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Biomedical subjects

D F Wood

Publications and source records attributed to D F Wood.

16 recordsLinked to original sources
PubMed1992

Preparation and characterization of an antibody specific to the rat dopamine D2 receptor.

Antibodies specific to the dopamine D2 receptor have been raised in rabbits using synthetic peptides. The resulting antiserum was sensitive to picogram quantities of peptide as measured by enzyme-linked immunoassay and was shown to have a 33% cross-reactivity with partially purified D2 receptor protein. No detectable cross-reactivity with similarly prepared fungal membranes was observed. D2 receptor preparations from normal rat pituitary cells were used in Western blot analysis. Bands of M(r) = 95,000 and 34,000 were detected in these preparations with a third faint band at 120,000. These correspond to the pituitary D2 receptor.

Animals↗
PubMed1991

Dopamine, the dopamine D2 receptor and pituitary tumours.

Dopamine plays an important role in the hypothalamic-pituitary axis where its major effects are to inhibit pituitary hormone secretion and cell division. Chronic dopamine deficiency has been postulated as a cause of pituitary tumour formation and several lines of evidence exist to suggest that a functional deficiency may develop as a result of defective dopamine receptor action. The available data suggest that a number of sites in the dopamine-D2 receptor-second messenger pathways may be implicated. These abnormalities are reflected in the variety of responses to dopamine and its agonists which have been observed in pituitary tumours both in the clinical situation and in cultured cells in vitro. Whilst it seems likely that the primary defect in pituitary tumour formation lies within the pituitary itself, the role of hypothalamic factors in facilitating tumour growth remains to be explored. Further studies of the dopamine receptor and its function will be of value not only in pathophysiological studies of human pituitary adenomas, but also in the development of new pharmacological agents to treat patients with these tumours.

Dopamine↗
PubMed1991

The dopamine D2 receptor is expressed in GH3 cells.

Some pituitary tumours respond to dopamine by decreasing the release of prolactin and/or GH and by inhibition of tumour growth. Certain tumours are unresponsive. Dopamine D2 receptor high-affinity binding is impaired in these tumours, and the rat GH3 cell line behaves in a similar way. The hypothesis that the dopamine-binding defect results from impaired D2 receptor gene expression has been tested in the present study. On Northern blots, D2 receptor mRNA was present in both normal rat pituitary cells and in GH3 cells. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis identified a putative D2 receptor protein in normal and GH3 cell membranes. The lack of effect of dopamine in GH3 cells does not reflect the absence of D2 receptor gene expression.

Animals↗
PubMed1990

Management of "brittle" diabetes with a preprogrammable implanted insulin pump delivering intraperitoneal insulin.

OBJECTIVE: Glycaemic control in a young woman with "brittle" diabetes. DESIGN: Use of a preprogrammable fully implanted pump (Infusaid) to deliver insulin intraperitoneally at variable rates, giving a total dose of about 60 units/24 h. SETTING: Endocrinology department in a teaching hospital. PATIENT: Thirty year old woman with 15 years' history of "brittle" diabetes. MAIN OUTCOME MEASURES: Glycated haemoglobin concentration; plasma glucose concentration. RESULTS: After implantation of the pump there was an immediate and sustained improvement in diabetic control. The patient's glycated haemoglobin concentration decreased from 15.2% to 9.2% over seven months. Her daily glucose concentrations were in the range 3.5-12 mmol/l. She has not been admitted to hospital since implantation of the pump, which was eight months before the time of writing. CONCLUSION: The implanted programmable intraperitoneal insulin pump may be of value in the management of patients with "brittle" diabetes in whom other attempts at glycaemic control have failed.

Adult↗
PubMed1989

Delayed puberty.

The pattern of physical development which occurs during normal puberty is described with reference to the underlying changes in hormone secretion. A summary of the causes of delayed puberty is given and the authors suggest a suitable protocol for investigation and management of this disorder.

Adolescent↗
PubMed1988

Effect of triiodothyronine treatment on thyrotrophin beta- and alpha-messenger RNAs in the pituitary of the euthyroid rat.

We have examined the effect of triiodothyronine (T3) treatment of the euthyroid rat on serum thyrotrophin (TSH) concentration, pituitary content of TSH and on pituitary cytoplasmic levels of TSH beta- and alpha-subunit messenger (m)RNAs, measured using the technique of dot hybridization to radiolabelled complementary (c)DNA probes. Serum concentration of TSH fell rapidly after T3 treatment of euthyroid rats, but no effect of T3 treatment was evident on pituitary TSH content. In contrast, marked effects of T3 on cytoplasmic levels of both TSH beta- and alpha-subunit mRNAs were demonstrated, with reductions in beta- and alpha-mRNAs at both early (6 h) and late (72 h) time points after administration of T3. These observations, which have not been documented previously in the euthyroid state, contrast with earlier findings in hypothyroidism in which stimulatory influences of T3 on TSH mRNAs are evident at 6 h.

Animals↗
PubMed1987

A comparison of the effects of bromocriptine and somatostatin on growth hormone gene expression in the rat anterior pituitary gland in vitro.

The effects of the dopamine agonist bromocriptine (BCR) have been compared with those of somatostatin (SS) on growth hormone (GH) synthesis and secretion by rat anterior pituitary cells in vitro. Both BCR and SS produced a dose-related reduction in GH release. Cytoplasmic GH mRNA levels were unchanged by BCR treatment and this finding was associated with an increase in total intracellular GH content. The reduction in GH release seen following SS treatment was accompanied by a fall in cytoplasmic GH mRNA levels and no significant change in intracellular GH content. These results suggest that the effects of BCR are predominantly on GH release mechanisms, whereas SS appears not only to regulate hormone release but also to regulate GH gene expression at a pre-translational level.

Animals↗
PubMed1987

Effect of hypothyroidism and thyroid hormone replacement in vivo on pituitary cytoplasmic concentrations of thyrotropin-beta and alpha-subunit messenger ribonucleic acids.

We have studied the influence of hypothyroidism and thyroid hormone replacement in vivo on rat pituitary cytoplasmic concentrations of TSH beta and alpha-subunit mRNA, measured by cytoplasmic dot hybridization, as well as circulating TSH and pituitary TSH content. Cytoplasmic concentrations of GH, PRL, and LH beta-subunit mRNA were measured in parallel. Marked increases in serum TSH and TSH beta and alpha mRNA were found in hypothyroidism; these changes reversed 72 h after beginning T3 replacement. A more marked effect of hypothyroidism on TSH beta mRNA than on alpha mRNA was evident, suggesting differential control of regulation of the TSH genes. In contrast to a rapid fall in serum TSH after T3 administration, an increase in TSH beta and alpha mRNA was evident at 1 and 6 h, followed by a later fall in TSH mRNA to euthyroid values. Pituitary cytoplasmic concentrations of GH and PRL mRNA were reduced in hypothyroidism and increased after administration of T3; LH beta mRNA was unaffected by hypothyroidism or T3 replacement. The differential effects of thyroid status on TSH, GH, PRL, and LH mRNA indicate specificity of regulation of these anterior pituitary hormone genes.

Animals↗
PubMed1987

The effect of thyroid hormones on growth hormone gene expression in vivo in rats.

Thyroid hormones are important regulators of GH synthesis and secretion. In this study we have made a detailed examination of the time-course of the effects of hypothyroidism and tri-iodothyronine (T3) replacement in the intact rat on GH gene expression in the anterior pituitary gland. Changes in pituitary cytoplasmic GH messenger (m)RNA levels were compared with total pituitary GH content and serum GH concentration during the development of hypothyroidism and following short-term T3 replacement in vivo. Hypothyroidism was associated with a fall in pituitary GH mRNA levels. Treatment of hypothyroid animals with T3 rapidly stimulated GH mRNA levels to values above those seen in euthyroid controls. The reduction in GH mRNA levels seen during the development of hypothyroidism was accompanied by a fall in serum GH and pituitary GH content, both of which were partially restored by T3 replacement. Thus thyroid hormone replacement in hypothyroidism rapidly stimulates GH mRNA synthesis, which is followed by the gradual restoration of pituitary GH stores and serum GH concentration.

Animals↗
PubMed1987

Modulation by oestrogen of thyroid hormone effects on thyrotrophin gene expression.

The role of oestrogen in the regulation of TSH gene expression is unclear. We have examined the effect of administration of oestrogen in the rat on serum TSH, pituitary TSH content and pituitary cytoplasmic concentrations of mRNA encoding the TSH beta and alpha subunits, thus deriving measures of hormone release and synthesis. In addition, we have examined the effect of oestrogen on the binding of tri-iodothyronine (T3) to nuclear receptors in the anterior pituitary. Administration of oestrogen did not affect serum concentrations of TSH in euthyroid or untreated hypothyroid rats, but did augment the effects of T3 (1 and 2 micrograms) on serum TSH in hypothyroid animals 6 h after injection of T3. No influence of oestrogen or of thyroid status on pituitary content of TSH was seen. A marked increase in the concentrations of TSH beta and alpha mRNA in pituitary cytoplasm was found in hypothyroidism, compared with those in the euthyroid state. No effect of oestrogen on TSH mRNA was seen in euthyroid animals but concentrations of TSH beta and alpha mRNA were lower in hypothyroid animals than in vehicle-treated controls. A stimulatory influence of T3 on TSH mRNA was seen 6 h after injection of T3; this stimulation was absent in oestrogen-treated rats. No effect of oestrogen on the action of T3 was evident 72 h after beginning treatment with T3. In addition to effects on serum TSH and TSH mRNA, an increase in the number of pituitary nuclear receptors for T3 was seen after oestrogen treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Thyroid status affects the regulation of prolactin mRNA accumulation by tri-iodothyronine and thyrotrophin-releasing hormone in cultured rat anterior pituitary cells.

The effects of tri-iodothyronine (T3) and TRH on prolactin mRNA accumulation in monolayer pituitary cell cultures prepared from both euthyroid and hypothyroid rats were investigated. Basal prolactin mRNA concentrations and prolactin release into culture medium were increased in hypothyroid cultures, the increase being related to the duration of hypothyroidism in vivo. The inhibitory effects of T3 seen in euthyroid cells were preserved in cells derived from hypothyroid animals, and the degree of inhibition was greater in cells from the most severely hypothyroid rats. However, the stimulation of prolactin synthesis and secretion induced by TRH in euthyroid cultures was not found in the hypothyroid cells. Hypothalamic and anterior pituitary TRH content were measured in similarly hypothyroid and euthyroid rats. A large hypothalamic pool of TRH was found, which was unchanged in hypothyroidism, whereas anterior pituitary TRH content was increased in the hypothyroid rats. The consequent down-regulation of anterior pituitary TRH receptors may explain the poor response of prolactin to TRH seen in vitro.

Animals↗
PubMed1987

Elevation of free thyroxine measurements in patients without thyrotoxicosis.

The recent development of single step analogue assay techniques to measure free thyroxine in serum has meant that this estimation has become widely used as a first line test of thyroid function. However these assays are subject to in-vitro interference in two ways: where there is a variant serum albumin in familial dysalbuminaemic hyperthyroxinaemia, or where there are circulating thyroid hormone binding antibodies. In both these situations a spuriously high result for free thyroxine is obtained. This may have serious implications for patient management and we describe 10 patients in whom the finding of a misleadingly high free thyroxine concentration led to confusion in diagnosis and, in eight of the 10, to inappropriate antithyroid treatment. Clinicians should be aware of these technical problems and where a result for the free thyroxine concentration seems inappropriate to the patient's clinical state then measurement of thyrotrophin (TSH) by a sensitive immunometric method should be performed. If the results remain confusing the presence of a variant serum albumin or thyroid hormone binding antibodies should be sought.

Adult↗
PubMed1987

Hormonal regulation of thyrotrophin synthesis and secretion.

We have examined the effects of triiodothyronine treatment on serum TSH and pituitary cytoplasmic TSH alpha and beta mRNA levels in the hypothyroid rat. Serum TSH and the cytoplasmic levels of the TSH alpha and beta subunit mRNAs rose concomitantly in hypothyroidism. Treatment of hypothyroid animals with triiodothyronine resulted in a fall in serum TSH but an initial increase in subunit mRNAs, followed by a reduction to euthyroid levels. We have also studied the modulation of these responses by oestrogen and testosterone administration. Treatment with oestradiol during the development of hypothyroidism gave rise to lower levels in alpha and beta subunit mRNAs compared with hypothyroid animals not receiving the oestrogen. Oestrogen also abolished the early rise in subunit mRNA levels seen following triiodothyronine replacement. Testosterone administration during the development of hypothyroidism had a similar effect to that of oestrogen in that subunit mRNA levels were lower in the androgen-treated hypothyroid animals than in hypothyroid animals receiving no exogenous androgen. These data suggest that gonadal steroids render the pituitary thyrotroph cell more sensitive to thyroid hormone.

Animals↗
PubMed1987

The use of a multiwire camera for the detection of 3H labelled cDNA/mRNA hybrids.

We have investigated the use of a multiwire camera for the rapid direct quantitation of 3H labelled cDNA/mRNA hybrids. Growth hormone (GH) complementary DNA (cDNA) probes were labelled with either 3H or 32P and used in dot-blot hybridization assays of pituitary cytoplasmic samples. The results were assessed either by counting in the multiwire camera (3H) or by autoradiography and scanning densitometry (32P). Results obtained by both methods were comparable over a similar range of pituitary cytoplasmic dilutions. The use of a multiwire camera may have several advantages over conventional methods for the detection of radioisotopically labelled cDNA/mRNA hybrids and has great potential for use in this field of endocrine research.

Animals↗