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Biomedical subjects

J T Cummins

Publications and source records attributed to J T Cummins.

At least 55 records · Page 3Linked to original sources
PubMed1986

Effects of ovine follicular fluid on plasma LH and FSH secretion in ovariectomized ewes to indicate the site of action of inhibin.

Ovariectomized ewes were given 2 ml s.c. injections of ovine follicular fluid (oFF) (N = 3) or serum (N = 3) and blood samples were collected each day for 3 days. Follicular fluid caused a significant (P less than 0.005) reduction in FSH within 1 day, but did not affect mean LH values. Two groups of 3 ewes were treated as above but sampled intensively (each 10 min for 6 h) on Days 1 (before treatment) and 4; mean plasma FSH concentration and plasma LH pulse frequency and amplitude were ascertained. Significant (P less than 0.005) reduction of FSH concentration was seen in the oFF-treated ewes. A non-specific reduction in LH pulse amplitude, but not pulse frequency, was noted in the control ewes. This experiment was repeated with 2 groups of 4 ewes that were conditioned to the experimental environment and effects on LH secretion were not observed in the controls given serum. Treatment with oFF caused a 70% reduction (P less than 0.005) in plasma FSH and a small (30%) but significant (P less than 0.005) reduction in mean LH concentrations. The latter was probably associated with a reduction in LH pulse amplitude in 3/4 animals (N.S.) with no change in LH pulse frequency. Treatment with oFF, as in Exp. 1, caused a 95% reduction in FSH values and significant (P less than 0.01) reduction (32%) of LH pulse amplitude in ovariectomized ewes that had been subjected to hypothalamo-pituitary disconnection and in which gonadotrophin secretion was reinstated with pulses of 250 ng GnRH every 2 h. These results suggest that proteins from the sheep follicular fluid, including inhibin, act at the pituitary level to inhibit FSH secretion and may have some effects on LH pulse amplitude.

Animals↗
PubMed1986

Effects of constant infusion of gonadotrophin-releasing hormone in ovariectomized ewes with hypothalamo-pituitary disconnection: further evidence for differential control of LH and FSH secretion and the lack of a priming effect.

Experiments were conducted in ovariectomized ewes after hypothalamo-pituitary disconnection (HPD) to examine LH and FSH secretion during constant infusion of gonadotrophin-releasing hormone (GnRH) or physiological saline and to determine whether or not a constant GnRH background enhances or diminishes pituitary responsiveness to GnRH pulses. Whereas pulsatile GnRH infusions maintained LH and FSH secretion, constant infusions (125 or 250 ng/h) led to the complete cessation of LH secretion and reduced FSH secretion. The rate of decline of plasma FSH concentrations was significantly (P less than 0.01) greater in animals receiving 250 ng GnRH/h than in saline-treated animals, whereas that in animals receiving 125 ng/h was not significantly different. When GnRH pulses were administered during constant GnRH infusion, the plasma LH pulse amplitudes were similar to those seen without the GnRH background. These data show that, in ovariectomized-HPD ewes FSH secretion does not require GnRH pulses and may merely reflect ongoing FSH synthesis and a constant low background of GnRH does not affect pituitary responsiveness to GnRH pulses.

Animals↗
PubMed1986

Transient increase in prolactin secretion following hypothalamo-pituitary disconnection in ewes during anoestrus and the breeding season.

Hypothalamic control of prolactin secretion was studied in ovariectomized ewes by comparing the effects of hypothalamo-pituitary disconnection (HPD) and sham-operation (sham-HPD). HPD caused a two-fold increase in plasma prolactin concentrations on days 1 and 7 following surgery during anoestrus and a tenfold increase during the breeding season. Thereafter, concentrations gradually declined to be similar to those in sham-HPD ewes by day 43 (breeding season) and day 145 (anoestrus). The maximum plasma prolactin response to HPD was similar during the two seasons (anoestrus: 128 +/- 15 bs breeding season: 118 +/- 13 micrograms/l). Sham-HPD had no effect on plasma prolactin concentrations. Prolactin pulse frequency was not affected by HPD, but increases in plasma prolactin concentrations were associated with increases in pulse amplitude. At the time of the normal anoestrus, plasma prolactin concentrations rose in both the HPD and sham-HPD ewes, raising the question of extra-hypothalamic regulation of seasonal changes in prolactin secretion. Plasma LH and FSH concentrations became undetectable in HPD ewes but were unaltered in sham-HPD ewes. We conclude that hypothalamic inhibition of pituitary prolactin secretion in the sheep can be demonstrated by HPD but that this effect is not sustained. This transience may indicate the additional requirement of hypothalamic-releasing factors in the control of prolactin release. In addition, the surgically isolated ovine pituitary of the HPD animal has an inherent pulsatile secretion of prolactin.

Anestrus↗
PubMed1986

Prolonged secretion of prolactin in response to thyrotrophin-releasing hormone after hypothalamo-pituitary disconnection in the ewe.

Surgical disconnection of the ovine hypothalamus from the pituitary gland (hypothalamo-pituitary disconnection; HPD) has provided a useful experimental model for studying the control of gonadotrophin secretion. The objective of the present study was to define the characteristics of prolactin secretion using stimuli acting through the hypothalamus or directly on the pituitary gland in HPD ewes. Prolactin responses to either a stressful stimulus or the dopaminergic antagonists metoclopramide (20 mg i.v.) or chlorpromazine (50 mg i.v.) seen in intact animals (sham-HPD) were completely abolished by HPD. Injection of TRH (100 micrograms i.v.) caused an immediate release of prolactin in both groups of ewes. In the HPD ewes plasma prolactin concentrations remained raised for at least 3 h after TRH injection, whereas in sham-HPD ewes prolactin concentrations began to decline after 20 min. Administration of bromocriptine (1 mg i.v.) 10 min after TRH inhibited the prolonged response to TRH in HPD ewes. The results support the hypothesis that prolactin exerts a short-loop feedback effect on its own secretion at the hypothalamic level.

Animals↗
PubMed1986

Induction of glutamate binding sites in hippocampal membranes by transient exposure to high concentrations of glutamate or glutamate analogs.

The number of Na+-independent, Cl--dependent glutamate binding sites in rat hippocampal membranes is increased two- to fourfold after pre-exposing isolated membranes or hippocampal slices to high concentrations (0.1-10 mM) of L-glutamate or of glutamate analogs with high affinity for this binding site, such as quisqualate, homocysteate, or aminoadipate. N-Methylaspartate and kainate are ineffective. A similar binding increase is induced by transient exposure to the dipeptide tyrosylglutamate. The newly induced binding sites appear to be identical with pre-existing Cl--dependent binding sites by several criteria: They have a similar pharmacological profile, they are sensitive to low concentrations of Na+, and the number of sites can be further increased by transient exposure to micromolar calcium concentrations. Moreover, binding of [3H]APB, a ligand selective for the Cl--dependent glutamate binding sites, is also increased after glutamate preincubation. The induction of binding sites by high glutamate concentrations, described herein, is calcium-independent, not inhibited by leupeptin and, therefore, different from the previously described activation of binding sites by a calcium-sensitive protease. The high concentration of ligand needed to induce increased binding suggests the presence in hippocampal membranes of a binding site with low, millimolar affinity that is functionally related to the known high-affinity binding sites. Several interpretations of the observed effects and their implications for the possible relationship between the binding site and the synaptic receptor are discussed.

2-Amino-5-phosphonovalerate↗
PubMed1985

Increased gonadotropin-releasing hormone pulse frequency associated with estrogen-induced luteinizing hormone surges in ovariectomized ewes.

Hypophyseal portal blood samples were taken from ovariectomized (OVX) ewes given 50 micrograms estradiol benzoate. This estrogen treatment elicited a biphasic alteration (decrease then increase) in LH secretion. During the negative feedback phase, pulsatile GnRH secretion continued; at this time the interpulse interval for the GnRH pulses (49.5 +/- 5.7 min, mean +/- SE, n = 6) was similar to that in 7 control OVX ewes (53.4 +/- 8.7 min). During the positive feedback phase the GnRH interpulse interval (26.8 +/- 9.8 min; n = 6) was significantly (P less than 0.05) less than in the controls. In 3/7 cases the GnRH pulse frequency in OVX controls was within the range observed for estrogen-treated sheep during the positive feedback phase. These data suggest that, in most cases, the LH surge that can be induced by estrogen in OVX ewes, is associated with an increased GnRH pulse frequency. In some animals the inherent GnRH pulse frequency may already be at a rate that is high enough to permit an LH surge by action of estrogen on the pituitary. In general, the mean concentrations of GnRH in portal blood during the LH surge were higher than those in untreated animals, suggesting an overall increase in GnRH output during the LH surge. Pulsatile GnRH secretion continues throughout the early negative feedback phase, suggesting that the predominant effect of estrogen at this time is at the pituitary level.

Animals↗
PubMed1985

GnRH pulse frequency determines LH pulse amplitude by altering the amount of releasable LH in the pituitary glands of ewes.

We have measured the size of the releasable pools of LH and FSH in the pituitary glands of ovariectomized ewes in which the pituitary was isolated surgically from the hypothalamus. The ewes were given GnRH pulses (250 ng) every hour (N = 3) or every 2 h (N = 3) for 1 week and then given a high dose GnRH infusion (0.5 micrograms/min) for 4 h. Blood samples were collected to characterize the LH and FSH responses to the GnRH pulses and infusion. The LH, but not FSH, responses to the individual GnRH pulses were pulsatile and the amplitudes of the LH pulses were greater in the sheep receiving pulses every 2 h. The sheep receiving hourly pulses showed lower LH responses to the high-dose infusions than did the sheep receiving pulses every 2 h. These data indicate a relationship between the amplitude of LH pulses and the size of the releasable pool of LH in the pituitary gland. As the frequency of GnRH pulses is decreased the amplitude of the LH responses is increased in direct proportion to the size of the releasable LH pool.

Animals↗
PubMed1984

Effects on plasma luteinizing hormone and follicle-stimulating hormone of varying the frequency and amplitude of gonadotropin-releasing hormone pulses in ovariectomized ewes with hypothalamo-pituitary disconnection.

The effects on luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion of various regimens of pulsatile gonadotropin-releasing hormone (GnRH) replacement were examined in ovariectomized (OVX) ewes after hypothalamo-pituitary disconnection (HPD). Hourly pulses of 500 ng GnRH restored gonadotropin secretion in OVX-HPD sheep. Replacement beginning 2 days after HPD gave consistent responses of LH and FSH within a week. Replacement beginning 61-96 days after HPD caused more gradual re-establishment of LH and FSH secretion with LH responses appearing immediately and FSH responses appearing 2 weeks later. When hourly GnRH pulses were increased in amplitudes from 250 to 500 ng the plasma LH baseline, peak values and pulse amplitudes were increased. There was no significant change in plasma FSH levels over 10 pulses at the higher dose. Decreases in GnRH pulse frequency led to increases in LH pulse amplitude and decreases in plasma LH baseline. In contrast, immediately after a change from a 2-hourly to an hourly mode, an increase in LH baseline occurred without an immediate reduction in LH pulse amplitude. Mean plasma FSH concentrations increased when the frequency was reduced from hourly to 2-hourly or 4-hourly. However, a change from 4-hourly to hourly pulses did not reduce FSH values within 7 days. It is concluded that changes in the pattern of LH secretion observed during the ovine estrous cycle could be accounted for, in part, by changes in GnRH pulse frequency.

Animals↗
PubMed1984

Direct pituitary effects of estrogen and progesterone on gonadotropin secretion in the ovariectomized ewe.

The direct pituitary effects of estrogen and progesterone on the secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were studied in ovariectomized (OVX) ewes in which the pituitary had been disconnected surgically from the hypothalamus (hypothalamo-pituitary disconnection, HPD). Gonadotropin secretion was restored with hourly pulses of 500 ng gonadotropin-releasing hormone (GnRH) via intra-atrial cannulae. Intramuscular injections of 50 micrograms estradiol benzoate (EB) to 5 sheep initially caused reductions (approximately 50%) in plasma LH baseline, peak values and LH pulse amplitude. Thereafter all parameters of plasma LH concentration increased 2- to 3-fold above starting values. After these 5 sheep had received 2 subcutaneous progesterone implants (mean +/- SEM plasma levels 5.3 +/- 1.5 nmol/l), the biphasic LH response to EB was still apparent and increases in LH peak values (267 +/- 19%) and LH pulse amplitudes (262 +/- 23%) were greater (p less than 0.05) than those seen with EB alone (195 +/- 11 and 172 +/- 14%, respectively). The presence of 2 progesterone implants alone did not change plasma LH baseline, peak values or pulse amplitude, or plasma FSH values. In the second experiment, where 4 OVX-HPD ewes were given 4 progesterone implants (plasma progesterone 27.7 +/- 3.4 nmol/l), there were no effects on basal plasma LH or plasma FSH values. The LH responses to EB were more marked in 4 OVX-HPD ewes given 4 progesterone implants than in the animals given EB alone. Also, the estrogen-induced LH surge occurred earlier in the ewes given 4 progesterone implants than in those given estrogen alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Pituitary gland function after disconnection from direct hypothalamic influences in the sheep.

A surgical procedure is described for isolating the pituitary gland from hypothalamic influences in sheep. The procedure results in total deafferentation of the stalk and median eminence but maintains the blood supply to the pituitary gland. The median eminence, pituitary stalk and anterior face of the pituitary gland were exposed by a transnasal, transphenoidal approach. In early studies section of the pituitary stalk as close as possible to the pituitary gland caused almost total infarction of the gland. Attempts were made to disconnect the pituitary gland from the hypothalamus by section immediately above the lateral inputs of the superior hypophyseal arteries but variable results were obtained, always with infarction of part of the pars distalis. When the pituitary gland was disconnected from the hypothalamus by entering the median eminence above the portal circulation and evacuating the nervous tissue of the tuber cinereum, (hypothalamo-pituitary disconnection; HPD), a small area of infarction was found in the pars distalis of only 1/10 cases. HPD effectively disconnected the pituitary gland from hypothalamic control whilst the pars distalis was not deprived of its blood supply. Complete severance of hypothalamo-pituitary connections also caused atrophy of the pars nervosa and enlargement of the cells of the pars intermedia. Following HPD, plasma LH and FSH concentrations diminished and plasma prolactin concentrations rose. On the day after surgery there were no LH, FSH or prolactin responses to 50 micrograms (i.m.) of oestradiol benzoate indicating the functional isolation of the pituitary gland from the hypothalamus. The isolated pituitaries were capable of responding to gonadotropin releasing hormone by LH release. Disconnection of the pituitary gland from the hypothalamus by subpial deafferentation provides a good in vivo isolated pituitary model in the sheep.

Animals↗
PubMed1983

Regional effects of ethanol on glutamate levels, uptake and release in slice and synaptosome preparations from rat brain.

Chronic ethanol treatment effects a decrease in K+-stimulated endogenous glutamate release and an increase in glutamate levels in rat frontal cortex. This treatment also increases (3H)-glutamate uptake in striatal and hippocampal slices. No uptake changes were observed in either cortical slices or synaptosomes. Ethanol withdrawal increases K+-stimulated glutamate release in cortex and hippocampus and glutamate levels in cortex, striatum and hippocampus. (3H)-glutamate uptake is increased in striatum of withdrawn animals. Thus, regional variations were observed with regard to both effect and degree of effect. Because in vitro and acute ethanol treatments had no effect on uptake or release, these changes probably result from activated feedback mechanisms that attempt to compensate for ethanol's action on brain systems rather than direct effects on membrane structure. Combined level-release data suggest an effect of ethanol on glutamate distribution in cortex and striatum. Combined uptake and release data indicate a correlation between diminished glutamate synaptic activity and the addicted state, and between heightened glutamate synaptic activity and the withdrawn state.

Alcohol Drinking↗
PubMed1982

Microscopic observations on endogenous fluorochromes within a nerve fibre excited by a 325 nm He-Cd laser.

A microscopic procedure to observe endogenous fluorochromes in superfused tissues is described. In this procedure, a 325 nm beam from a He-Cd laser is directed through the objective lens of a microscope onto the surface of a brain slice. Fluorescent structures within the tissue can be observed, photographed and measured. A nerve fibre running from the corporis callosi to the dorsal cerebral cortex was studied with this approach. The 325 nm laser beam excited material with an emission peak at 420 nm within a fibre on the cut surface of a rat brain slice superfused with Krebs-Ringer. A similar fibre was observed in vivo in the exposed mouse brain. Packets of the fluorescent material appear to move within the fibre in vitro. The fluorescence of the fibre was rapidly diminished by cyanide, colchicine, rotenone and the withdrawal of Ca2+. Elevation of [K+] in the superfusate caused a "haloing' of the fibre's granularity without decreasing the total fluorescence. This phenomenon is possibly related to the depolarization by [K+] of neurones. Although the structure of the fluorochrome was not established, it is suggested that it may be a neurotransmitter-related substance undergoing axonal movement.

Animals↗
PubMed1982

Effect of chronic ethanol treatment and withdrawal on mitochondrial redox activity in brain cortical slices.

The effect of chronic ethanol treatment on cytochrome a-a3 redox activity was studied in rat brain cortical slices. The slices were depolarized by electrical pulses and the level of reduced cytochrome a-a3 was directly measured within the slice by dual wavelength spectrometry. Cortical slices cut from the brains of rats withdrawn from ethanol demonstrated less reduction of cytochrome a-a3 following electrical depolarization compared both to controls and ethanol addicted rats. It is suggested that this effect of ethanol withdrawal on cytochrome a-a3 redox activity is due to a change in the regulation of mitochondrial activity.

Alcoholism↗
PubMed1981

Effects of low ammonia levels on NAD(P)H levels and glutamate secretion during calcium-dependent depolarization of CNS slices.

Simultaneously with an evoked release of endogenous glutamate, redox changes in NAD(P)H levels occur as a response to electrical or chemical stimulation of the isolated CNS tissue. While electrical-field stimulation induces a transient increase in tissue NAD(P)H, KCl stimulation produces a decrease in NAD(P)H. One possible interpretation for this difference is that elevated KCl induced glutamate release from larger cell populations, including glia, while electrical stimulation might have a more neuro-specific action. In the present report, it is shown that the electrically or biochemically evoked release of endogenous glutamate is strongly inhibited by ammonium ions at 3--5 mM in the hippocampus and frontal cortex. At the same time, ammonium ions inverted the NAD(P)H response of the tissue during electrical stimulation, making both electrical and KCl depolarization induce a decrease in NAD(P)H. There was no effect of ammonium ions per se on the NAD(P)H levels, and to obtain the effects on both NAD(P)H and glutamate release, the tissue had to be exposed for 40--60 minutes to ammonium ions. The results are interpreted to indicate that ammonium ions influence regulatory control mechanisms in cell populations in the tissue slice that secretes glutamate in response to depolarization.

Ammonia↗
PubMed1981

L-Proline inhibition of glutamate release.

The influence of 1 mM-L-proline on electrically stimulated release of endogenous glutamate from slices of rat frontal cortex was measured. One mM-L-proline approximates the in vitro concentration that inhibits glutamate-induced spreading depression. Also, this L-proline level has been reported to be present in brain after an intraperitoneal injection that induced amnesia in chicks. L-Proline but not D-proline exhibits an inhibitory effect on glutamate release, thus supporting the suggestion that this mechanism may play a role in memory retention and/or formation.

Animals↗
PubMed1980

Identification of harman in the rat arcuate nucleus.

This communication describes the presence of 1-methyl-beta-carboline (harman) in the hypophysiotropic area of the hypothalamus which incorporates the arcuate nucleus. Diethyl ether extracts of borate-buffered arcuate homogenates were subjected to silica column chromatography and thin-layer chromatography (TLC). Identification of the beta-carboline was accomplished by use of fluorescent spectrometry, gas chromatography (GC), mass spectrometry (MS) and combined gas chromatography-mass spectrometry (GC-MS).

Alkaloids↗
PubMed1980

Cyclic AMP enhancement of depolarization-induced NAD(P)H changes in brain cortical slices.

The increased levels of NAD(P)H effected by electrical depolarization are markedly augmented in the presence of cyclic AMP, isoproterenol, or RO 20-1724, agents known to elevate cyclic AMP in rat brain slices. The data presented indicate that the cyclic AMP effect on an important component of intermediate metabolism is not an enhancement of a basal response but a separate response that is activated by depolarization, is Ca2+-dependent, regulates cytochrome a-a3 independently of its effects on NAD(P)H levels, and is dependent on a substrate other than glucose.

Animals↗