bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thyroidal regulation of nuclear tri-iodothyronine receptors in the developing rat testis
Authors: Palmero S. , Prati M. , De Marco P. , Trucchi P. , Fugassa E. 
Published: December 2008

ABSTRACT
Previous work has demonstrated that thyroid hormones influence testis development. Specific receptors for tri-iodothyronine (T3) have been demonstrated in Sertoli cells. The aim of the present study was to examine the possible effect of thyroid hormone on its own receptor during pubertal development by evaluating the influence of thyroid status on T3-binding capacity, -binding affinity and receptor occupancy in nuclei isolated from immature rat testes. The binding capacity for T3 of nuclei from rat testis significantly decreased during pubertal development, being 375±32, 117±15 and 44±7 fmol/mg DNA in 7-, 21-and 35-day-old rats respectively, whereas the affinity of binding, as evaluated by the dissociation constant (Kd), did not change. Early induced hypothyroidism significantly affected the time-course of the postnatal decline of nuclear T3 receptors in the testis. At 21 days of age, the binding capacity for T3 in the testis of methimazole-treated rats was significantly higher with respect to euthyroid controls, being 173 ±21 and 117 ± 15 mol/mg DNA respectively, while the Kd was unaffected. T3 replacement therapy completely prevented changes in T3 receptor number induced by hypothyroidism without modifying the Kd. Our results indicate that nuclear T3 receptors in the developing rat testis are modulated by thyroid hormone.
Journal of Endocrinology (1993) 136, 277–282
The regulation of oxidative drug metabolism by growth hormone in the dwarf goat: differences from and similarities to the mechanisms in rats
Authors: Witkamp R. F. , Nijmeijer S. M. , Van Duin C. T. M. , Noordhoek J. , Van Miert A. S. J. P. A. M. 
Published: December 2008

ABSTRACT
The effects of bovine GH (BST), administered in different dose patterns, on in-vivo oxidative drug metabolism, were studied in female dwarf goats. Animals received recombinantly derived methionyl BST at a dose of 500 μg/kg body weight per 24 h for 6 days. It was administered to one group of goats as one s.c. injection per day, another group received a similar 24-h dose divided into three s.c. injections given at 8-h intervals, and the third group received 50 μg BST/kg body weight every 2·5 h by a pulsative i.v. infusion. Oxidative metabolic capacity was assessed by determining plasma sulphadimidine (SDD) elimination and urinary metabolite excretion. SDD shows a marked sex-dependent plasma elimination in dwarf goats, with male goats having a lower plasma clearance than female goats. When BST was given by daily injection, no clear effects on SDD plasma clearance or urinary metabolite excretion were observed. However, when the total dose was divided into three injections given at 8-h intervals, the plasma SDD elimination rate decreased. This was associated with a decrease in urinary excretion of the two main hydroxy SDD metabolites. When BST was given by discontinuous i.v. infusion, simulating the male endogenous plasma GH pattern, a marked decrease in SDD plasma clearance was observed. In addition, the excretion of the two urinary hydroxy metabolites was considerably reduced. These results suggest that GH can affect drug oxidation in dwarf goats via mechanisms similar to those suggested for rats. However, in the dwarf goat, the sex differences in drug metabolism are opposite to those in rats.
Journal of Endocrinology (1993) 136, 313–317
Short-term endocrine consequences of total body irradiation and bone marrow transplantation in children treated for leukemia
Authors: Ryalls M. , Spoudeas H. A. , Hindmarsh P. C. , Matthews D. R. , Tait D. M. , Meller S. T. , Brook C. G. D. 
Published: December 2008

ABSTRACT
We studied 24-h hormone profiles and hormonal responses to insulin-induced hypoglycaemia prospectively in 23 children of similar age and pubertal stage, nine of whom had received prior cranial irradiation (group 1) and fourteen of whom had not (group 2), before and 6–12 months after total body irradiation (TBI) for bone marrow transplantation in leukaemia.
Fourier transformation demonstrated that group 1 children had a faster periodicity of GH secretion before TBI than group 2 children (160 vs 200 min) but the amplitude of their GH peaks was similar. There were no differences between the groups in circadian cortisol rhythm, serum concentrations of insulin-like growth factor-I (IGF-I), sex steroids and basal thyroxine (T4). The peak serum GH concentrations observed after insulin-induced hypoglycaemia were similar between the two groups but the majority of patients had blunted responses.
TBI increased the periodicity of GH secretion in both groups (group 1 vs group 2; 140 vs 180 min), but the tendency to attenuation of amplitude was not significant. There were no significant changes in the peak serum GH concentration response to insulin-induced hypoglycaemia which remained blunted. Serum IGF-I, sex steroid, cortisol or T4 concentrations were unchanged.
Low-dose cranial irradiation has an effect on GH secretion affecting predominantly frequency modulation leading to fast frequency, normal amplitude GH pulsatility. This change is accentuated by TBI. In patients with leukemia, there is a marked discordance between the peak serum GH response to insulin-induced hypoglycaemia compared with the release of GH during 24-h studies, irrespective of the therapeutic regimen used. Pharmacological assessment of GH reserve needs to be interpreted with caution in such situations.
Journal of Endocrinology (1993) 136, 331–338
Reduction of cyclic AMP in the sciatic nerve of rats made diabetic with streptozotocin and the mechanism involved
Authors: Shindo H. , Tawata M. , Onaya T. 
Published: December 2008

ABSTRACT
We have investigated the relationship between cyclic nucleotides and nerve function in the sciatic nerve of rats made diabetic with streptozotocin. Cyclic AMP (cAMP) content in the sciatic nerves of diabetic rats was significantly (P < 0·05) lower than in those of normal rats, while cyclic GMP content did not differ between the two groups. Administration of the stable prostacyclin analogue iloprost or dibutyryl cyclic AMP (dbcAMP) significantly (P<0·05) restored the cAMP content in the sciatic nerves and motor nerve conduction velocity, which reflects nerve function. There was a positive correlation between cAMP content in the sciatic nerves and motor nerve conduction velocity in both normal and diabetic rats.
Endoneurial preparations of sciatic nerves obtained from normal rats were incubated in Krebs–Ringer bicarbonate buffer containing d-glucose (30 or 5·5 mmol/l). Cyclic AMP accumulation was significantly (P<0·05) suppressed in the buffer containing 30 mmol d-glucose/l compared with that containing 5·5 mmol/l. Iloprost (P<0·05) and dbcAMP (P<0·01) increased cAMP accumulations in the tissues incubated in buffer containing both 5·5 and 30 mmol d-glucose/l. When non-metabolizing hexoses, such as l-glucose or 3-O-methylglucose instead of d-glucose were used, cAMP accumulations at 30 mmol hexose/1 were not significantly different from those at 5·5 mmol/l.
Cyclic AMP phosphodiesterase activity in the sciatic nerves of diabetic rats did not change compared with that in nerves from normal rats. Although not significant, mean ATP content in the sciatic nerves of diabetic rats was about 30% lower than that in nerves of normal rats. Basal, iloprost-stimulated and forskolin-stimulated adenylate cyclase activities in the sciatic nerves of diabetic rats were significantly (P<0·05) reduced when compared with those of control rats.
We therefore conclude that reduction of cAMP content in peripheral nerves may be involved in the pathogenesis of diabetic neuropathy and is mainly caused by the impairment of adenylate cyclase activity in the diabetic state.
Journal of Endocrinology (1993) 136, 431–438
The 11β-hydroxysteroid dehydrogenase inhibitor glycyrrhetinic acid affects corticosteroid feedback regulation of hypothalamic corticotrophin-releasing peptides in rats
Authors: Seckl J. R. , Dow R. C. , Low S. C. , Edwards C. R. W. , Fink G. 
Published: December 2008

ABSTRACT
Steroid-metabolizing enzymes modulate the effects of androgens on brain differentiation and function, but no similar enzymatic system has been demonstrated for adrenocorticosteroids which exert feedback control on the hypothalamus. 11β-Hydroxysteroid dehydrogenase (11β-OHSD) rapidly metabolizes physiological glucocorticoids (corticosterone, cortisol) to inactive products, thereby regulating glucocorticoid access to peripheral mineralocorticoid and glucocorticoid receptors in a site-specific manner. Using in-situ hybridization, we found expression of 11β-OHSD mRNA in neurones of the hypothalamic paraventricular nucleus (PVN) where corticotrophinreleasing factor-41 (CRF-41) is synthesized and from where it is released into hypophysial portal blood. Administration of glycyrrhetinic acid (GE), a potent 11β-OHSD inhibitor, decreased CRF-41 release into hypophysial portal blood in the presence of unchanged circulating glucocorticoid levels, suggesting that 11β-OHSD regulates the effective corticosterone feedback signal to CRF-41 neurones. These effects of GE were not observed in adrenalectomized animals, demonstrating dependence on adrenal products. In contrast, GE led to two- to threefold increases in arginine vasopressin and oxytocin release into portal blood, effects also dependent upon intact adrenal glands. These results suggest that 11β-OHSD in the PVN, and possibly other sites, may represent a novel and important control point of corticosteroid feedback on CRF-41 release in vivo.
Journal of Endocrinology (1993) 136, 471–477
The effects of dexamethasone treatment on immunoreactive and bioactive insulin-like growth factors (IGFs) and IGF-binding proteins in normal male volunteers
Authors: Miell J. P. , Taylor A. M. , Jones J. , Holly J. M. P. , Gaillard R. C. , Pralong F. P. , Ross R. J. M. , Blum W. F. 
Published: December 2008

ABSTRACT
Glucocorticoids inhibit somatic growth in man and laboratory animals, and have long been regarded as suppressors of both stimulated GH secretion and insulin-like growth factor (IGF) activity. Recent evidence suggests, however, that glucocorticoids can be potent GH secretagogues in their own right with concomitant increases in circulating IGF-I levels. IGFs circulate tightly bound to a group of high-affinity binding proteins (IGFBPs) which modulate their actions. In order to investigate the effects of glucocorticoids on serum levels of IGFs and IGFBPs, normal male volunteers were sampled over 24-h periods before and directly after treatment with dexamethasone (2 mg twice daily) for 96 h. Following dexamethasone administration, all volunteers showed a marked increase in mean± s.e.m. IGF-I levels over the 24-h sampling period (292·2±31·8 before dexamethasone, 425·9 ±37 μg/l after dexamethasone, P<0·005); there was no change in mean IGF-II levels. Integrated mean insulin levels were raised by dexamethasone treatment (50 ±4·6 before dexamethasone, 117±13·4 mU/l after dexamethasone, P= 0·002) and IGFBP-1 was significantly suppressed (42·9±8·2) before dexamethasone, 28·0±7·9 μg/l after dexamethasone, P<0·001). IGFBP-2 levels were similarly suppressed after dexamethasone (319·5±24·5 before dexamethasone, 214·8±8·5 μg/l after dexamethasone, P=0·002), and there was a significant increase in IGFBP-3 levels from 3·24 ±0·25 to 3·67±0·32 mg/l (P=0·0153). Mean IGF bioactivity over the sampling period after dexamethasone was reduced by approximately 60% (0·93 ±0·39 before dexamethasone, 0·39 ±0·05 U/ml after dexamethasone, P <0·0001).
There were strong negative correlations between both insulin and IGF-I levels and those of IGFBP-2, suggesting the presence of a novel regulation mechanism for this binding protein. The established inverse relationship between insulin and IGFBP-1 was maintained after dexamethasone. These results suggest that glucocorticoids alter the bioactivity of IGFs, possibly by induction of inhibitors, but that neither IGFBP-1 nor IGFBP-2 can be implicated as glucocorticoiddependent inhibitors of IGF bioactivity in man. The study also demonstrates for the first time a strong negative correlation between IGF-I, insulin and IGFBP-2.
Journal of Endocrinology (1993) 136, 525–533
Differential regulation of FSH and inhibin gene expression and synthesis by testosterone in immature and mature male rats
Authors: Perheentupa A. , Bergendahl M. , de Jong F. H. , Huhtaniemi I. 
Published: December 2008

ABSTRACT
Direct effects of testosterone on gonadotrophins at the pituitary level were studied in intact and castrated immature (age 10 days) and mature (70 days) male rats. Gonadotrophin-releasing hormone action was blocked by treatment with a potent GnRH antagonist, Ac-d-pClPhe-d-pClPhe-d-Trp-Ser-Tyr-d-Arg-Leu-Arg-Pro-d-Ala-NH2CH3COOH (Ant; Organon 30276; 1·0 mg/kg body weight per day) injected subcutaneously. Silicone elastomer capsules were used for the testosterone treatment. Both treatments commenced on the day of orchiectomy and lasted for 7 days. In adult male rats Ant treatment suppressed serum testosterone from 9·5 ± 2·5 (s.e.m.) nmol/l to below the limit of detection (< 0·10 nmol/l; P < 0·01), and the testosterone implants reversed the decrease. Treatment with Ant decreased the pituitary content of FSH-β subunit mRNA in intact and orchiectomized rats to 14% of their respective controls (P < 0·01). These levels were increased to 80–81% of controls (not significant) in both groups by combined treatment with testosterone and Ant. Orchiectomy alone increased FSH-β subunit mRNA by 202% (P < 0·01). In intact immature rats Ant treatment decreased the level of pituitary FSH-β subunit mRNA to 21% (P<0·01), and a partial recovery (P < 0·01) to 42% of controls was observed with combined Ant + testosterone treatment. In contrast, in orchiectomized immature rats, where ANT decreased FSH-β subunit levels to 48% of controls (P < 0·01), testosterone was able to reverse these mRNA levels completely (114% of controls). No evidence for the direct pituitary effects of testosterone were found in the mRNA of the common α or LH-β subunits. In adult rats, the testicular inhibin α and βA subunit mRNA levels were increased (P < 0·01) by Ant + testosterone compared with Ant-treated animals, but there were no differences in serum immunoreactive inhibin between any of the uncastrated adult groups. In intact immature rats, Ant + testosterone treatment increased (P < 0·01) inhibin βA subunit mRNA levels compared with controls and Ant-treated animals. Ant decreased the level of peripheral inhibin immunoreactivity from 8·3 ± 2·0 U/ml to 2·1 ± 0·4 U/ml (P < 0·01) and testosterone reversed it to 5·8 ± 0·6 U/ml (not significant).
In conclusion, our observations indicated that testosterone is able to stimulate FSH gene expression and secretion directly in immature and adult rats, but the testosterone response is enhanced at both ages by orchiectomy, even more so in the immature rat. This may be explained by age differences in the contribution of testicular inhibin to the regulation of FSH synthesis and secretion at the pituitary level.
Journal of Endocrinology (1993) 137, 69–79
Growth hormone receptor gene expression in sex-linked dwarf Leghorn chickens: evidence against a gene deletion
Authors: Hull K. L. , Fraser R. A. , Marsh J. A. , Harvey S. 
Published: December 2008

ABSTRACT
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.
Journal of Endocrinology (1993) 137, 91–98
Steroidal interactions in the ageing endocrine system: absence of suppression and pathology in reproductive systems of old males from a mixed-sex socially stressful rat colony
Authors: Taylor G. T. , Bardgett M. , Farr S. , Womack S. , Komitowski D. , Weiss J. 
Published: December 2008

ABSTRACT
A paradigm using chronic social stress and multiple measures of the reproductive system were used to assess changes with ageing in the dynamics of endogenous steroid interactions. The 22- to 24-month-old male rats lived for 8 weeks in one of four types of colony, in groups of the same sex or groups of mixed sex including familiar or unfamiliar old males. Measures of endocrinology (circulating steroid levels), behaviour (exploration and sociosexual responses), physiology (body and organ weights and epididymal sperm count) and histology (adrenal and ventral prostate glands) served as markers of activation of the hypothalamic-pituitary-adrenal (HPA) or hypothalamic-pituitary-testicular (HPT) axes. Old males living under stable conditions as familiar same-sex colonies served as the comparison group. Results indicated clear chronic activation of the HPA axis in the unfamiliar all-male colonies and of the HPT axis in the familiar males from mixed-sex colonies, whereas both steroidal axes were stimulated in colonies of unfamiliar males and females. Findings from aged males under chronic stress suggested that reproductive dysfunction may be limited to situations in which activation of the HPA axis occurs without concurrent stimulation of the HPT axis. Data on steroidal interactions from mixed-sex groups suggested that (1) chronic excitation of the HPA failed to suppress function in the reproductive system of the old males, (2) their stress responses were little affected by chronic HPT activation and (3) there was no evidence for stress-induced pathology, even in the vulnerable prostate gland. The conclusion is that increased risks for urogenital pathology with long-term exposure to stress is not an inevitable outcome for ageing male rats nor, perhaps, for other social species living under conditions in which multiple endocrine systems typically undergo simultaneous activation.
Journal of Endocrinology (1993) 137, 115–122
Measurement of insulin-like growth factor-II in human plasma using a specific monoclonal antibody-based two-site immunoradiometric assay
Authors: Crosby S. R. , Anderton C. D. , Westwood M. , Holly J. M. P. , Cwyfan Hughes S. C. , Gibson M. , Morrison C. A. , Young R. J. , White A. 
Published: December 2008

ABSTRACT
An immunoradiometric assay (IRMA) for the measurement of insulin-like growth factor-II (IGF-II) in human plasma has been developed, optimized and evaluated clinically in normal subjects and patients with disorders of the GH/IGF-I axis. Six monoclonal antibodies (MAbs) to recombinant human IGF-II (rhIGF-II) were produced, all of which had low cross-reactivity with rhIGF-I (< 0·01%) and insulin (< 0·01%). Compatibility of pairs of MAbs was tested in two-site IRMAs using three radioiodinated MAbs and three MAbs linked to Sephacryl S-300 (with separation of bound and free radiolabelled MAb by sucrose layering). Seven pairs of MAbs bound rhIGF-II and the combination of 125I-labelled W3D9 and W2H1 linked to solid phase was selected. The optimized assay had a completion time of 4 h, a minimum detection limit of 30 ng/ml (2·5 standard deviations from the zero standard) and detected a single peak of endogenous IGF-II in normal plasma which co-eluted with rhIGF-II after acid gel chromatography.
IGF-II was measured in formic acid/acetone extracts of plasma from 16 normal subjects (mean 685, range 516–1008 μg/l), four acromegalic patients (mean 637, range 553–700 μg/l), fourteen patients with type-1 diabetes (mean 635, range 247–753 μg/l), nine patients with uraemia (mean 423, range 78–850 μg/l), and three patients with Laron-type GH insensitivity (75, 35 and 36 μg/l). No significant fluctuations were detected between samples obtained hourly from 08.00 to 19.00 h in normal subjects.
Low levels of IGF-binding proteins (IGFBPs) remaining in plasma extracts may interfere with the measurement of IGF-II and give rise to falsely elevated IGF-II levels in radioimmunoassays or falsely suppressed levels in IRMAs. Such interference did not occur with the IRMA when used to measure IGF-II in extracts from normal subjects, acromegalic patients and patients with type-1 diabetes, and the addition of excess rhIGF-I in order to displace IGF-II from residual IGFBPs had no effect on IGF-II measurements in these samples. However, levels of IGF-II measured in extracts from patients with Laron-type GH insensitivity and patients with uraemia increased markedly after preincubation with excess rhIGF-I. The accurate measurement of IGF-II by IRMA in extracts from these subjects therefore requires the displacement of IGF-II from IGFBPs prior to assay. We conclude that, in contrast to radioimmunoassays, the two-site IRMA developed here provides a practical, rapid and specific method for the measurement of IGF-II in human plasma.
Journal of Endocrinology (1993) 137, 141–150
The effect of the blockade of α-melanocyte-stimulating hormone on LH release in the rat
Authors: Caballero C. , Celis M. E. 
Published: December 2008

ABSTRACT
We have investigated the effect of blocking α-MSH on the release of LH in rats at pro-oestrus. Continuous infusion of Pro-Leu-Gly-NH2 (PLG; 0·2 μg/h), from the afternoon of dioestrus-2 until the day of oestrus, inhibited LH at pro-oestrus and the next ovulation on the day of oestrus. Plasma α-MSH levels decreased significantly in rats treated with PLG. This inhibitory effect on LH release was not observed in rats treated with a continuous infusion of a diluted antiserum against α-MSH (0·5 μl/h, diluted 1/10) from the afternoon of dioestrus-2 until the day of oestrus. On the contrary, the administration of undiluted antiserum against α-MSH (0·5 μl/h) blocked LH release and ovulation. The release of α-MSH into the blood was also significantly blocked by this treatment.
When serum levels of progesterone were measured at 12.00 and 14.00 h in rats in which α-MSH release was blocked by PLG or concentrated antiserum, a significant decrease was observed when compared with the levels of progesterone in control rats. These results show that the blockade of α-MSH inhibits LH release and the next ovulation in rats treated with PLG or with concentrated antiserum against α-MSH, through a blockade of progesterone of adrenal origin.
Journal of Endocrinology (1993) 137, 197–202