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Biomedical subjects

P L Taylor

Publications and source records attributed to P L Taylor.

At least 19 recordsLinked to original sources
PubMed1992

Molecular cloning and characterisation of the rat pituitary gonadotropin-releasing hormone (GnRH) receptor.

We have isolated the gonadotropin-releasing hormone receptor (GnRH-R) from a rat anterior pituitary cDNA library, determined its sequence and demonstrated receptor function. The 2.2 kb rat GnRH-R clone encodes a protein of 327 amino acids. A 1.3 kb clone encoding the mouse GnRH-R has previously been described (Tsutsumi et al., 1992). Although both the mouse and rat protein share significant homology with molecules belonging to the family of G protein-coupled receptors, they have certain unusual features, an example being the complete absence of a COOH terminal tail. The 3'-untranslated region reported missing in the mouse is present in the rat cDNA, where an extended 1 kb of 3'-untranslated region extending to the poly-A tail is shown. At the amino acid level, the rat GnRH-R shows considerable homology with that of the mouse. Electrophysiological studies with Xenopus oocytes and transfection of the cDNA into COS-1 cells, have shown that the 2.2 kb cDNA clone encodes a functional receptor.

Action Potentials↗
PubMed1991

Cloning, sequencing and tissue distribution of a candidate G protein-coupled receptor from rat pituitary gland.

A new member of the family of G protein-coupled receptors has been isolated from a rat pituitary cDNA library by the polymerase chain reaction (PCR) using degenerate oligonucleotide primers. The corresponding protein sequence shows seven transmembrane domains and contains conserved regions of homology characteristic of the G protein-coupled class of receptors. The novel receptor mRNA is expressed in the brain, pituitary gland and testis, and has been localized by in situ hybridization in discrete regions of the brain. Expression of the receptor mRNA in Xenopus oocytes and in transfected mammalian cells has not yet permitted identification of the corresponding ligand for this receptor.

Amino Acid Sequence↗
PubMed1990

Nonuniform irradiation of the canine intestine. II. Dosimetry.

An experimental model has been developed for quantitative studies of radiobiological damage to the canine small intestine following partial-body nonuniform irradiation. Animals were irradiated with 60Co gamma rays to simulate the nonuniform irradiation which do occur in victims of radiation accidents. The model used a short source-to-surface distance for unilateral irradiations to produce a dose gradient of a factor of two laterally across the canine intestinal region. The remainder of the animal's body was shielded to prevent lethal damage to the bone marrow. In situ dosimetry measurements were made using thermoluminescent dosimeters to determine the radiation dose delivered as a function of position along a segment of the small intestine. This system made it possible to correlate the radiation dose delivered at a specific point along the small intestine with the macroscopic and microscopic appearance of the intestinal mucosa at that point, as determined by direct observation and biopsy using a fiberoptic endoscope. A key feature of this model is that dosimetry data for multiple sites, which receive a graded range of radiation doses, can be correlated with biological measurements to obtain a dose-response curve. This model is being used to evaluate the efficacy of new therapeutic procedures to improve survival following nonuniform irradiation.

Accidents↗
PubMed1989

Chloride channels mediate the response to gonadotropin-releasing hormone (GnRH) in Xenopus oocytes injected with rat anterior pituitary mRNA.

Functional expression of receptors for GnRH was studied using Xenopus laevis oocytes injected with poly(A)+ mRNA extracted from rat anterior pituitary glands. Whole-cell currents were monitored using two-electrode voltage-clamp techniques. In oocytes which responded to both GnRH and TRH, the GnRH response showed a longer latency and time-to-peak than the TRH response. The response to GnRH or an agonist of GnRH receptors, buserelin (1 nM-1 microM) consisted of current fluctuations and occurred in a dose-dependent manner. This GnRH response was blocked by the Cl- channel blockers 9-AC (9-anthracene carboxylic acid; 1 mM), 4,4'-diisothiocyanastilbene-2,2'-disulfonic acid (0.1 mM), and diphenylamine-2-carboxylic acid (0.1 mM). The reversal potential for the GnRH-induced current fluctuations was -25 mV, comparable with the reported Cl- equilibrium potential in Xenopus oocytes, and its shift, when the external concentration of Cl- was changed, was reasonably described by the Nernst equation. These results indicate that the GnRH-induced response was dependent on the activity of Cl- channels. Ca2+ also plays a role, as the GnRH-induced response was reversibly suppressed by a calmodulin inhibitor, chlordiazepoxide (0.2 microM), and by a blocker of intracellular Ca2+ release, TMB-8 (8-(N.N-diethylamino) octyl-3,4,5-trimethoxybenzoate; 0.1-0.2 mM). It is concluded that GnRH (and TRH) receptors, expressed in Xenopus oocytes by injecting exogenous mRNA from rat anterior pituitary glands, operate via activation of Ca2+-dependent Cl- channels.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1989

LHRH pulse frequency in normal and infertile men.

The aim of this study was to examine the hypothesis that decreased LHRH pulse frequency may be responsible for the preferential rise in FSH in infertile men. The LH pulse pattern was determined as an index of hypothalamic LHRH secretion in 21 infertile patients with idiopathic azoospermia or oligoasthenozoospermia and 14 fertile age-matched controls by frequent blood sampling at 10-min intervals for 24 h. The infertile patients were further divided into three groups according to their relative concentrations of FSH and LH: (1) normal FSH and LH, (2) raised FSH but normal LH, and (3) raised FSH and LH. LH pulses were detected by a computerized algorithm (Munro) validated against a threshold method. Concentrations of FSH, testosterone, sex hormone-binding globulin and oestradiol were measured in pooled plasma. Luteinizing hormone pulse frequencies in normal men were not significantly different from the infertile group as a whole. Similarly, mean LH pulse frequencies in infertile subgroups 1, 2 and 3 were not significantly lower than normal. Pulse interval, however, was increased in subgroup 1 compared with normal. Mean 24 h LH in group 2 was significantly higher than normal, but still within the normal range. The total testosterone, but not the free testosterone index was significantly decreased in the infertile group compared with normal. There was no correlation between mean FSH and LH pulse frequency or interval. In conclusion, our results show that in patients with seminiferous tubular dysfunction, the typical pattern of raised plasma FSH, increased LH pulse amplitude, raised FSH: LH ratio and normal or marginally low testosterone was not associated with any significant deviations in LHRH pulse frequency from the range observed in normal fertile men. This is not compatible with the hypothesis that decreased LHRH pulse frequency is associated with or the cause of the preferential rise in FSH in men with idiopathic infertility. Thus unlike anovulatory infertility in females, functional defects of hypothalamic LHRH secretion remain an uncommon finding in male infertility. Attempts to treat idiopathic oligozoospermia by altering LHRH pulse frequency is therefore unlikely to yield any clinical benefit.

Adult↗
PubMed1988

Functional expression of rat pituitary gonadotrophin-releasing hormone receptors in Xenopus oocytes.

Expression of receptors for the hypothalamic regulatory peptide, gonadotrophin-releasing hormone (GnRH), was investigated by intracellular recording from Xenopus oocytes injected with poly(A)+ mRNA isolated from rat anterior pituitary glands. Membrane depolarizations were induced in oocytes in a dose-dependent fashion following the application of GnRH (10nM - 1 microM) or a GnRH superactive agonist, buserelin (1nM - 1 microM). The response was reversibly blocked by the addition of a GnRH antagonist (1 microM). TRH (10nM - 1 microM) had no effect on most of these oocytes. In contrast, some other oocytes which showed no responses to GnRH or to the GnRH agonist, displayed depolarizing responses to TRH (10nM - 1 microM). A relatively small number of oocytes responded to both ligands. Control oocytes did not respond to the GnRH analogues or to TRH. This successful expression of the GnRH receptor could provide a new approach to the study of the receptor, and serve as a means for the isolation and cloning of the encoding genes.

Animals↗
PubMed1987

LHRH and beta-endorphin in the hypothalamus of the ram in relation to photoperiod and reproductive activity.

The regional distribution and relative concentrations of LHRH and beta-endorphin immunoreactivity in the hypothalamus were compared in sexually active and sexually inactive Soay rams. LHRH was localized principally in the medial basal hypothalamus and median eminence with lower concentrations in the anterior hypothalamus and preoptic area. beta-endorphin immunoreactivity was also found in highest concentrations in these regions but was more widely distributed into the rostral, dorsal and lateral parts of the hypothalamus. LHRH content in the medial basal hypothalamus was significantly lower in the sexually active rams compared to inactive rams while there was no difference in beta-endorphin immunoreactivity content between the two groups. Gel filtration chromatography of hypothalamic extracts revealed that the beta-endorphin immunoreactivity was due to both beta-lipotropin and beta-endorphin; the ratio of beta-endorphin: beta-lipotropin tended to be less in the sexually active rams than in the sexually inactive rams. The results are consistent with the hypothesis that beta-endorphin is a physiologically important endogenous opioid involved in the modulation of LHRH secretion.

Animals↗
PubMed1987

Effect of small doses of bovine follicular fluid on the tonic secretion of gonadotrophins in the ewe.

Previous work has shown that treatment of ewes with steroid-free bovine follicular fluid (bFF), a rich source of inhibin, partially inhibits the increase in mean plasma concentrations of LH induced by ovariectomy. The present experiment was designed to test the hypothesis that this effect was a reflection of reduced LH pulse amplitude which would only be expressed at high (pharmacological) doses of bFF. To do this, we assessed the dose-response to bFF of the secretion of FSH and LH pulses in intact and acutely ovariectomized ewes. In intact ewes, a low dose of bFF (0.2 ml s.c. every 8 h) had no detectable effect on the secretion of FSH, an intermediate dose (0.6 ml s.c. every 8 h) depressed FSH concentrations for about 24 h and a high dose (1.8 ml s.c. every 8 h) reduced FSH concentrations to undetectable levels. In ewes treated with 1.8 ml bFF, FSH concentrations also remained undetectable after ovariectomy and did not increase until treatment was withdrawn. In ewes treated with 0.6 ml bFF, FSH concentrations were maintained at normal intact levels for about 32 h following ovariectomy but then rose to normal ovariectomized levels. In ewes treated with 0.2 ml bFF, FSH concentrations increased immediately after ovariectomy but more slowly than in control ovariectomized ewes. Profiles of LH pulses were recorded after ovariectomy, during and after the withdrawal of bFF treatment. In ewes treated with the highest dose (1.8 ml s.c. every 8 h), mean LH levels and pulse amplitude were lower than in control ewes and increased significantly following withdrawal of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

The roles of inhibin and gonadotrophin-releasing hormone in the control of gonadotrophin secretion in the ewe.

The respective roles and relative importance of ovarian inhibition and hypothalamic stimulation in the differential control of the secretion of FSH and LH were studied in the ewe. In the first experiment two groups of ten intact ewes were injected i.v. twice daily with 9 ml charcoal-extracted bovine follicular fluid (bFF), a preparation rich in inhibin (3.65 ku./ml), throughout the luteal phase of the oestrous cycle. Compared with the control ewes, this treatment significantly reduced pituitary and plasma FSH concentrations and increased the frequency and amplitude of the LH pulses, but did not affect pituitary LH concentrations. In a second experiment, five control and five bFF-treated ewes from experiment 1 were ovariectomized and the injection regime was altered to 2.5 ml s.c. every 8 h. This treatment was maintained for 21 days. In control ewes, plasma FSH concentrations rose significantly within 12 h and continued to rise for 3-4 days. Treatment with bFF abolished this increase and maintained plasma FSH concentrations below those observed in intact ewes. The rise in mean plasma LH concentrations evoked by ovariectomy was also partially inhibited in the bFF-treated ewes. The response to the gonadotrophin-releasing hormone (GnRH) agonist buserelin (5 micrograms i.v.) was measured 6, 12 and 18 days after ovariectomy. In control ewes the agonist consistently evoked large surges of both hormones but in bFF-treated ewes the FSH response was completely blocked and the initial phase of the LH response (the first 'pool') was greatly reduced. In experiment 3, six ewes were ovariectomized and passively immunized against GnRH 3 days after oestrus. The increase in plasma LH which normally follows ovariectomy was completely abolished and mean concentrations remained very low and did not change over the following 14 days. In contrast, mean FSH concentrations rose significantly within 12 h of ovariectomy and continued to rise until the third day, after which they fell gradually. Treating three of the ewes with bFF (2.5 ml s.c. every 8 h) 8 days after ovariectomy and immunization further reduced the FSH concentrations. When the ewes were injected repeatedly (200 ng i.v., hourly for 5 h) with [D-penicillamine-(But)6]-GnRH(1-9)nonapeptide-ethylamide, a synthetic GnRH analogue which does not bind to the antiserum, there was a rapid rise in the secretion of LH in both control and bFF-treated animals but, as with the responses to buserelin, the initial response was significantly lower in bFF-treated than in control ewes.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

Effects of antidepressants and other psychotropic drugs on melatonin release and pineal gland function.

Antidepressants and some other psychotropic drugs affect the synthesis and release of melatonin through several mechanisms. Monoamine oxidase (MAO)-inhibiting antidepressants increase pineal concentrations of the melatonin precursors, serotonin (5-HT) and N-acetyl serotonin (NAS), in rodents, and also increase pineal N-acetyl transferase activity as well as both daytime and nighttime plasma melatonin concentrations; they also elevate melatonin, 5-HT and NAS in the cerebrospinal fluid of non-human primates. In humans treated with the MAO-A selective inhibitor, clorgyline, or the nonselective inhibitor, tranylcypromine, increased plasma melatonin also occurs; in contrast, the MAO-B selective inhibitor, 1-deprenyl, does not affect plasma melatonin. Chronically-administered tricyclic antidepressants with prominent effects on monoamine uptake and on beta-adrenoceptors reduce pineal and plasma melatonin in rodents; however, in two studies in depressed patients, either no change or a significant elevation in nocturnal plasma melatonin followed 3 to 4 weeks treatment with desipramine. As depressed patients in these and several other recent studies had lower pretreatment nighttime melatonin peaks than controls, these findings may be relevant to the presynaptic and receptor adaptational consequences of chronic antidepressant drug treatment. The significant effects on melatonin of other drugs which affect monoamine function and have psychotropic effects, including lithium, propranolol, amphetamine and several monoamine precursors, together with recent observations of the existence of muscarinic and benzodiazepine receptors in the pineal gland are in accord with previous suggestions that the study of pineal function and melatonin production provides a valuable model system for psychopharmacological investigations.

Animals↗
PubMed1979

The 8-isoprostaglandins: evidence for eight compounds in human semen.

Evidence is presented for the existence of a group of 8-iso prostaglandins in human semen, comprising 8-iso PG E1, 8-iso PG E2, 8-iso PG F1 alpha, 8-iso PG F2 alpha and the four corresponding 19-hydroxy prostaglandins. The E and F compounds have been positively identified by comparison of their mass spectra and chromatographic properties with those of authentic standards. Preliminary measurements of levels of these compounds in pooled semen are presented.

Chromatography, Thin Layer↗
PubMed1978

Daydreaming in the adolescent years: instrument development, factor analysis, and sex differences.

The Imaginal Processes Inventory (IPI), originally devised for college students, was revised for use with high school students. Nineteen of the original 28 IPI daydreaming scales were used and the response format was changed. The self-report instrument was completed by a racially diverse sample of 181 ninth through eleventh grade students. Reliable application of the Revised IPI to this population was demonstrated. Distinct sex differences, not previously reported, were found showing more acceptance of daydreaming for females and more guilt and fearfulness in daydreaming for males. Factor structures were similar to previous studies, but a generally higher level of daydreaming and less uncontrolled mind wandering was found for high school students than for college students. The research suggests that personality differences between men and women could be further explored by the daydreaming instrument and that sex differences must be taken into account in further research. Use of such daydreaming data is suggested in therapeutic intervention.

Adolescent↗
PubMed1976

Immunity to leptospirosis: renal changes in vaccinated cattle given challenge inoculum.

Resistance to renal leptospirosis was demonstrated in cattle vaccinated with Leptospira interrogans serotype pomona bacterin. Fewer vaccinated cattle given challenge inoculum of virulent serotype pomona leptospires 12 months after vaccination had kidneys with gross focal lesions in the cortex than did nonvaccinated controls. Histopathologic changes characteristically associated with renal leptospirosis occurred less frequently and renal tissue damage was less severe in vaccinated cattle than in nonvaccinated controls. The isolation of serotype pomona from only 1 of 29 vaccinated cattle, compared to 7 isolations from 11 nonvaccinated cattle, at 26 days after challenge inoculum was given, indicated that mild renal infection occurred only infrequently in vaccinated cattle. It appeared that challenge inoculation of vaccinated cattle with virulent serotype pomona leptospires stimulated an accelerated secondary immune response in which immunity limited the multiplication of leptospires in the kidney.

Animals↗