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Biomedical subjects

S Harvey

Publications and source records attributed to S Harvey.

At least 109 records · Page 6Linked to original sources
PubMed1993

Ultrastructural colocalization of growth hormone binding protein and pituitary hormones in adenohypophyseal cells of the rat.

GH receptor immunoreactivity is widely distributed within the rat pituitary gland, although apart from somatotrophs the cell types with GH receptor immunoreactivity have yet to be identified. It is also unknown whether this immunoreactivity reflects the presence of GH binding proteins (GHBPs) or authentic receptors. The possible colocalization of GHBPs and pituitary hormones in somatotrophs, lactotrophs, gonadotrophs, thyrotrophs, and corticotrophs was therefore examined using immunogold electron microscopy. Pituitary sections were indirectly immunostained with antibodies for GH, PRL, LH, FSH, TSH, or ACTH using gold-labeled immunoglobulin G. The same grids were also immunostained with a polyclonal antibody raised against rat GHBP using protein A conjugated to gold particles of a different size. Some sections were gold-labeled using a monoclonal antibody (MAb 4.3) raised against the unique hydrophobic tail of the GHBP, using gold-labeled immunoglobulin G. The cellular and ultrastructural distribution of immunoreactivity within the pituitary gland was similar after labeling with either GHBP antiserum. In all immunoreactive cells the labeling was most intense in secretory granules. Specific staining was not, however, demonstrated in the nucleus, in contrast with earlier findings using MAb 263. Moreover, while staining with MAb 263 appeared to be ubiquitous, some pituitary cells were not labeled by the polyclonal GHBP antiserum or by MAb 4.3. GHBP immunoreactivity was, however, colocalized with hormones in all pituitary cell-types, although in some cells GHBP immunoreactivity was not present in all secretory granules. These results clearly demonstrate the presence of GHBPs in adenohypophyseal cells, in which they appear to be stored or secreted with GH, PRL, LH, FSH, TSH, and ACTH. The function of GHBPs in the pituitary gland is, however, uncertain.

Adrenocorticotropic Hormone↗
PubMed1993

Growth hormone (GH) suppression of catecholamine turnover in the chicken hypothalamus: implications for GH autoregulation.

GH administered centrally or peripherally inhibits basal or secretagogue-induced GH secretion in domestic fowl. Since the release of pituitary GH is neurally regulated by the hypothalamus, GH autoregulation may be mediated by changes in the content or metabolism of hypothalamic monoamines. When chicken GH (500 micrograms/kg body weight) was injected i.v. into laying hens, tissue catecholamine (adrenaline, noradrenaline and dopamine) concentrations in the preoptic area (POA) and medial basal hypothalamus (MBH) were depleted for 2-24 h, as were concentrations of dihydroxyphenylacetic acid, a dopamine metabolite. The serotonin (5-HT) content of the POA and MBH was unaffected by i.v. GH administration, although a reduction in MBH 5-hydroxyindoleacetic acid suggested a tissue-specific inhibition of 5-HT turnover. Qualitatively similar results were observed in laying hens 24 h after the intracerebroventricular injection of chicken GH (10 micrograms/bird). These results therefore demonstrate aminergic actions of GH within the chicken hypothalamus which may mediate GH autoregulation. However, as amine metabolism is not only suppressed when endogenous GH secretion is reduced, but also at times when normal GH secretion is restored, these aminergic effects may also reflect other actions of GH on central function.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1993

Benzodiazepine antagonism of thyrotrophin-releasing hormone receptors: biphasic actions on growth hormone secretion in domestic fowl.

Benzodiazepines are pharmacological agents widely used for their anxiolytic and anticonvulsant properties. However, as these drugs are known to antagonize the binding and action of thyrotrophin-releasing hormone (TRH) in pituitary tissue, the possibility that they may modulate GH secretion was investigated in domestic fowl, in which TRH is a GH-releasing factor. Chlordiazepoxide (an antagonist of central-type benzodiazepine receptors) had no significant effect on the basal release of GH from incubated chicken pituitary glands, but at concentrations > 10 mumol/l chlordiazepoxide suppressed somatotroph responsiveness and sensitivity to TRH stimulation. At this concentration, chlordiazepoxide competitively displaced the binding of [3H]3-methyl-histidine2-TRH ([3H]MeTRH) to chicken pituitary membranes. The prior incubation of pituitary glands with chlordiazepoxide had no significant effect on the number of [3H]MeTRH-binding sites, which were also unaffected by the administration of chlordiazepoxide in vivo. However, contrary to its effects in vitro, chlordiazepoxide reduced basal GH secretion in vivo, whilst potentiating the GH response to systemic TRH challenge. These results demonstrate benzodiazepine antagonism of TRH-binding sites in domestic fowl and a biphasic modulation of GH secretion, which may be mediated through opposing actions at pituitary and central sites.

Animals↗
PubMed1993

Growth hormone receptor gene expression in sex-linked dwarf Leghorn chickens: evidence against a gene deletion.

GH receptor (GHR) mRNA has been identified in peripheral (liver and muscle) and central (brain and hypothalamus) tissues of sex-linked dwarf (SLD) Leghorn chickens. Total RNA was extracted from the tissues of immature (1 week, 4 week), pubertal (16 week) and adult (> 24 weeks) SLD and K (the normally growing strain) Leghorn chickens. In both groups and all tissues, an mRNA moiety of 4.4 kb hybridized with cRNA probes derived from the rabbit hepatic GHR sequence. An additional low-abundance transcript of 2.8 kb was also identified in some tissues. An age-related increase in expression was observed in K and SLD hepatic GHR mRNA, suggesting normal regulation of SLD GHR gene transcription. Amplification of cDNA from K and SLD tissues in the presence of oligonucleotide primers coding for the intracellular or extracellular domains of the chicken GHR generated electrophoretically separable fragments of expected size. Restriction enzyme digestion of the products with EcoRI, BstNI, HaeIII, NcoI or BamHI produced smaller moieties of expected sizes in both strains. These results demonstrate that, in contrast to broiler SLDs, a GHR gene deletion is not responsible for the GHR dysfunction in Leghorn SLDs. Although the actual defect in GHR gene expression in SLD Leghorns remains to be identified, this study demonstrates that sex-linked dwarfism, like Laron dwarfism, is due to a heterogeneity of lesions.

Animals↗
PubMed1993

pGlutamylglutamylprolineamide modulation of growth hormone secretion in domestic fowl: antagonism of thyrotrophin-releasing hormone action?

Pyroglutamyglutamylprolineamide (pGlu-Glu-ProNH2) is a tripeptide with structural and immunological similarities to thyrotrophin-releasing hormone (TRH; pGlu-His-ProNH2). Since TRH stimulates GH secretion in domestic fowl, the possibility that pGlu-Glu-ProNH2 may also provoke GH release was investigated. Unlike TRH, pGlu-Glu-ProNH2 alone had no effect on GH release from incubated chicken pituitary glands and did not down-regulate pituitary TRH receptors. However, pGlu-Glu-ProNH2 suppressed TRH-induced GH release from pituitary glands incubated in vitro and competitively displaced [3H]methyl3-histidine2-TRH from pituitary membranes. Systemic injections of pGlu-Glu-ProNH2 had no significant effect on basal GH concentrations in conscious birds, but promptly lowered circulating GH levels in sodium-pentobarbitone anaesthetized fowl. Submaximal GH responses of conscious and anaesthetized birds to systemic TRH challenge were, however, potentiated by prior or concomitant administration of pGlu-Glu-ProNH2. These results demonstrate, for the first time, that pGlu-Glu-ProNH2 has biological activity, with inhibitory and stimulatory actions within the avian hypothalamo-pituitary axis. These results indicate that pGlu-Glu-ProNH2 may act as a TRH receptor antagonist within this axis.

Animals↗
PubMed1993

Thyrotrophin-releasing hormone-induced growth hormone secretion in domestic fowl: concomitant stimulation of dopamine turnover in the medial basal hypothalamus.

Thyrotrophin-releasing hormone (TRH) stimulates GH secretion in domestic fowl by actions at pituitary and central nervous system sites. The possibility that this central action might be mediated by hypothalamic catecholamines or indoleamines was therefore investigated. When TRH was administered into the lateral ventricles of anaesthetized fowl the concentration of 3,4-dihydroxyphenylacetic acid (DOPAC, a metabolite of dopamine (DA)) in the medial basal hypothalamus (MBH) was increased within 20 min. The concentrations of MBH noradrenaline (NA), DA, serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were, however, unaffected by the intra-cerebroventricular (i.c.v.) administration of TRH, although the MBH concentrations of somatostatin and TRH were concomitantly reduced. A rapid increase in DA release into MBH extracellular fluid and its metabolism to DOPAC was also observed after i.c.v. or i.v. administration of TRH, in birds in which the MBH was perfused in vivo with Ringer's solution. Microdialysate concentrations of NA, 5-HT and 5-HIAA were not, however, affected by central or peripheral injections of TRH. Diminished GH responses to i.v. TRH challenge occurred in birds pretreated with reserpine (a catecholamine depletor), alpha-methyl-paratyrosine (a DA synthesis inhibitor) and pimozide (a DA receptor antagonist). These results therefore provide evidence for the involvement of a hypothalamic dopaminergic pathway in the induction of GH release following the central or peripheral administration of TRH. In contrast with its inhibitory actions at peripheral sites, DA would appear to have a central stimulatory role in regulating GH release in birds.

Amines↗
PubMed1992

The effects of continuous exposure to 20-kHz sawtooth magnetic fields on the litters of CD-1 mice.

Mated CD-1 mice were exposed to 20-kHz sawtooth magnetic fields similar to those associated with video display terminals (VDT). Four groups of animals were continuously exposed from day 1 to day 18 of pregnancy to field strengths of 0, 3.6, 17, or 200 microT. There were no less than 185 mated dams in each exposure group. On day 18, the dams were sacrificed and assessed for weight gain and pregnancy. The litters were evaluated for numbers of implantations, fetal deaths and resorptions, gross external, visceral and skeletal malformations, and fetal weights. There were no less than 140 pregnant females in each group, and there were no significant differences between any of the exposure groups and the sham group (0 microT) for any of the end points. The results of this study do not support the hypothesis that the 20-kHz VLF magnetic fields associated with video display terminals are teratogenic in mammals.

Abnormalities, Radiation-Induced↗
PubMed1992

Thyroid and adrenal function in the ring dove (Streptopelia risoria) during food deprivation and a breeding cycle.

The concentration of plasma triiodothyronine (T3), thyroxine (T4), corticosterone, and glucose as well as body weight and food intake were measured in pairs of ring doves throughout a breeding cycle and during food deprivation. During courtship and incubation the levels of plasma T4 were significantly higher in males than in females. A transitory decrease in food intake in both sexes was measured at the onset of incubation but was not associated with a change in body weight or in levels of plasma thyroid hormones. After the eggs had hatched, food intake increased but was associated with a reduction in body weight and concentrations of plasma T3 and T4, although plasma corticosterone and glucose both increased. Food deprivation for 48 hr resulted in a significant fall in the concentration of plasma T3 and an increase in plasma corticosterone. These changes suggest that all the food was not being digested by the adult birds during brooding but was almost exclusively regurgitated to feed the squabs.

Adrenal Glands↗
PubMed1992

Androgens are necessary for the establishment of secretory protein expression in the guinea pig seminal vesicle epithelium.

The guinea pig seminal vesicle epithelium (GPSVE) synthesizes and secretes milligram quantities of four related secretory proteins in an androgen-dependent manner. To investigate the role of androgens in the establishment of secretory protein synthesis during the development of the GPSVE, animals were castrated at Day 5, approximately 10 days before secretory protein accumulation begins in intact animals. Castration did not eliminate secretory protein mRNA from the SVE, but it did indefinitely postpone the developmentally programmed increase in secretory protein mRNA. Injection of neonatally castrated guinea pigs with either estradiol or dexamethasone did not alter levels of secretory protein mRNAs. However, treatment of castrated neonates with either testosterone propionate or dihydrotestosterone (DHT) led to specific increases in secretory protein mRNAs within 4 days. Although neonatally castrated animals accumulated and translated significant amounts of secretory protein mRNA, the newly synthesized secretory proteins failed to accumulate until exogenous androgens were provided. This observation suggests that androgens regulate both the accumulation of secretory protein mRNA and the accumulation of secretory proteins in the GPSVE.

Androgens↗
PubMed1992

Relationship between serum and saliva theophylline levels in patients with cystic fibrosis.

Theophylline levels in stimulated and unstimulated mixed saliva were compared with total and free (unbound) serum theophylline levels in 11 outpatients with cystic fibrosis (CF) who were using theophylline regularly. Stimulated saliva from CF patients predicted both total and unbound serum theophylline concentrations to within +/- 1 microgram/ml in 53.3 and 80.0%, respectively, of the samples examined. In addition, the total serum levels from CF patients could be used to predict unbound serum concentrations to within +/- 1 micrograms/ml in 100% of the cases examined. Furthermore, it was observed that prediction equations derived in a previous study with asthmatics employing identical methodology would allow both unbound and total serum theophylline levels to be predicted from saliva levels in CF patients with a degree of accuracy and precision that was approximately equal to or slightly better than the results obtained using prediction equations derived in other CF patients. These results indicate that saliva levels allow predictions of the unbound serum theophylline levels with greater accuracy and precision than they predict total serum theophylline levels. In addition, total serum levels can be used to reliably predict unbound serum levels. The use of mixed stimulated saliva is recommended as a reliable noninvasive method for monitoring unbound serum theophylline levels. The therapeutic range for saliva, which corresponds to the accepted total serum concentration range of 10-20 micrograms/ml, is approximately 5.55-11.3 micrograms/ml.

Adolescent↗
PubMed1992

Patterns of alcohol consumption in white collar-workers--a cross-sectional and longitudinal study.

A 6-year follow-up of a cohort of male and female white collar workers in whom there was baseline information on alcohol consumption and access to data on sickness absence, promotion and labour turnover, revealed that even moderate alcohol and consumption in this population was associated with social costs for the employer and the employee, particularly in terms of sickness absence. The longitudinal examination of consumption in this study suggests that early intervention in a drinking career may reduce alcohol consumption and consequently avoid years of morbidity and sickness absence, as well as having a favourable influence on promotion prospects and labour turnover.

Adult↗
PubMed1992

Variability of the serum protein binding of theophylline in patients with asthma and cystic fibrosis.

1. The serum protein binding of theophylline was studied in 28 asthmatics and 11 patients with cystic fibrosis (CF) who were receiving the drug regularly. Peak theophylline samples were collected at 2 week intervals on four occasions in each asthmatic and on three occasions in each CF patient. The binding was measured using ultrafiltration at 37 degrees C and pH 7.4. The total and free (unbound) theophylline concentrations were measured using high-performance liquid chromatography. 2. The mean free-fractions (+/- s.d.) in asthmatics (0.50 +/- 0.03) and in CF patients (0.51 +/- 0.04) were not significantly different. The intra- and inter-subject variability in the free-fraction (fu) was relatively small in both patient groups. The binding was found to be concentration-independent at serum theophylline concentrations up to 30.9 micrograms ml-1. The effects of age, gender, serum albumin and total serum protein on the free fraction were evaluated. 3. The results indicate that the binding of theophylline is similar in the two disease states. The low degree of variability in serum theophylline binding indicates that measurements of total serum theophylline concentrations will reflect unbound serum concentrations with acceptable accuracy in both patient groups studied.

Adolescent↗
PubMed1992

A six year longitudinal study of the occupational consequences of drinking over "safe limits" of alcohol.

Although much research has focused on the psychological, social, and economic consequences of heavy problem drinking, there has been far less attention paid to the consequences of "moderate" drinking. This study used a unique opportunity to carry out a six year follow up of a cohort of male and female white collar workers in whom there was baseline information on alcohol consumption and access to details on sickness absence, labour turnover, and promotion. It has provided evidence that even moderate alcohol consumption in the working population is associated with social costs for the employer and the employee, including substantial sickness absence, and lack of promotion in men, although the increase in labour turnover was not statistically significant. The longitudinal examination of consumption in this study suggests that early intervention in a drinking career may reduce alcohol consumption and consequently avoid years of morbidity and sickness absence, as well as having a favourable influence on performance and labour turnover.

Absenteeism↗
PubMed1992

Ubiquitous distribution of growth hormone receptors and/or binding proteins in adenohypophyseal tissue.

Liver GH receptor (GHR)-like mRNA has been shown to be widely distributed throughout rat and rabbit pituitary glands. In the present study RNA extracted from rabbit anterior pituitary glands was reverse transcribed, and the cDNA amplified by the polymerase chain reaction (PCR) in the presence of 3'- and 5'-flanking oligonucleotide primers for the extracellular and transmembrane domains of the rabbit GHR. A 499-basepair (bp) fragment was generated, identical in size to that in rabbit liver, kidney, and adipose tissue. Digestion of this fragment with a restriction endonuclease (SalI) produced moieties of 280 and 219 bp, as observed for the amplified cDNA fragments from liver, kidney, and adipose tissue. In situ hybridization of a cRNA probe for the rabbit GHR with cryostat sections of the anterior pituitary gland was demonstrated. Specific hybridization occurred throughout the adenohypophysis and was present in somatotroph and nonsomatotroph cells, identified by hybridization of the same tissue sections with a complementary riboprobe for rat GH mRNA. Electron microscopy and immunogold staining, using monoclonal antibodies against the extracellular domain of the rat (MAb 263) or rabbit (MAb 7) GHR, demonstrated the presence of the receptor or binding protein throughout rat and rabbit anterior pituitary gland. Immunostaining occurred in somatotroph and nonsomatotroph cells and was widely distributed throughout the intracellular and nuclear compartments. In GH-secreting cells gold particles were specifically accumulated in the secretory granules and heterochromatin, but were also present in mitochondria, Golgi, endoplasmic reticulum, cytoplasm, nucleoplasm, and cellular and nuclear membranes. A similar distribution of GHR immunoreactivity was observed within rat and rabbit hepatocytes. Specific binding sites for radiolabeled ovine GH to cytosolic fractions and to crude solubilized preparations of plasma and nuclear membranes of the rat anterior pituitary gland were also demonstrated. The binding of the tracer to these sites was inhibited by prior exposure to MAb 263, which binds to epitopes in the ligand-binding domain of the rat GHR. These results provide evidence of 1) the expression and translation of the GHR gene in rat and rabbit adenohypophysis in 2) GH and non-GH-secreting cells, and 3) the presence of GH receptors/binding proteins throughout the intracellular and nuclear compartments of these cells.

Animals↗
PubMed1992

Expression and translation of the growth hormone-receptor gene in the guinea-pig.

The refractoriness of guinea-pigs to the growth-promoting actions of exogenous GH has been suggested to be due to a deficiency or defect in tissue GH receptors or in GH-receptor gene expression. GH-receptor mRNA was, however, demonstrated by Northern blot analysis and by the polymerase chain reaction in extracts of guinea-pig liver, adipose tissue, brain, hypothalamus and pituitary gland. High-affinity, low-capacity binding sites for radio-labelled ovine GH were also demonstrated on the plasma membranes of guinea-pig liver and were similar to those in rat liver. These results demonstrate that the unresponsiveness of guinea-pigs to exogenous GH is not due to the absence of GH receptors.

Adipose Tissue↗
PubMed1992

Expression of the growth hormone receptor gene in chicken pituitary glands.

Although GH has no direct effect on GH release from chicken pituitary glands, GH receptor mRNA similar to that in the rabbit liver was identified by Northern blot analysis in extracts of adult chicken pituitaries. Complementary (c) DNA, reverse transcribed from chicken pituitary RNA, was amplified by the polymerase chain reaction (PCR) in the presence of 3'- and 5'-oligonucleotide primers coding for the extracellular domain of the chicken liver GH receptor and was found to contain an electrophoretically separable fragment of 500 bp, identical in size to that in chicken liver. Digestion of this pituitary cDNA with NcoI produced expected moities of 350 and 150 bp. Amplification of chicken pituitary cDNA in the presence of oligonucleotide primers for the intracellular sequence of the chicken liver GH receptor produced an electrophoretically separable fragment of approximately 800 bp, similar to that in chicken liver. This fragment was cut into expected moieties of 530 and 275 bp after digestion with EcoRI. These PCR fragments were identified in extracts of the pituitary caudal lobe, in which somatotrophs are confined and account for the majority of endocrine cell types, and in the cephalic lobe, in which somatotrophs are lacking. Translation of the GH receptor mRNA in the pituitary gland was indicated by the qualitative demonstration of radiolabelled GH-binding sites in plasma membrane preparations, in pituitary cytosol and in nuclear membranes. These results provide evidence for the expression and translation of the GH receptor gene in pituitary tissue, in which GH receptors appear to be widely distributed within cells and in different cell types. GH may therefore have paracrine, autocrine or intracrine effects on pituitary function.

Animals↗