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Search for other papers by L.A. SALAKO in
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Search for other papers by A. J. SMITH in
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SUMMARY
Extracts of porcine thyroid containing calcitonin produced increases in urinary flow and urinary electrolyte content when infused or injected into anaesthetized rabbits. This response occurred more rapidly after intraaortic than after intravenous injection and was accompanied by an increase in glomerular filtration rate (inulin clearance) and renal plasma flow (paraaminohippuric acid clearance).
Preparations of calcitonin failed to affect the short-circuit current in isolated frog skin.
Although an effect of calcitonin on renal tubular transport mechanisms cannot be excluded it seems likely that one mechanism responsible for the diuretic effect of this compound in the rabbit is an increase in renal blood flow.
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SUMMARY
The qualitative and quantitative metabolism of testosterone in vitro by normal and neoplastic breast tissues of BR6 mice has been investigated. These tissues contain a Δ4-5α steroid reductase, 3-oxosteroid reductase and 17β-hydroxysteroid oxidoreductase. Qualitatively, the pregnancy-dependent and independent tumours differ in that the latter produce androst-4-ene-3α,17β-diol (androstenediol) whereas the former do not. This metabolite could not be detected in incubations with normal mammary tissue from pregnant mice. In general, tumours were more active than normal tissue from pregnant animals. No conversion of testosterone to oestrone or oestradiol was detected.
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ABSTRACT
The effect of administration of bovine somatotrophin (bST) on peripheral conversion of thyroxine (T4) to tri-iodothyronine (T3) was studied in non-pregnant lactating Holstein cows. Six cows were injected daily for 5 days with 40 mg recombinantly derived bST, while six control cows received excipient alone. Blood samples were collected hourly from 08.00 to 19.00 h on a single day the week before treatment and on days 4–5 of treatment. All other tissue samples were obtained at slaughter, 20–23 h after the last injection.
Administration of bST increased milk production and caused a 9% increase in hepatic DNA. Consumption of feed did not differ between control and bST-treated cows. Treatment did not alter serum concentrations of T4 or T3, although concentrations of thyroid hormones in the serum increased from 08.00 to 19.00 h. Activity of thyroxine-5′-monodeiodinase (5′-D) in liver and kidney was similarly unaffected. However, activity of 5′-D in mammary tissue increased approximately twofold in response to bST administration. We suggest that an increase in mammary conversion of T4 to the more biologically potent thyroid hormone T3 plays a role in mediating the galactopoietic response of dairy cattle to bST.
Journal of Endocrinology (1989) 121, 205–211
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Search for other papers by J. A. SMITH in
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Experiments on the metabolism of [4-14C]testosterone by the mammary gland of pregnant rats and by mammary tumours induced with dimethylbenzanthracene indicated the formation of a minor metabolite with the same chromatographic behaviour as testosterone acetate. A similar compound was found in the mammary gland of pregnant mice and in spontaneous mammary tumours in mice. This note describes the identification of this new metabolite of testosterone.
[4-14C]Testosterone (3 μc, specific activity 21·7 μc/μmole) was incubated with mammary tissue slices, weighing 0·5 g., in 2·5 ml. Krebs-Ringer phosphate solution of pH 7·4 for 2 hr. at 37°. The extraction procedure and Girard separation have been described elsewhere (King, Gordon & Helfenstein, 1964). The ketonic fraction was applied to an alumina column (Kellie & Wade, 1957) as modified by King et al. (1964). The radioactive material eluted with 20–45 ml. of 0·15% ethanol in benzene contained mostly androstanedione and androstenedione
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Search for other papers by G. K. SMITH in
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* Department of Physiology & Biochemistry, The University, Whiteknights, Reading, RG6 2AJ, and † Imperial Chemical Industries Ltd, Pharmaceuticals Division, Mereside, Alderley Park, Macclesfield, Cheshire, SK104TG
(Received 4 April 1975)
Fraps (1961) proposed that in the hen an 'excitation' hormone secreted by the developing follicle initiated the release of the luteinizing hormone (LH) required for ovulation. Since progesterone induced premature ovulation in the hen (Fraps & Dury, 1943) it was considered the most likely candidate for such a role. Evidence showing that plasma progesterone rises either immediately before, or coincidentally with, the plasma LH surge is consistent with this hypothesis (Furr, Bonney, England & Cunningham, 1973). It has been demonstrated recently, however, that oestradiol (Senior & Cunningham, 1974) and testosterone (Etches, 1974) are also increased before the preovulatory rise in LH, which means that they cannot be precluded from consideration. Certainly there is ample evidence that oestradiol induces the LH
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Search for other papers by T R Smith in
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Abstract
Preincubation of rat soleus muscle with 1 and 10 μm monensin for 2 h increased the subsequent basal 2-deoxyglucose uptake by muscle 76 and 121% respectively. Under the same conditions, monensin decreased the insulin-stimulated (1 mU/ml) 2-deoxyglucose uptake by 29 and 37% respectively. The monensin-induced augmentation of basal 2-deoxyglucose uptake was inhibited 92% by cytochalasin B suggesting that the uptake is mediated by glucose transporters. Monensin did not increase the cellular accumulation of l-glucose in muscle indicating that it does not affect the cell membrane integrity. Neither the stimulatory effect of monensin on basal 2-deoxyglucose uptake nor the opposite, inhibitory action of monensin on the insulin-stimulated 2-deoxyglucose uptake were influenced by the removal of Ca2+ from the medium or by dantrolene, an inhibitor of Ca2+ release from the sarcoplasmic reticulum, suggesting that the actions of monensin are not mediated by calcium. Monensin had no effect on muscle ATP concentration. The monensin-induced augmentation of basal 2-deoxyglucose uptake was neither associated with stimulation of muscle phosphatidylinositol 3-kinase activity nor inhibited by wortmannin, demonstrating that the increase in basal 2-deoxyglucose uptake is not mediated by activation of phosphatidylinositol 3-kinase. The inhibition of insulin-stimulated 2-deoxyglucose uptake by monensin was associated with a 31% decrease in the abundance of insulin receptors in muscles, a 64% decrease in the insulin-induced autophosphorylation of the insulin receptor β-subunit, and a 44% reduction of the insulin-stimulated phosphatidylinositol 3-kinase activity. Addition of monensin into the phosphatidylinositol 3-kinase reaction had no effect on the activity of the enzyme, demonstrating that the inhibition in monensin-treated muscles is indirect and occurs upstream of phosphatidylinositol 3-kinase. It is concluded that monensin has a dual effect on 2-deoxyglucose uptake by skeletal muscle: it stimulates basal uptake but inhibits the insulin-stimulated uptake. The primary cause of the latter, inhibitory effect of monensin is at the level of the insulin receptor.
Journal of Endocrinology (1997) 154, 85–93
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The presence of calcium in the fluid in which intestinal or kidney tissue is incubated is required for the tissue to respond to angiotensin. Everted sacs of rat colonic mucosa exhibited an increased rate of fluid transport in the presence of angiotensin; this response was lost when the serosal fluid, but not the mucosal fluid, was calcium-free. Angiotensin-stimulated transport was maintained when calcium was replaced with strontium or barium, but was lost when calcium was exchanged for magnesium. Similarly, calcium ions were required in the incubation fluid of rat kidney cortex slices to demonstrate angiotensin-enhanced sodium transport. These observations are discussed in relation to the possible roles of divalent cations in the mechanism of action of angiotensin.
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Search for other papers by A. I. Smith in
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ABSTRACT
Acid extracts of bovine preovulatory granulosa cells and corpora lutea (CL) were subjected to high-performance liquid chromatography (HPLC) and found to contain two peaks of immunoreactive (ir) oxytocin (OT), one corresponding to authentic OT and the second eluting 8 min later. The second peak was more abundant than authentic irOT in preovulatory follicles and in the early CL, but became less abundant as the CL matured (mid luteal) and was close to the limit of detection in the late CL. This peak could be detected only by an OT antiserum which recognized both the biologically active form of OT, as well as the post-translational processing intermediate Gly10-extended oxytocin. A second more specific OT antiserum (OT-933) did not recognize the second peak as strongly. Further analysis of the second peak revealed a complex of OT bound to its neurophysin (NP-I) which could be dissociated under denaturing conditions. Furthermore, we were able to create this complex in vitro by combining the two materials together under acid conditions, similar to the pH predicted in secretory granules, but not under neutral conditions. Measuring irNP-I by radioimmunoassay showed a single peak with a similar retention time to the OT/NP-I complex, confirming the identity of the unknown peak. Incubation of CL slices in culture showed a time-related release of both OT and NP-I, with OT having a greater rate of release in the mid luteal CL.
These data suggest the presence of an OT/NP-I complex in the bovine preovulatory granulosa cells and CL, as well as the unbound peptide presumably within the secretory granules. The ratio of OT/NP-I complex and free peptide changes with ageing of the the CL, perhaps indicating regulated differences in the post-translational processing of the prohormone.
Journal of Endocrinology (1991) 128, 305–314
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Search for other papers by CAROLINE MACNAUGHTAN in
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Search for other papers by MARGERY A. SMITH in
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Search for other papers by BARBARA SMYTH in
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SUMMARY
Higher temperatures allow lower sulphuric acid concentrations and shorter heating times to be used in the Kober colour reaction for oestrogens. A one-stage reaction which is completed in 5 min. at 120° is described for oestrone and oestradiol, and a two-stage reaction which requires two periods of heating for 5 min. at 120° is described for oestriol. The conditions were applied to the Ittrich fluorescence procedure. A spectrophotofluorimetric correction was developed in which fluorescence was measured at wavelengths for excitation and emitted light near the optima for the oestrogens and at another combination at which the oestrogens produced virtually no fluorescence whereas that of impurities was not diminished. Extraction, centrifugation and fluorimetry were performed in specially designed cells. The sensitivity is 0·05–0·1 ng./sample with a linear response up to 300 ng. and a precision better than 4% in the range 1·0–100 ng.
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Pituitary tumor-transforming gene (PTTG)-binding factor (PBF; PTTG1IP) was initially identified through its interaction with the human securin, PTTG. Like PTTG, PBF is upregulated in multiple endocrine tumours including thyroid cancer. PBF is believed to induce the translocation of PTTG into the cell nucleus where it can drive tumourigenesis via a number of different mechanisms. However, an independent transforming ability has been demonstrated both in vitro and in vivo, suggesting that PBF is itself a proto-oncogene. Studied in only a limited number of publications to date, PBF is emerging as a protein with a growing repertoire of roles. Recent data suggest that PBF possesses a complex multifunctionality in an increasing number of tumour settings. For example, PBF is upregulated by oestrogen and mediates oestrogen-stimulated cell invasion in breast cancer cells. In addition to a possible role in the induction of thyroid tumourigenesis, PBF overexpression in thyroid cancers inhibits iodide uptake. PBF has been shown to repress sodium iodide symporter (NIS) activity by transcriptional regulation of NIS expression through the human NIS upstream enhancer and further inhibits iodide uptake via a post-translational mechanism of NIS governing subcellular localisation. This review discusses the current data describing PBF expression and function in thyroid cancer and highlights PBF as a novel target for improving radioiodine uptake and thus prognosis in thyroid cancer.
