants of E2 also increased the pituitary PRL content in normal male mice to a level approaching that in normal females. The hypogonadal (hpg) mice did not show a sex difference in pituitary PRL content. Implantation of E2 into mutants of both sexes raised the pituitary content of PRL to the level in normal females. Treatment of intact but not ovariectomized hpg females with two injections/day of 6 micrograms FSH (NIH-FSH-S15) produced uterine growth and an increase in pituitary PRL content. Estrogen implants significantly increased plasma PRL concentrations in ovariectomized normal female and normal male mice but not in adult hpg male or female animals. These results show that elevation of the plasma E2 concentration increased significantly the synthesis of PRL in both normal and hpg mice of both sexes, and in the normal, but not the hpg mice, also increased the plasma concentration of PRL.

Aging↗

Thyrotropin-releasing hormone in rat pituitary stalk blood and hypothalamus: studies with high performance liquid chromatography.

Immunoreactive TRH (TRH-IR) in rat pituitary stalk blood and hypothalamus was investigated with high performance liquid chromatography in conjunction with a sensitive RIA. The TRH-IR of ethanol extracts of stalk blood resolved into three peaks, whether the blood was collected with the pituitary gland in situ or after the gland had been removed. The first peak corresponded to authentic TRH. By contrast, all the immunoreactive TRH in pituitary and hypothalamic extracts and in peripheral blood to which hypothalamic or synthetic TRH had been added eluted as a single peak with the same retention time as authentic TRH. The additional IR peaks in stalk blood did not correspond to known metabolites of TRH, and, since absent from the hypothalamus, they are unlikely to represent stored TRH precursors. Although authentic TRH constituted only 37% of total TRH-IR in pituitary stalk blood, the amount released during the first hour into stalk blood (1.7 ng) in relation to hypothalamic content (approximately 5 ng) was still high (approximately 34%) compared with that of LHRH (approximately 0.6%) and somatostatin (approximately 0.3%).

Animals↗

7. Corticosteroid secretion--clinical aspects. Plasma cortisol concentrations in the functional psychoses and Alzheimer type dementia: a neuroendocrine day approach in drug-free patients.

We have investigated the plasma concentration of cortisol in psychotic patients classified according to Feighner's criteria as either depressed, manic, schizophrenic or unclassified, and in 8 patients with Alzheimer's Type Dementia. The patients had been free of either neuroleptic or antidepressant drugs for at least 3 months before the study. Blood sampling was carried out by way of a "neuroendrocrine day" approach in which venous samples were taken at 07:00, 07:30 and 08:00 h; 15:00, 15:30 and 16:00 h; and 23:00, 23:30 and 24:00 h. This approach permits determination of circadian pattern of hormone release and allows for pulsatile hormone release. These preliminary results showed that, contrary to expectation, neither the mean concentrations nor the circadian pattern of plasma cortisol concentrations in patients with depression differed significantly from those in any other group.

Alzheimer Disease↗

Salmon calcitonin in lizard brain: a possible neuroendocrine transmitter.

Calcitonin is a polypeptide which until recently was thought to be concerned primarily with the control of body calcium. Recent studies carried out with radioimmunoassay have demonstrated the presence of this peptide in brain and we have carried out an immunohistochemical study showing the presence of high concentrations of calcitonin in the nerve varicosities and terminals of the hypothalamus and in particular the median eminence of the lizard Lacertus muralis. The distribution of this calcitonin, which cross-reacted with anti-salmon calcitonin, suggests that this polypeptide and/or its flanking peptides may function as a neuroendocrine neurotransmitter.

Animals↗

Immediate increases in plasma prolactin and neurophysin but not other hormones after electroconvulsive therapy.

Plasma prolactin, growth hormone, cortisol, luteinising-hormone-releasing hormone (LHRH), thyrotropin-releasing hormone (TRH), and nicotine and oestrogen stimulated neurophysin (NSN and ESN) were measured before and for 6 min after electroconvulsive therapy (ECT) in eight women with severe electroconvulsive therapy (ECT) in eight women with severe depression. Plasma concentrations of NSN and ESN had increased significantly (as much as 10-fold for NSN) within 1 min of the seizure, and concentrations of prolactin had increased within 2-4 min after the seizure. Whereas plasma prolactin and ESN either continued to increase or remained raised throughout the 6 min after seizure, the concentrations of NSN fell to reach a value at 6 min that was approximately 50% of the maximum. There were no increases in any of the other hormones or peptides within the 6 min period under study. Thus ECT has selective effects on hormone release which cannot be attributed simply to a generalised release of pituitary or hypothalamic hormones in response to brain stimulation and/or stress.

Adult↗

Sex difference in response to alphaxalone anaesthesia may be oestrogen dependent.

The steroid anaesthetic Althesin (Glaxo), which is a mixture of two C21 steroids, alphaxalone (3 alpha-hydroxy-5 alpha-pregnane-11, 20-dione--the active compound) and alphadolone acetate (21-acetoxy-3 alpha-hydroxy-5 alpha-pregnane-11, 20-dione), has been especially useful for the study of forebrain-autonomic and neuroendocrine functions. As determined by the loss of the righting reflex, Child et al. found no sex difference in the anaesthetic dose of Althesin administered intravenously (i.v.). However, in our neuroendocrine studies in which the anaesthetic was administered intraperitoneally (i.p.) and at dosage sufficient to produce surgical anaesthesia and analgesia, we observed a sex difference in the efficacy of Althesin. This may explain the difficulties that have been encountered in obtaining adequate anaesthesia (blockade of the somatomotor response to pain) with Althesin. Here we report, using cortical electroencephalography, that Althesin is a more potent anaesthetic than either sodium pentobarbitone or urethane, and that anaesthesia in the male rat requires about four times more Althesin (administered i.p.) than in the female. This sex difference is age dependent, can be abolished by administering oestrogen to the male, does not depend on sexual differentiation of the brain, and cannot be attributed to a sex difference in the metabolic clearance rate of alphaxolone. These results, taken together with those of Richards and Hesketh, suggest that the effect of alphaxalone may be mediated by interactions with synaptic membranes that are more specific than simply a generalized change in membrane structure, and that these interactions are affected by sex steroids.

Age Factors↗

Release of thyrotropin releasing hormone into hypophysial portal blood is high relative to other neuropeptides and may be related to prolactin secretion.

The amount of immunoreactive TRH released into hypophysial portal blood of female rats was about 2 orders of magnitude greater than gonadotropin releasing hormone and somatostatin. The turnover of TRH, as high as 80% of the total hypothalamic content per hour, was also much greater than that of any other known peptide. TRH release increased during the expected proestrous surge of prolactin and also in some animals during suckling.

Animals↗

Priming effect of luteinizing hormone releasing hormone in the hypogonadal mouse.

We have investigated the LH response to LH releasing hormone (LH-RH) in female hypogonadal (hpg) mice in which the hypothalamus contains no LH-RH and the pituitary gland contains significantly less LH than in normal mice. Both the releasing action and the priming effect of LH-RH were not significantly different in hpg compared with normal mice. Raised plasma concentrations of oestradiol-17 beta reduced pituitary responsiveness to LH-RH in normal but not in hpg mice. These results show that in the mouse neither long-term exposure to normal levels of LH-RH nor a normal pituitary content of LH are necessary for either the releasing or the priming action of LH-RH.

Animals↗

Effects of luteinizing hormone releasing hormone on the gonadotrophs of hypogonadal (hpg) mice.

Hypogonadal (hpg) mice lack hypothalamic luteinizing hormone releasing hormone (LH-RH); consequently the pituitary gonadotrophs, though differentiated, remain inactive. The acute and chronic responses of gonadotrophs in hpg mice to LH-RH to male hpg mice produced an eightfold increase in plasma LH after 5 min, but granule depletion was not detectable ultrastructurally. Vacuoles (300-600 nm) were present more frequently in gonadotrophs from hpg mice given LH-RH compared with control mice. Daily s.c. administration of 2 micrograms LH-RH to male hpg mice for 20 days stimulated a 63-fold increase in the pituitary content of FSH but only a twofold increase in the pituitary content of LH. Testicular weight increased fivefold but the weight of the seminal vesicles did not change. The frequency of cells immunoreactive for LH increased (x 1.6), the gonadotrophs hypertrophied (x 1.9) and the cell content of granules increased (x 2.3) to values close to the normal range. The rough endoplasmic reticulum and Golgi apparatus became more prominent. A striking result of long-term daily administration of LH-RH was the accumulation of large (1-2 micrometers) lipid droplets in about 40% of gonadotrophs. All these changes induced by LH-RH regressed towards the untreated hpg state when LH-RH administration wad discontinued for 5 and 10 days. These results show that the gonadotrophs of hpg mice can be stimulated trophically by LH-RH, and that long-term administration stimulates the synthesis and release of the gonadotrophins but the effect on FSH is much greater than on LH.

Animals↗