Biomedical subjects

S R Davis

Publications and source records attributed to S R Davis.

At least 109 records · Page 6Linked to original sources

PubMed1989

Human chorionic gonadotrophin-induced suppression of serum inhibin involves reduction in ovarian inhibin alpha-subunit messenger RNA levels in the pregnant mare serum gonadotrophin-primed female rat.

We have investigated the effect of administration of human chorionic gonadotrophin (hCG) to immature female rats pretreated with pregnant mare serum gonadotrophin (PMSG) on ovarian inhibin alpha-subunit mRNA, serum inhibin and circulating gonadotrophin levels. PMSG stimulation alone caused a 5-fold increase in relative inhibin alpha-subunit mRNA levels and a 12-fold increase in serum inhibin by 48 h. However, injection of hCG at 40 h suppressed PMSG-stimulated ovarian inhibin alpha-subunit mRNA and serum inhibin to levels at 48 h not statistically significantly different from controls. Serum follicle-stimulating hormone (FSH) fell after PMSG treatment, but rose after combined PMSG-hCG treatment. Serum luteinizing hormone (LH) was unchanged after PMSG alone but also rose after combined PMSG and hCG therapy. In conclusion, hCG suppresses ovarian inhibin synthesis in PMSG-stimulated immature female rats with preservation of the reciprocal relationship between inhibin and FSH. This immature female rat model therefore provides further insight into the effects of LH or hCG on granulosa cell inhibin production just prior to ovulation.

Animals↗

PubMed1989

Characterization of insulin-like growth factor binding proteins in ovine tissue fluids.

Competitive tracer binding studies using radioiodinated insulin-like growth factor-I and -II (125I-labelled IGF-I and 125I-labelled IGF-II) together with size exclusion chromatography and IGF-I affinity chromatography have been used to characterize IGF binding protein activity in ovine tissue fluids. Binding proteins of greater than 200, 150 and 40-50 kDa were revealed in these studies and shown to be widely distributed in body fluids. Thus, the greater than 200 kDa binding protein, which is IGF-II specific, is present in plasma from mature sheep, colostrum and follicular fluid as well as fetal sheep plasma. This may be the ovine equivalent of the soluble type-2 IGF receptor recently identified in rat serum. The presence of a 150 kDa binding protein, of mixed specificity for IGF-I and IGF-II, in fetal and mature sheep plasma was confirmed in these studies. This protein, previously believed to be restricted to vascular fluids, was also identified in mammary lymph, follicular fluid and as a minor component in vitreous humor. Binding proteins of 40-50 kDa were revealed in every fluid tested and multiple variants with distinct specificities were also suggested. This was investigated by IGF-I affinity chromatography using mature sheep plasma. Following passage through the affinity adsorbent, binding of 125I-labelled IGF-I to proteins in the 40-50 kDa region was abolished but when 125I-labelled IGF-II was used as tracer, a binding protein of 40-50 kDa was still observed. Thus sheep plasma contains at least two 40-50 kDa binding proteins. The competitive tracer binding studies indicated that one such protein demonstrates mixed specificity for IGF-I and -II while the other strongly favours IGF-II.

Animals↗

PubMed1989

Comparison of the effects of administration of recombinant bovine growth hormone or N-Met insulin-like growth factor-I to lactating goats.

Five goats were injected with GH (15 mg/day), three goats received systemic infusions of insulin-like growth factor (IGF)-I (43 nmol/h) and four goats received systemic infusions of physiological saline (20 ml/h) on days 4-6 of a 10-day experimental period during mid-lactation. Milk yield increased by an average of 24% in GH-treated goats by the time of the third injection. In contrast, milk yield of IGF-I-infused goats did not differ from saline-infused animals although two of three goats did show a small increase (12%) after 36 h of IGF-I infusion. With GH and IGF-I treatments plasma IGF-I concentrations increased similarly, reaching maxima of 100-130 nmol/l within 24 h. Plasma IGF-I concentration was relatively constant in saline-infused goats at about 50 nmol/l throughout the experiment. Total IGF-I bound to 50 kDa and 150 kDa binding proteins in plasma was increased by GH and IGF-I treatments but, in contrast to IGF-I, GH increased the proportion of IGF-I bound to 150 kDa binding protein. In a second experiment, four goats received systemic infusion of IGF-I (43 nmol/h) and four goats received systemic infusion of physiological saline (20 ml/h). There was no evidence that milk yield was changed during IGF-I infusion. However, when those goats which had previously received IGF-I infusions were injected with GH, milk yield increased by 30%.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Metabolic clearance of insulin-like growth factor-II in sheep.

The metabolic clearance of ovine insulin-like growth factor-II (IGF-II) was examined in sheep using 131I-labelled IGF-II. Following i.v. administration the tracer was distributed in a volume similar to that of the vascular space (58.5 +/- 3.3 ml/kg; mean +/- S.E.M., n = 5) and demonstrated a triphasic pattern of clearance. Size-exclusion chromatography of a plasma sample collected 1 min after injection revealed peaks of radioactivity corresponding to hormone complexed to binding proteins of 150 and 40-50 kDa (relative abundance 21 and 65% respectively), a high molecular weight binding protein (greater than 200 kDa; 5%) and 'free' tracer (9%). Chromatography of sequential plasma samples revealed different patterns of clearance for these constituents. Half-lives of 131I-labelled IGF-II complexed to the 150 and 40-50 kDa binding proteins, as calculated from rate constants for their decay, were 351 +/- 30 and 9.6 +/- 1.8 min respectively (n = 5). These differ markedly from estimates for the clearance of IGF-I (545 +/- 25 min, n = 8, and 34 +/- 2.3 min, n = 6) associated with carrier proteins of the same apparent molecular weights. This was reflected in calculated metabolic clearance rates for IGF-I (3.9 +/- 0.5 ml/min) and IGF-II (7.8 +/- 1.0 ml/min). Chromatography also revealed that free IGF-II was reduced to negligible levels by 12 min. In contrast, radioactivity eluting in the position expected for the greater than 200 kDa binding protein was cleared from the circulation very slowly.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Improved estimates of clearance of 131I-labelled insulin-like growth factor-I carrier protein complexes from blood plasma of sheep.

Clearance of protein-bound forms of insulin-like growth factor-I (IGF-I) from the circulation of sheep was determined using single injections of 131I-labelled ovine or [Thr59]-human IGF-I, in the 'free' form or prebound to 50 or 150 kDa plasma binding protein fractions. The half-life of circulating protein-bound forms of IGF-I was determined by size-exclusion chromatography of plasma samples taken over a 24- to 26-h experimental period. IGF-I bound to lower molecular weight binding protein(s) (approximately 50 kDa) showed a half-life of 26-40 min (mean 34 min; n = 6), while the half-life of a high molecular weight fraction (150 kDa) was considerably longer (range 398-603 min; mean 545 min; n = 8). Metabolic clearance of IGF-I following administration of free tracer ranged from 3.0 to 5.3 ml/min in sheep (n = 4) weighing 26.0-28.5 kg. Tracer distribution volume was 59 ml/kg liveweight (n = 4). Tracer degradation products were first detected in plasma 8 h after i.v. administration. No differences in stability of the purified ovine and recombinant human IGF-I tracer preparations were observed. However, a fraction of the [Thr59]-IGF-I tracer did not possess binding activity and this was associated with excretion of a greater proportion of administered radioactivity (over 22 h) in urine in animals receiving [Thr59]-IGF-I tracer (18.4-19.3%) compared with ovine IGF-I (7.1-11.0%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

Pregnant mare's serum gonadotropin stimulates inhibin subunit gene expression in the immature rat ovary: dose response characteristics and relationships to serum gonadotropins, inhibin, and ovarian steroid content.

We have investigated the temporal changes and dose responses of ovarian inhibin gene expression, circulating inhibin, and ovarian estradiol content in PMSG-primed immature female rats. The relative levels of ovarian inhibin alpha- and beta A-subunit messenger RNA (mRNA), serum inhibin, and ovarian steroid content were measured after stimulation of immature female rats with 20 IU PMSG. Each of these variables rose in parallel and peaked at 48 h (relative ovarian inhibin alpha- and beta A-subunit mRNA increased 3.8-fold and 2.8-fold, respectively, serum inhibin 269 U/ml, vs. control 31, P less than 0.01, ovarian estradiol content 114 pmol/pair of ovaries vs. controls 4.7 P less than 0.001), corresponding to the time of maximal follicular development in this animal model. Subsequently each fell to reach a nadir at 96 h. The data are consistent with the hypothesis that PMSG stimulation of inhibin secretion occurs by a mechanism involving inhibin gene transcription. The increase in ovarian inhibin and estradiol synthesis during folliculogenesis and their simultaneous decline before ovulation suggest that 1) the circulating levels of inhibin and estradiol reflect follicular maturation and 2) these two hormones are regulated via a common mechanism during follicular development in the rat.

Animals↗

PubMed1988

Effects of thyroxine and growth hormone treatment of dairy cows on milk yield, cardiac output and mammary blood flow.

Four cows received thyroxine injections (T4; 20 mg/d) and three cows received growth hormone injections (GH; 44 mg/d) for 4 d during successive 16-d experimental periods. Measurement was made of milk yield, protein yield, mammary tyrosine and phenylalanine uptake, blood plasma hormone concentrations, mammary blood flow and cardiac output. Milk yield increased by 25% with T4 and 21% with GH treatment. Milk protein content tended to decline during T4 treatment and increase following GH treatment. Cardiac output increased by 8.9 liter/min (20%) and 4.6 liter/min (10%) with T4 and GH injection. Mammary blood flow (half-udder) increased from 3.6 to 4.9 liter/min (35%) and from 3.3 to 4.4 liter/min (33%) with T4 and GH treatment, respectively. These increases calculated on a whole-udder basis, accounted for 28% (T4) and 48% (GH) of the increases in cardiac output. The proportion of cardiac output perfusing the (whole) udder increased to 19.1% (T4) and 18.7% (GH), increases of 17 and 30%, respectively. Heart rate increased with T4 (but not GH treatment) from 80 to 115/min. Ratio of blood flow to milk yield was not changed by either treatment. The proportion of cardiac output perfusing the udder likely plays a major role in facilitating the partitioning of nutrients for milk synthesis.

Animals↗

PubMed1988

Effects of thyroxine and growth hormone treatment of dairy cows on mammary uptake of glucose, oxygen and other milk fat precursors.

Four cows received thyroxine injections (T4; 20 mg/d) and three cows received growth hormone injections (GH, 44 mg/d) for 4 d during successive 16-d experimental periods. Milk fat, lactose output, mammary uptake of glucose, oxygen and milk fat precursors were determined with each treatment. Injection of T4 increased lactose yield by 25% and fat yield 42%. The injection of GH increased fat and lactose yields by 24%. Both GH and T4 increased mammary glucose uptake by 35% and 45%, respectively, while T4 administration was associated with an increase in plasma glucose concentration from 67 to 84%. Thyroxine, but not GH, increased the ratio of mammary glucose uptake to lactose output from 1.24 to 1.58. Blood plasma acetate concentration declined following GH and T4 treatment by 17%. Mammary acetate uptake increased in response to GH injection in two of three cows but did not change with T4 injection. The injection of GH had no effect on plasma propionate concentration or mammary uptake. Thyroxine reduced plasma propionate content and mammary uptake. Neither T4 nor GH changed plasma free fatty acid concentration or mammary uptake. Thyroxine had no effect on plasma triglyceride concentration or mammary uptake, whereas GH increased mammary triglyceride uptake to the end of the experimental period. Mammary oxygen uptake was increased by GH as milk production increased. Increased mammary oxygen uptake following T4 treatment was transient. Change in mammary metabolism with T4 treatment permitted increased milk output without change in mammary oxygen consumption. Such a change may involve increased mammary utilization of pre-formed long-chain fatty acid and increased metabolism of glucose via glycolysis.

Animals↗

PubMed1988

The effect of hypophysectomy on inhibin production by adult rat ovaries: changes in ovarian inhibin gene expression and serum inhibin.

We have investigated the effect of hypophysectomy on adult rat ovarian inhibin alpha- and beta A-subunit mRNA, serum inhibin, and circulating gonadotrophin levels. Immediate declines in ovarian inhibin gene expression and serum inhibin were observed following hypophysectomy, with a nadir on day 4. However, inhibin synthesis determined by these parameters was still apparent at 16 days post-hypophysectomy. Gonadotropin levels were suppressed following hypophysectomy and the fall in inhibin production was highly correlated with disappearance of FSH from the circulation. This study demonstrates that removal of pituitary gonadotropin stimulation results in diminished ovarian inhibin synthesis and provides further evidence indicating that FSH stimulates granulosa cell inhibin synthesis by enhancing inhibin gene transcription.

Animals↗

PubMed1987

Effect of nutrition and immunization against somatostatin on growth and insulin-like growth factors in sheep.

The effect of immunizing against somatostatin (SRIF), with SRIF conjugated to bovine thyroglobulin, was examined in cross-bred sheep fed either cut pasture or lucerne pellets. Plasma concentrations of GH were unaffected by SRIF immunization, but were lower in pellet-fed sheep. Plasma concentrations of insulin-like growth factor I (IGF-I) increased after immunization in sheep on both diets. Pasture-fed sheep had lower plasma concentrations of IGF-I than those on pellets. Sheep showed a small increase in growth rate in response to immunization. Immunization had no effect on carcass composition and did not affect plasma concentrations of IGF-II, free fatty acids or glucose. The results show that even though SRIF immunization increases plasma concentrations of IGF-I, it does not necessarily result in a large increase in growth rate.

Animal Nutritional Physiological Phenomena↗

PubMed1987

Effects of injecting growth hormone or thyroxine on milk production and blood plasma concentrations of insulin-like growth factors I and II in dairy cows.

Three cows received injections of thyroxine (T4; 20 mg/day), four cows GH (40 mg/day) and three cows saline (control; 10 ml/day) on days 5-8 of a 16-day experimental period during peak lactation. Milk yield increased 13% in cows given GH (from 14.6 to 16.5 kg/day) and 15% in cows given T4 (from 15.8 to 18.2 kg/day) but did not change in control cows. Injection of T4 increased milkfat and lactose content but reduced milk protein content. Injection of GH was without effect on milk composition during the injection period but milk protein rose after injections ceased. Injection of T4 increased plasma concentrations of T4 and tri-iodothyronine six- to sevenfold, with maxima occurring on day 9. Injection of GH increased the plasma concentration of GH five- to tenfold 5 h after injection. The plasma concentration of insulin-like growth factor I (IGF-I) was increased in cows given GH in both morning (08.30 h) and afternoon (14.30 h) blood samples, the difference being greatest in afternoon samples in which plasma IGF-I content increased from 3.3 to 6.8 nmol/l. Injection of T4 reduced the plasma concentration of IGF-I in morning samples but the concentration in afternoon samples remained relatively constant throughout the 16-day experimental period. The plasma concentration of IGF-II rose in morning samples in all treatment groups to reach a maximum of 200-250 nmol/l by day 9. The galactopoietic response to injection of GH but not T4 was associated with an increase in plasma concentration of IGF-I. Changes in plasma concentration of IGF-II were not associated with changes in milk yield.

Animals↗

PubMed1987

Metabolic clearance rate of insulin-like growth factor-I in fed and starved sheep.

The metabolic clearance of insulin-like growth factor-I (IGF-I) has been examined in sheep using a radioiodinated hormone preparation (131I-labelled IGF-I). Following i.v. administration, 131I-labelled IGF-I was distributed in a volume equivalent to plasma (60 ml whole blood/kg liveweight) and demonstrated a triphasic pattern of clearance with apparent half-lives (t 1/2) of 4.0 +/- 0.4 (S.E.M.), 52.4 +/- 3.4 and 792 +/- 26.5 min (n = 10). No significant differences in the t1/2 of the three phases were identified in fed compared with starved animals (fed, n = 4, phase 1 = 3.1 +/- 0.64, phase 2 = 46 +/- 5.9 and phase 3 = 756 +/- 27 min; starved, n = 6, phase 1 = 4.6 +/- 0.58, phase 2 = 57 +/- 3.2 and phase 3 = 816 +/- 38.5 min). Similarly, no significant differences in the distribution volume (fed, n = 4, 44 +/- 4 ml/kg live-weight; starved, n = 6, 39 +/- 2 ml/kg liveweight) or metabolic clearance rate (fed, n = 4, 2.9 +/- 0.15 ml/min; starved, n = 6, 3.2 +/- 0.5 ml/min) of the IGF-I were found in fed compared with starved animals. High-performance gel filtration chromatography of sequential plasma samples following injection of 131I-labelled IGF-I revealed three clear peaks of radioactivity which demonstrated markedly different patterns of clearance. These correspond to hormone complexed to binding proteins of 150,000 and 50,000 daltons and to 'free' hormone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Inhibin gene expression in the human corpus luteum.

We report inhibin alpha- and beta A-subunit gene expression in the human corpus luteum and placenta using human alpha-subunit and bovine beta A-subunit nucleic acid probes. In addition, we have demonstrated the presence of immunoreactive and bioactive inhibin in human corpora lutea. Our findings suggest that this tissue is a significant source of inhibin during the luteal phase of the normal human menstrual cycle.

Corpus Luteum↗

PubMed1987

Physiology of the somatotropic axis with particular reference to the ruminant.

The physiology of growth hormone and the insulin-like growth factors are reviewed with particular reference to the dairy industry. Growth hormone secretion in the ruminant is pulsatile in nature and nutritional factors have a major impact on its secretion. Isolation of growth hormone-releasing factor has allowed further progress in understanding the mechanisms underlying growth hormone release. The receptors appear to be under active endocrine and metabolic control, and nutritional influences on the somatotropic axis are in large part mediated through changes in somatotropic receptors. The mode of action of growth hormone to induce acute metabolic affects and lipolysis remains to be resolved, but there is increasing evidence that its anabolic actions are mediated by the insulin-like growth factors. Recent studies of measurement of insulin-like growth factor-1 and -2 in the ruminant and the role of growth hormone, nutrition, insulin, and sex steroids in their regulation are reviewed. The relative role of the two factors and the multiple forms of their receptors remain to be resolved. It is well-documented that growth hormone is galactopoietic. The evidence that this effect is largely due to enhanced nutrient supply to the mammary gland is not convincing. Effects of growth hormone are indirect and may be mediated by the insulin-like growth factors. The potential is considerable for manipulating the growth hormone insulin-like growth factor axis to enhance lactation.

Animals↗

PubMed1986

Inhibin A-subunit gene expression in the ovaries of immature female rats is stimulated by pregnant mare serum gonadotrophin.

We have used a bovine cDNA probe for the A-subunit of inhibin to demonstrate the presence of inhibin in the ovaries of immature female rats: the levels of mRNA were increased following treatment of the rats with pregnant mare serum gonadotrophin (PMSG), suggesting modulation by PMSG of ovarian inhibin synthesis at least at the level of transcription. Furthermore, we report the unexpected finding of significant levels of inhibin mRNA in the corpora lutea of mature female rats. No inhibin mRNA was demonstrable in the uterus or placenta.

Age Factors↗

PubMed1986

Fluoxymesterone stimulation of tumor marker secretion in patients with breast carcinoma.

The gross cystic disease fluid protein of 15,000 MW (GCDFP-15) has been demonstrated to be a circulating glycoprotein tumor marker for breast carcinoma in approximately 40% of patients with advanced disease. A recent retrospective analysis of plasma GCDFP-15 levels in patients with advanced breast cancer suggested that androgen therapy could cause significant increases in plasma levels in the absence of disease progression. In order to evaluate the frequency, time course, and intensity of the androgen effect on GCDFP-15 production, a prospective study was initiated. Twenty-nine patients with stage IV breast carcinoma were treated with fluoxymesterone (20 or 30 mg/d). Plasma levels of GCDFP-15 and carcinoembryonic antigen (CEA) were measured by radioimmunoassay before and at various times during therapy. By day 6 of therapy, plasma GCDFP-15 had increased significantly (p = 0.03) from a mean basal level of 58 +/- 12 ng/ml to 160 +/- 60 ng/ml. By contrast, the mean CEA levels in the same patients increased only from 36 +/- 14 ng/ml. The distribution of percent increases in plasma GCDFP-15 was not uniform, but patients with high (greater than 82 ng/ml) basal levels had marked (greater than or equal to 75%) increases in 6/6 (100%) cases, whereas patients with low (less than 30 ng/ml) basal levels had similar increases in only 2/15 (13%) cases. Urinary excretion of GCDFP-15 usually paralleled the increases in plasma levels of the glycoprotein during the first six days of therapy. A linear correlation between percent change in plasma and percent change in urinary GCDFP-15 was demonstrated. A permanent cell line of human breast carcinoma, T47-D, was stimulated to secrete GCDFP-15 in vitro by androgen, but not by estrogen. From these data, we conclude that androgens can specifically stimulate secretion of GCDFP-15 by breast carcinoma tissue in most patients with elevated plasma levels of GCDFP-15, and in some patients with normal levels. The stimulation occurs within days and is not associated with clinical signs of tumor growth.

Apolipoproteins↗

PubMed1986

Estimation of tissue protein synthesis in sheep during sustained elevation of plasma leucine concentration by intravenous infusion.

1. The fractional rate of protein synthesis (FSR) was determined in skeletal muscle, liver, rumen and cardiac muscle of wether sheep by continuous intravenous infusion of L-[4,5-3H]leucine accompanied by infusion of 0, 7.6, 15.2 or 22.8 mmol leucine/h (three sheep per treatment). FSR was calculated assuming plasma (ksp) or intracellular (ksi) leucine-specific radioactivity (SRA) was representative of the leucine precursor pool SRA for protein synthesis. 2. Plasma leucine concentration (plateau) was linearly related to leucine infusion rate, 22.8 mmol/h evoking a tenfold increase in plasma concentration. 3. Difference between plasma leucine SRA and intracellular leucine SRA in all tissues diminished as plasma leucine concentration increased. 4. There were significant differences between ksi and ksp estimates for liver and rumen in control sheep. 5. As leucine infusion rate increased, differences between ksi and ksp diminished in all tissues. With increasing leucine infusion, in liver ksi decreased and ksp was increased, in rumen ksi decreased and ksp was stable, while in cardiac and skeletal muscle ksi and ksp both increased. 6. At a leucine infusion rate of 22.8 mmol/h, mean ksp and ksi respectively were: 11 (SE 2), 13 (SE 1); liver 19 (SE 2), 21 (SE 2); cardiac muscle 3.6 (SE 0.4), 3.8 (SE 0.3); skeletal muscle 4.1 (SE 0.2), 4.5 (SE 0.5) and did not differ significantly in any tissue.

Animals↗

PubMed1985

Measurement of DNA-protein crosslinks in mammalian cells without X-irradiation.

To study the mechanisms of formation and repair of DNA-protein crosslinks in mammalian cells, the best general method to assay these lesions is the Kohn membrane alkaline elution procedure. Use of this sensitive technique requires the introduction of random strand breaks in the DNA by X-irradiation to reduce the very high molecular weight so that it elutes off the filter at an appropriate rate. This report describes an alternative method for fragmenting the DNA in the absence of X-irradiation equipment. Convenient reproducible elution rates of DNA from various mouse and human cells in culture without X-irradiation result from elution through polyvinyl chloride filters with 75 mM sodium hydroxide (0.33 ml/min) instead of the standard 20 mM EDTA-tetrapropylammonium hydroxide, pH 12.2 (0.03 to 0.04 ml/min). Dose-dependent retardation of the DNA elution was observed over the range 0 to 30 microM trans-platinum(II)diamminedichloride, and proteinase K treatment during cell lysis restored the elution rate to that of the untreated control cell DNA. In the absence of X-irradiation, this elution method measures DNA-protein crosslinks with higher sensitivity and equivalent reproducibility as the air-burst procedure.

Animals↗