bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glycyrrhizin induces mineralocorticoid activity through alterations in cortisol metabolism in the human kidney
Authors: Kageyama Y. , Suzuki H. , Saruta T. 
Published: December 2008

ABSTRACT
It has been suggested that the mineralocorticoid action of glycyrrhizin is caused by a defect in the conversion of cortisol to cortisone through inhibition of the enzyme 11β-dehydrogenase (11β-DH). We investigated the functional significance of the inhibition of this enzyme as a mechanism of the mineralocorticoid action of glycyrrhizin. Eighteen healthy volunteers were divided into three groups of six and treated as follows: (1) 225 mg glycyrrhizin/day, (2) 0·1 mg 9α-fluorocortisol (FC)/day and (3) 225 mg glycyrrhizin and 1·5 mg dexamethasone/day, all of which were given for 7 days. The administration of glycyrrhizin or FC induced a similar mineralocorticoid effect; specifically, suppression of plasma renin activity, hypokalaemia and kaliuresis. During the concomitant administration of glycyrrhizin and dexamethasone, however, these mineralocorticoid effects were significantly attenuated. During the administration of glycyrrhizin, urinary excretion of cortisol increased without change in the plasma levels of cortisol, while both plasma level and urinary excretion of cortisone decreased. Changes in cortisol metabolism were not observed during the administration of FC. These results demonstrated the functional significance of the inhibition of 11β-DH in the mineralocorticoid activity of glycyrrhizin in man.
Journal of Endocrinology (1992) 135, 147–152
The role of growth hormone, prolactin and insulin-like growth factors in the regulation of rat mammary gland and adipose tissue metabolism during lactation
Authors: Barber M. C. , Clegg R. A. , Finley E. , Vernon R. G. , Flint D. J. 
Published: December 2008

ABSTRACT
Inhibition of prolactin secretion with bromocriptine and neutralization of GH action with a specific antiserum to rat GH (rGH) were used to explore the modes of action of GH and prolactin in maintaining lactation in the rat. Treatment of dams with anti-rGH caused a small reduction in litter weight gain whilst bromocriptine reduced litter weight gain by 50%. When both treatments were combined, however, milk yield ceased completely and this wasaccompanied by a wide variety of effects on mammary lipid metabolism including decreases in the mRNA concentrations of acetyl CoA carboxylase, fatty acid synthase, malic enzyme and lipoprotein lipase. Activities of acetyl CoA carboxylase and lipoprotein lipase were also significantly reduced. Reciprocal changes were evident in adipose tissue with increases in acetyl CoA carboxylase and lipoprotein lipase activities. In conjunction with a decreased lipolytic response to noradrenaline in adipose tissue of animals given the combined treatment of bromocriptine and anti-rGH, this represented a co-ordinated series of changes to reduce lipid synthesis in the mammary gland and enhance lipogenesis and triglyceride storage in adipose tissue as milk production ceased. All of these effects could be prevented in part by concurrent treatment with GH, but insulin-like growth factor-I (IGF-I) and IGF-II failed to affect any of the parameters measured. Taken as a whole, these data suggest that (1) both prolactin and GH induce a co-ordinated series of changes in the mammary gland, (2) the intracellular controls involved clearly operate at the level of gene transcription although post-translational controls are also probably involved, (3) the effects of GH on the mammary gland could not be mimicked by IGFs and (4) although GH clearly regulates lipid metabolism in adipose tissue in a manner which should favour nutrient utilization by the mammary gland, these effects are probably too small to account for the effects of GH on milk production. Since GH receptors have not been reported to be present on mammary secretory cells, the precise mode of action of GH remains uncertain.
Journal of Endocrinology (1992) 135, 195–202
In-vivo regulation of messenger RNA encoding insulin-like growth factor-I (IGF-I) and its receptor by diabetes, insulin and IGF-I in rat muscle
Authors: Bornfeldt K. E. , Skottner A. , Arnqvist H. J. 
Published: December 2008

ABSTRACT
The effects of continuous or acute administration of insulin or insulin-like growth factor-I (IGF-I) on IGF-I mRNA and IGF-I receptor mRNA were studied in the skeletal muscle (gastrocnemius), heart muscle and vascular smooth muscle (aorta) of non-diabetic and diabetic rats using a solution hybridization assay. The levels of IGF-I mRNA in the different types of muscle markedly decreased by diabetes, whereas changes in IGF-I receptor mRNA were less consistent. Continuous infusion of diabetic rats with insulin (28 or 35 nmol/day) for 4 days normalized the altered levels of IGF-I mRNA and IGF-1 receptor mRNA. Infusion of equimolar concentrations of IGF-I did not affect IGF-I mRNA, but decreased the level of IGF-I receptor mRNA in skeletal muscle.
In acute experiments, rats were injected with equipotent blood glucose-lowering doses of insulin (14 nmol) or IGF-I (107 nmol). Insulin did not significantly affect levels of IGF-I mRNA, but decreased levels of IGF-I receptor mRNA in skeletal muscle and aorta. IGF-I increased levels of IGF-I mRNA in heart muscle, and markedly decreased levels of IGF-I receptor mRNA in skeletal muscle and heart muscle from non-diabetic and diabetic rats.
In conclusion, exogenous IGF-I and insulin can increase IGF-I mRNA and decrease IGF-I receptor mRNA, indicating that both insulin and IGF-I can act as regulators of the IGF-I system in muscle in vivo.
Journal of Endocrinology (1992) 135, 203–211
Effects of insulin, glucocorticoids and thyroid hormones on the activities of key enzymes of glycolysis, glutaminolysis, the pentose-phosphate pathway and the Krebs cycle in rat macrophages
Authors: Costa Rosa L. F. B. P. , Cury Y. , Curi R. 
Published: December 2008

ABSTRACT
In the present study the effects of insulin, glucocorticoids and thyroid hormones on macrophage metabolism and function were investigated. The maximum activities of hexokinase, glucose-6-phosphate dehydrogenase, glutaminase and citrate synthase were determined in macrophages obtained from hormonetreated rats and those cultured for a period of 48 h in the presence of hormones. Macrophage phagocytosis was markedly inhibited by dexamethasone and thyroid hormones, remaining unchanged when insulin was added to the culture medium, however. The changes in the enzyme activities caused by hormone treatments of the rats were very similar to those found in culture. Insulin enhanced citrate synthase and hexokinase activities and diminished those of glutaminase and glucose-6-phosphate dehydrogenase. Dexamethasone had a similar effect except on glucose6-phosphate dehydrogenase. The addition of thyroid hormones to the culture medium raised the activities of glutaminase and hexokinase and reduced that of citrate synthase. The results presented support the suggestion that the effects of insulin, glucocorticoids and thyroid hormones on immune and inflammatory responses could well be mediated through changes in macrophage metabolism..
Journal of Endocrinology (1992) 135, 213–219
Regulation of adrenal steroidogenesis by adrenaline expression of cytochrome P450 genes
Authors: Güse-Behling H. , Ehrhart-Bornstein M. , Bornstein S. R. , Waterman M. R. , Scherbaum W. A. , Adler G. 
Published: December 2008

ABSTRACT
The effect of adrenaline on the secretion of cortisol and cyclic AMP (cAMP) and on the accumulation of four different mRNAs encoding cholesterol side-chain cleavage cytochrome P450 (P450scc), 17α-hydroxylase cytochrome P450 (P45017α), 21-hydroxylase cytochrome P450 (P450c21) and 11β-hydroxylase cytochrome P450 (P45011β) was studied in bovine adrenocortical cells in primary culture and compared with the effects of ACTH. Treatment of cultured cells with adrenaline (1–100 μmol/l) showed a biphasic response in cortisol release over 1–24 h. Concentration of cAMP in the culture media increased from a basal level of <0·06 pmol/dish to a maximal level of 40·14 ± 8·9 pmol/dish with a half-maximal release of 20·07 pmol cAMP/dish in the medium reached 1·2 h after treatment with 10 μmol adrenaline/l. This stimulation resulted in an uniform increase in the levels of all four P450 mRNAs as revealed by Northern blot analysis. Increasing doses of adrenaline produced a maximal mRNA accumulation at a concentration of 10 μmol adrenaline/l. Incubation of the cells with 10 μmol adrenaline/l for 1–24 h produced a biphasic time-course with a half-maximal stimulation after about 5–6 h. Maximal stimulation with ACTH (100 nmol/l) caused different accumulations of the four mRNAs: P450sec mRNA increased twice as much and P45017α mRNA six times as much as the accumulation of P450c21 mRNA and P45011β mRNA, which was about ten-fold over basal values. Propranolol totally blocked the stimulatory effect of adrenaline but not the effect of ACTH. Our data suggest that the stimulatory effect of adrenaline upon de-novo cortisol formation is regulated in part at the transcriptional level in a dose- and time-dependent manner. The regulation requires β-adrenergic receptors and is due to a cAMP-mediated increase in the accumulation of all four P450 mRNAs.
Journal of Endocrinology (1992) 135, 229–237
Antiuterotrophic effects of a pure antioestrogen, ICI 182,780: magnetic resonance imaging of the uterus in ovariectomized monkeys
Authors: Dukes M. , Miller D. , Wakeling A. E. , Waterton J. C. 
Published: December 2008

ABSTRACT
ICI 182,780 is a potent specific pure antioestrogen which may offer advantages in breast cancer treatment compared with partial agonists like tamoxifen. To characterize further the potency and efficacy of ICI 182,780, its effects on the uterus of ovariectomized, oestrogen-treated monkeys (Macaca nemestrina) have been measured using magnetic resonance imaging (MRI). Quantitative MRI allows accurate non-invasive repetitive measurements of endometrial and myometrial volume following hormonal treatments, using each animal as its own control. Single i.m. injections of a long-acting oil-based formulation of ICI 182,780 sustained blockade of oestradiol action on the monkey uterus in a dose-dependent manner for 3–6 weeks. Repeated injections of 4 mg ICI 182,780/kg at 4-weekly intervals provided increasingly effective blockade of uterine proliferation. In a short-acting formulation, ICI 182,780 also completely blocked the trophic action of oestradiol, administered concurrently, in ovariectomized monkeys. Similarly, ICI 182,780 caused involution of the uterus stimulated by prior treatment with oestradiol. The rate and extent of uterine involution in monkeys treated with ICI 182,780 was similar to that seen following oestrogen withdrawal. These studies demonstrate that ICI 182,780 is a fully effective pure antioestrogen in a primate.
Journal of Endocrinology (1992) 135, 239–247
A comparison of the uterotrophic response in cyclic and ovariectomized normotensive and spontaneously hypertensive rats
Authors: Kerr M. B. , Marshall K. , Senior J. 
Published: December 2008

ABSTRACT
The uterotrophic response in the normotensive (CD) and the hypertensive (SHR) rat was compared in intact cyclic rats and in ovariectomized rats given oestradiol. The parameters measured were blood flow, and uterine wet and dry weights. In the cyclic animals blood flow to the oestogen target tissue varied throughout the oestrous cycle, peak flows being achieved at pro-oestrus; in the SHR rat, however, the pro-oestrous maximum was significantly attenuated compared with the CD rat. Uterine wet and dry weights were similar.
The temporal response to oestradiol in ovariectomized rats showed that in the CD rat the hyperaemic response peaked earlier than in the SHR rat, significant changes in terms of increased water imbibition also occurred more quickly in the CD strain. In both strains, uterine dry weight was the last parameter to be significantly increased, the maximum weight being attained more quickly in the SHR rat.
The results of this study indicated that it is the blood flow to the oestrogen target tissues of the uterus and vagina that is most susceptible to change with strain of rat.
Journal of Endocrinology (1992) 135, 263–269
Fine structure of adrenal cortex in rats harbouring a medullary thyroid carcinoma transfected with a corticotrophin-releasing hormone cDNA expression vector
Authors: Feinmesser M. , Asa S. L. , Kovacs K. , Low M. J. 
Published: December 2008

ABSTRACT
We report the light microscopic, transmission and scanning electron microscopic features of the adrenal cortices in rats bearing a medullary thyroid carcinoma cell line transfected with a corticotrophin-releasing hormone (CRH) cDNA expression vector. The animals had elevated CRH, ACTH and corticosterone blood levels, involuted thymuses and markedly enlarged adrenal glands with prominent lipid-depleted cortices and dilated congested capillaries, similar to those of animals treated with ACTH. Using electron microscopy it was found that the enlarged fasciculata and reticularis zones were composed of large, compact cells with abundant smooth endoplasmic reticulum, prominent Golgi complexes, increased number of large mitochondria with focal loss of cristae and cavitation of the internal compartments, numerous lysosomes and prominent elongated microvilli. In addition, small cytoplasmic fragments were seen within the capillary lumina; these structures resembled microvilli that were apparently detached from adrenocortical cells and entered the blood stream via discontinuous endothelium of dilated capillaries. By scanning electron microscopy it was found that the cells had bulging surfaces with scattered pits and numerous long microvilli pointing in different directions.
This animal model allows analysis of the effects of protracted CRH excess resembling tumoural CRH-dependent Cushing's syndrome in human patients. Our findings call attention to the role of microvilli in adrenocortical secretion. The increased number and size of microvilli has been thought to lead to an increase in the surface area of adrenocortical cells, thereby facilitating hormone discharge. The detachment of microvilli from adrenocortical cells may represent a form of apocrine secretion and may contribute to hypercorticosteronaemia in CRH excess.
Journal of Endocrinology (1992) 135, 271–277
A polyclonal antibody to the rat oestrogen receptor expressed in Escherichia coli: characterization and application to immunohistochemistry
Authors: Okamura H. , Yamamoto K. , Hayashi S. , Kuroiwa A. , Muramatsu M. 
Published: December 2008

ABSTRACT
A rat oestrogen receptor-β-galactosidase fusion protein was expressed using a pEX2/rat oestrogen receptor cDNA construct. Scatchard analysis of [3H]oestradiol-17β binding to the cell lysate revealed that the fusion protein had functional binding sites specific for oestradiol with a dissociation constant of 1·49 nmol/l. The relative molecular weight (Mr) of the fusion protein was determined as 180 000 by immunoblot analysis of the cell lysate employing a monoclonal antibody to the human oestrogen receptor.
The protein was isolated by means of SDS-PAGE and subsequent electroblotting. By immunization with the purified materials on nitrocellulose membrane, a polyclonal antibody to the rat oestrogen receptor was raised in a rabbit. Binding of [3H]oestradiol to the oestrogen receptor from the rat uterus was inhibited by the antibody in a dose-dependent manner. The antibody was also able to recognize the oestrogen receptor occupied by [3H]oestradiol. Thus, the antibody could react with both forms of the receptor molecule, either occupied or unoccupied by the hormone. In immunoblot analysis of the cytosol fraction of the rat uterus, a single band of Mr 67 000, the size of the oestrogen receptor, was detected by the antibody. Moreover, when the antibody was applied to immunohistochemical examination of paraffin-embedded pituitary and brain sections of the rat, immunostaining was observed in cells of the anterior pituitary and in neurones in specific regions of the brain. The immunoreactivity was restricted exclusively to cell nuclei in both tissues.
These results demonstrate that the polyclonal antibody obtained in the present study was specific to the oestrogen receptor, and that it would be a powerful tool to detect and analyse the receptors in various target tissues for oestrogen.
Journal of Endocrinology (1992) 135, 333–341
Inhibition of bovine adrenocortical steroidogenesis by benzodiazepines: a direct effect on microsomal hydroxylation or an inhibition of calcium uptake?
Authors: Thomson I. , Fraser R. , Kenyon C. J. 
Published: December 2008

ABSTRACT
We have previously reported that benzodiazepines inhibit microsomal steroid hydroxylases. We have now studied their effects at much lower drug concentrations and have also addressed the suggestion that benzodiazepines alter cellular calcium metabolism.
We investigated the in-vitro effects of midazolam on microsomal steroid hydroxylation by measuring basal and ACTH-stimulated cortisol and 17α-hydroxyprogesterone (17-OHP) synthesis. Threshold inhibition of basal cortisol production was achieved by 3·4 μmol midazolam/1 while ACTH-stimulated production required 13·6 μmol/l. This was accompanied by a biphasic response of 17-OHP production, rising to a maximum at 13·6 μmol midazolam/l for basal and 6·8 μmol midazolam/l for ACTH-stimulated synthesis suggesting a preferential inhibitory effect on 21-hydroxylase activity at < 6·8 μmol/l and additonal effects on 17α-hydroxylation at higher drug concentrations. This explains the inhibition of ACTH-stimulated cortisol synthesis by midazolam (50% inhibitor dose (IC50) 22 μmol/l). Using 21-deoxycortisol as substrate, we have demonstrated that midazolam is a competitive inhibitor of 21-hydroxylase (inhibitory constant (KI) 35 μmol/l).
Both midazolam and diazepam inhibited K+-stimulated aldosterone synthesis, with IC50 values of 1·2 μmol/l and 0·8 μmol/l respectively, which are far lower than those observed for ACTH-stimulated cortisol synthesis. With 11β-hydroxyprogesterone as substrate, the KI for the inhibition of aldosterone synthesis by midazolam was 54 μmol/l. Potassium stimulates aldosterone biosynthesis at least partly by changing intracellular free calcium levels. To investigate possible antagonistic effects of benzodiazepines on calcium metabolism, we measured 45Ca uptake in the presence of midazolam. Both basal (P < 0·01) and K+-stimulated 45Ca uptake (P < 0·05) were inhibited by the drug although the effects of K+ were not completely abolished. Comparison of the dose-dependent effects of midazolam on basal 45Ca uptake in cell suspensions prepared from different areas of the adrenal cortex indicated that zona glomerulosa cells are more sensitive to midazolam.
We confirm that benzodiazepines at low concentrations have a direct effect on microsomal steroid hydroxylase enzymes in vitro and postulate that the greater sensitivity to benzodiazepines of K+-stimulated aldosterone synthesis, when compared with either ACTH-stimulated cortisol synthesis or conversion of 21-deoxycortisol to cortisol, may be explained by additional effects of these drugs on plasma membrane calcium transport.
Journal of Endocrinology (1992) 135, 361–369
Restoration of juvenile baseline growth hormone secretion with preservation of the ultradian growth hormone rhythm by continuous delivery of growth hormone-releasing factor
Authors: Vasilatos-Younken R. , Tsao P. H. , Foster D. N. , Smiley D. L. , Bryant H. , Heiman M. L. 
Published: December 2008

ABSTRACT
The ability of continuously delivered GH-releasing factor (GRF) to enhance GH secretion while maintaining the normal ultradian GH rhythm was investigated. Synthetic human GH-releasing factor (hGRF(1–44)NH2) was continuously infused for 4 days by means of i.v. catheters to 11-week-old broiler chickens. At this age, overall endogenous GH secretion is low, and baseline GH is barely detectable. Six birds per treatment received vehicle (control), 0·324 mg hGRF(1–44)NH2/kg body weight per day (low dose) or 3·24 mg hGRF(1–44)NH2/kg body weight per day (high dose). After 4 days of GRF conditioning, concurrent with continued GRF infusion, serial blood samples were removed via atrial catheters at 15-min intervals for 6 h and GH plasma profiles determined.
High dose GRF significantly increased GH plasma concentrations over tenfold compared with controls; however, most of this increase reflected an increase in basal GH, which was reinstated to juvenile baseline levels. Augmentation of pulse amplitude above this increased baseline was not proportionately as high, and failed to reach juvenile levels. The ultradian rhythm of GH was not altered by continuous GRF administration.
Both low and high dose GRF treatments resulted in significant enlargement of the anterior pituitary gland. Total pituitary GH mRNA levels, although elevated over twofold by GRF treatment, were not significantly different from controls. Measures of plasma GH magnitude (overall and baseline mean, and peak amplitude) were significantly correlated with pituitary GH mRNA for control birds, but were not correlated for GRF treatments.
Feed intake was markedly depressed (33%) on the high dose GRF treatment, in conjunction with total inhibition of body weight gain over the 4-day period of administration. Longitudinal bone growth and width of the epiphyseal growth plate were also significantly reduced by high dose GRF treatment, probably reflecting the reduced level of nutrient intake, despite high circulating concentrations of GH.
Journal of Endocrinology (1992) 135, 371–382
Intracellular pH regulation in human thyrocytes: evidence of both Na+/H+ exchange and Na+-dependent Cl−/HCO−3 exchange
Authors: Kayser L. , Høyer P. E. , Perrild H. , Wood A. M. , Robertson W. R. 
Published: December 2008

ABSTRACT
The present study was undertaken to investigate the regulation of intracellular pH in human thyroid epithelial cells and to characterize the kinetics of the acid-extruding processes operating in the absence and presence of HCO−3, Na+ and Cl−. A dynamic technique of dual excitation microfluorimetry and the pH-sensitive fluorescent probe 2′,7′-bis-(2-carboxyethyl)-5(and-6)-carboxyfluorescein was employed.
The intracellular pH was 7·01 ± 0·27 (n = 29) and 6·94 ± 0·25 (n = 54) in the absence and presence of HCO−3 respectively. Both in the absence and presence of HCO−3, the recovery from intracellular acid loads was not only due to an Na+/H+ exchange, but also to an Na+-dependent HCO−3/Cl− exchange. In alkaline conditions caused by NH4Cl pulsing, an HCO−3/Cl− exchange was also found. The cells in HCO−3 responded with a wide range of maximal hydrogen efflux rates in experiments where cells were either pretreated with 4,4′-diisothiocyanatostilbene-2,2′-disulphonic acid or incubated with amiloride. The heterogeneity might be due to subpopulations of thyrocytes in different metabolic states or at different points in the cell cycle.
It is concluded that recovery from intracellular acidification in human thyroid cells is due to both Na+/H+ exchange and Na+-dependent Cl−/HCO−3 exchange even in nominally HCO−3-free conditions, and that recovery from intracellular alkalinization is due to a Cl−/HCO−3 exchange which needs to be characterized further.
Journal of Endocrinology (1992) 135, 391–401