bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetics and pharmacodynamics of recombinant and urinary human FSH in the male monkey (Macaca fascicularis)
Authors: Weinbauer G F , Simoni M , Hutchison J S , Nieschlag E 
Published: December 2008

Abstract
A dose-finding study was performed in adult male monkeys (Macaca fascicularis) to evaluate the pharmacokinetics and pharmacodynamics of a recombinant human FSH preparation (rhFSH). Groups of five monkeys were randomly assigned to receive single i.m. injections of 0·9% (w/v) NaCl (diluent), 6, 12 or 24 IU rhFSH/kg or 24 IU urinary human FSH/kg (uhFSH). The doses were based on an in vivo ovarian weight gain assay. Blood samples were collected 24 h before and immediately prior to injections, and 4, 8, 12, 24, 72 and 96 h after injections for determination of serum levels of immunoactive FSH by fluoroimmunoassay, bioactive FSH by an in vitro Sertoli cell assay, and inhibin and testosterone by radioimmunoassay. Inhibin was chosen as a marker for in vivo hFSH activity, since the secretion of inhibin in male monkeys is under the control of FSH. Administration of hFSH resulted in dose-related increases in serum hFSH concentrations. rhFSH and uhFSH exhibited similar pharmacokinetics. Comparable findings were obtained when serum samples were analysed for in vitro FSH bioactivity. Maximum serum hFSH levels were obtained 4–6 h after administration and the elimination half-life of hFSH was on average 18–22 h. The serum pharmacokinetics of rhFSH were linear within the dose range explored. Baseline inhibin concentrations varied significantly between groups. However, when the changes in inhibin concentrations were normalized to the baseline values (per cent change, area under curve and maximum inhibin level), a dose-dependent stimulatory effect of rhFSH on serum inhibin was evident. This effect attained statistical significance with doses of 24 IU rhFSH/kg and 24 IU uhFSH/kg, and the serum inhibin responses to rhFSH and uhFSH were not significantly different. No significant differences were observed with regard to the serum concentrations of testosterone between the diluentand hFSH-treated groups. It was concluded that rhFSH is bioactive in terms of stimulating testicular inhibin production in the male monkey and that the pharmacokinetic properties of rhFSH and uhFSH are similar.
Journal of Endocrinology (1994) 141, 113–121
Changes in gonadotrophin secretion during childhood and puberty
Authors: Bridges N A , Matthews D R , Hindmarsh P C , Brook C G D 
Published: December 2008

Abstract
The changes in gonadotrophin secretion in childhood and puberty involve changes in the pulsatile pattern as well as mean concentration. We have examined pulsatile secretion using 24-h LH profiles in 78 children aged 4·2–15·6 years and six adult men. The profiles were analysed by a method which gives an estimate of peak and baseline levels and by spectral analysis. Prepubertal children were divided into groups by age and pubertal children by pubertal stage.
Baseline LH levels in children aged 4·2–6·9 years were higher than in those aged 7·1–9·8 years. Pulse frequency in both groups was slow (periodicities 140–200 min). In the oldest prepubertal group there was an increase in peak levels with increased spectral power at periodicities of 100–120 min. Pulse frequency did not change in puberty (periodicity 120–160 min). Girls demonstrated an increase in both peak and baseline LH concentrations in early puberty. Boys had an increase in only peak levels in early puberty; there was no increase in baseline concentrations until a testicular volume of 10 ml was attained.
In conclusion, these data show that LH levels do not reach a nadir until 8 years of age. We have detected a sex difference in the pattern of LH secretion seen in early puberty, and this mirrors clinical findings. The mature pattern attained by the end of puberty in both sexes is probably important for fertility.
Journal of Endocrinology (1994) 141, 169–176
The appearance and activity of tissue thyroxine 5′- and 5-monodeiodinase during ontogenesis in the fetal pig
Authors: Ślebodziński A B , Brzezińska-Ślebodzińska E 
Published: December 2008

Abstract
The ontogeny of the fetal monodeiodinase systems, during the period before the onset of thyroid activity until birth, has been described only in the rat, rabbit and chick. We have studied 5′- and 5-monodeiodinase activities in the liver, kidney and placenta of pig fetuses, from day 32 of gestation up to birth, and on days 1, 3, 7 and 14 after birth. Fetuses (123) from 15 litters, 32 newborn piglets, 15 sows (mothers) and 10 non-pregnant pigs were used. The relationships between monodeiodinase activities, thyroxine (T4), tri-iodothyronine (T3) and reverse triiodothyronine (rT3) blood serum concentrations and sulphydryl groups (total (T-SH) and non-protein (NP-SH)), were measured.
5′-Monodeiodinase activity (5′-MD type I; converting T4 to T3) and 5-monodeiodinase (5-MD; converting T4 to rT3) were detectable in the liver at the onset of thyroid hormone biosynthesis, and before that time (day 32 of gestation) in the placenta. Liver 5′-MD activity was very low between days 32 and 84 of gestation, and then increased rapidly at about day 93, reaching a maximal value 2 days before term. Activity in the liver (but not in the kidney) was higher than that in maternal, newborn and non-pregnant adult tissue. The increase in NP-SH groups in the liver and kidney and T-SH groups in the placenta during the last 5 days of gestation coincided with the increase in 5′-MD activity. The 5-MD activity of the liver was generally five to ten times lower than that of 5′-MD, being highest on days 65–76 and 65–84 in the kidney and placenta respectively.
Serum T4 concentrations paralleled the steady increase in T4- to T3-converting activity in the kidney and liver, but not in the placenta. Two weeks before birth, fetal T3 concentrations exceeded those of rT3 by a factor of 1·5 or more, indicating that T4 metabolism in the pig is dominated by the activity of 5′-MD. This pattern is different from that in prenatal humans, rats or sheep in which rT3 is the primary circulating T4 metabolite.
Journal of Endocrinology (1994) 141, 243–249
Functional heterogeneity with respect to oestrogen treatment in prolactin cell subpopulations separated by Percoll gradient centrifugation
Authors: Velkeniers B , Kazemzadeh M , Vanhaelst L , Hooghe-Peters E L 
Published: December 2008

Abstract
The effects of oestradiol on prolactin gene expression were studied by quantitative in situ hybridization histochemistry in different prolactin pituitary cell (sub)populations, which had been obtained by separation on a discontinuous Percoll gradient. When cells were incubated in vitro in the presence of oestradiol (10−8 m) for a period of 4, 24, 48 and 72 h, there was an increase in the amount of prolactin mRNA, from 24 h on, only in high-density prolactin cells and lactotrophs of the total cell suspension. In contrast, the amount of prolactin mRNA in lactotrophs of low density did not change upon treatment with oestradiol. Pharmacological treatment with 50 μg oestradiol/day (s.c.) of random cycling female rats in vivo for 14 days increased the total number of prolactin gene-expressing cells and more lactotrophs were recovered at high density after Percoll gradient centrifugation. These results suggest a preferential stimulatory effect of oestradiol on prolactin gene transcription on a subpopulation of lactotrophs. Changes observed in prolactin cell layers after oestradiol treatment in vivo may represent a preferential effect in situ on a particular mammotroph cell subpopulation.
Journal of Endocrinology (1994) 141, 251–258
Blood sampling procedures influence serum calcitonin concentrations in rats
Authors: Feinstein R E , Bucht E , Grimelius L , Iwarsson K , Rönnbäck C , Selking Ö , Sjöstedt U , Sjöberg H -E 
Published: December 2008

Abstract
The aim of this study was to determine whether serum calcitonin (S–CT) in rats is influenced by the method of taking blood samples. Sampling during halothane anaesthesia, after repeated administration of anaesthesia after a 14-day interval, and sampling without the use of anaesthetics (i.e. after the rats were made unconscious by stunning), resulted in different S–CT values (P≤0·001), whereas Ca2+ levels were not affected. In thyroidectomized rats, the S–CT values after stunning were not significantly different whereas those in sham-operated rats were different (P≤0·01). The possibility that anaesthesia may suppress stunning-induced changes in S–CT was explored in three other groups of rats subjected to halothane anaesthesia, stunning and stunning under halothane anaesthesia respectively. Although the S–CT level was highest after stunning and lowest in halothane-anaesthetized rats (P≤0·001), anaesthesia did not suppress the effect of stunning on S–CT. In conclusion the effect of sampling procedures must be considered in studies on the levels of S–CT in rats.
Journal of Endocrinology (1994) 141, 267–270
Intrathyroidal cytokine gene expression profiles in autoimmune thyroiditis
Authors: Paschke R , Schuppert F , Taton M , Velu T 
Published: December 2008

Abstract
Cytokines are thought to mediate the initiation and perpetuation of autoimmune thyroiditis. However, this concept is mainly based on in vitro findings and to date only interleukin (IL)-6 and interferon-γ (IFN-γ) have been detected in Graves' disease in vivo. The cytokine pattern produced by T-helper (Th) cells has important regulatory effects on the nature of the immune response. We therefore determined these cytokine mRNAs in Graves' disease and Hashimoto's thyroiditis.
RNA was extracted by cesium chloride gradient centrifugation from the thyroid tissue of 12 patients undergoing thyroid resection for Graves' disease and from two patients being treated for Hashimoto's thyroiditis. Two patients with parathyroid adenomas and one patient with a goiter were used as controls. RNA was also extracted from normal human thyroid epithelial cells in primary culture. The cDNAs were prepared by reverse transcription and amplified for IL-2, -4, -5, -6 and -10 and IFN-γ by polymerase chain reaction.
All the cytokine mRNAs were detected in the Hashimoto's thyroid glands in large quantities. Six of the 12 Graves' disease thyroid glands showed, when compared with controls, an increased accumulation of transcripts for: IFN-γ, IL-2, -4 and -10 or IL-2, -4 and IFN-γ or IL-2 and IFN-γ or IFN-γ alone, each in one case or IL-2 alone in two cases. These cytokine profiles were not representative of a Th1 or Th2 phenotype. Increased amounts of cytokine mRNA in thyroid glands from Graves' disease patients were mostly associated with high microsomal antibody titres and/or prominent intrathyroidal lymphocytic infiltration. IL-6 and/or IL-10 mRNAs were detectable in all Graves' disease thyroid glands and in control thyroid tissue. IL-10 mRNA was not detectable in normal human thyroid epithelial cells in primary culture.
Graves' disease and Hashimoto's thyroiditis clearly differ with respect to the number of positive intrathyroidal cytokine mRNAs and their levels. The different cytokine patterns in Graves' disease and in Hashimoto's thyroiditis could reflect the clinical spectrum of autoimmune thyroiditis which is characterized by thyroid tissue destruction and/or thyroid autoantibody production. These data suggest that the course of autoimmune thyroiditis is regulated by the interplay of several cytokines.
Journal of Endocrinology (1994) 141, 309–315
Functional expression of the recombinant human FSH receptor
Authors: Minegishi T , Igarashi S , Nakamura K , Nakamura M , Tano M , Shinozaki H , Miyamoto K , Ibuki Y 
Published: December 2008

Abstract
The functional capacity of the recombinant human FSH (hFSH) receptor was tested on the basis of gonadotrophin stimulation of cyclic AMP (cAMP) production by transient transfections of 293 cells and stable transfections of Chinese hamster ovary (CHO) cells. A CHO cell line expressed with the hFSH receptor cDNA covering the entire amino acid coding region revealed the presence of FSH binding site (Kd 6·2 × 10−10 m) on the plasma membrane. Treatment of transfected cells with hFSH induced dose-dependent increases in intracellular cAMP production. These results indicate that the hFSH receptor functionally couples with endogenous adenylyl cyclase. Although rat FSH also induced dose-dependent increases in cAMP production, bovine FSH was effective only at high doses and human chorionic gonadotropin did not alter cAMP levels compared with control values.
Northern blot analysis with a cRNA probe derived from hFSH receptor cDNA indicated the presence of two common FSH receptor mRNA transcripts (2·4 and 4·1 kb) in RNA prepared from a human ovary and transfected cell lines.
Preincubation of CHO cells expressing a functional hFSH receptor (CHO-FSHR) with FSH for 16 h decreased the subsequent cAMP production resulting from a 30-min pulse of FSH stimulation. These results indicate that desensitization of the adenylyl cyclase response to FSH stimulation occurs in CHO-FSHR cells. This cell line therefore provides a tool with which to pursue detailed studies on the molecular basis of FSH-induced desensitization.
Journal of Endocrinology (1994) 141, 369–375
Insulin-like growth factor-binding protein-3 expression and secretion by cultures of human prostate epithelial cells and stromal fibroblasts
Authors: Birnbaum R S , Ware J L , Plymate S R 
Published: December 2008

Abstract
Prostate-specific antigen (PSA) was recently shown to be an insulin-like growth factor-binding protein (IGFBP)-3 protease. However, only IGFBPs-2 and -4 have been identified in conditioned medium of prostate epithelial cells. Using cultures of human prostate epithelial and stromal fibroblastic cells, we examined conditioned medium and cell extracts for evidence of IGFBP-3 expression and secretion. Western ligand blotting of conditioned medium from epithelial or stromal cultures revealed the presence of IGFBPs in the molecular weight range 36–48 kDa, suggestive of IGFBP-3. Western immunoblots of these media confirmed the presence of IGFBP-3. Northern analyses of extracts of both stromal and epithelial cells showed a 2·5 kb band, the size of IGFBP-3 mRNA. We conclude that prostate cells express IGFBP-3 and that local proteolysis by PSA could modify this binding protein's actions in the prostate.
Journal of Endocrinology (1994) 141, 535–540
Negative correlation between plasma GHRH values and growth velocity in short prepubertal children
Authors: Evain-Brion D , Porquet D , Fjellestad-Paulsen A , Donnadieu M , Noel M , Leger J , Simon D , Czernichow P 
Published: December 2008

Abstract
Numerous data suggest that impaired growth hormone secretion in short children is usually related to abnormal regulation of the hormone at the hypothalamic level. In order to improve our understanding of neurohypothalamic dysfunction in short children, we measured basal and peak (after l–dopa stimulation) plasma growth hormone-releasing hormone levels in 43 prepubertal children. Among them, in 23 children suspected of having hypothalamic growth hormone dysregulation, growth hormone-releasing hormone values were significantly higher than those observed in normal short stature children (n=20), no longer correlated with peak growth hormone following l–dopa, and negatively correlated with growth velocity. This suggests that a predominant inhibitor of growth hormone secretion, such as an increase in somatostatin tone, might be prevalent in a large number of children with partial growth hormone deficiency and suspected hypothalamic growth hormone dysregulation.
Journal of Endocrinology (1994) 141, 541–546
Binding of 1,25-dihydroxyvitamin D3 receptors to the 5′-flanking region of the bovine parathyroid hormone gene
Authors: Hawa N S , O'Riordan J L H , Farrow S M 
Published: December 2008

Abstract
To further define the binding site for receptors for 1,25(OH)2D3 (VDR) in the bovine PTH gene and to study the interactions of transcription factors with VDR, Southwestern and gel shift assays were used. Data from the former indicated binding of VDR to DNA fragments spanning the regions −451 to −348 bp and −668 to −452 bp. Studies using gel shift assays confirmed binding to the −451 to −348 bp fragment and specificity was shown by using excess concentrations of unlabelled −451 to −348 bp fragment to compete for binding, whereas excess unlabelled −347 to +50 bp did not compete. Binding was also observed with the −668 to −452 bp fragment but excess concentrations of unlabelled −668 to −452 or −451 to −348 bp fragments did not compete for binding to radiolabelled fragments. These data indicate the presence of two binding domains within this region; the upstream element having a lower affinity for VDR than the downstream element. In addition, there was no interaction between VDR and consensus sequences for AP1, AP2, AP3 and SP1. The putative vitamin D3 response element (VDRE) contains two similar hexameric steroid response element-like half-sites placed as AGGTCA-related direct repeats. The upstream repeat is at −461 to −456 bp and the downstream element is at −449 to −444 bp. The presence of these half-sites is consistent with our experimental data in which cleavage with SspI at −452 bp resulted in two DNA fragments which bound VDR.
Journal of Endocrinology (1994) 142, 53–60
Intermittent retinoie acid in combination with continuous oestradiol-17β increases cancellous bone volume in osteopaenic ovariectomized rats
Authors: Tobias J H , Gallagher A , Chambers T J 
Published: December 2008

Abstract
Although short-term administration of oestradiol-17β (OE2) stimulates cancellous bone formation in the rat, this is replaced by a tendency to suppression after prolonged treatment. Hence, in rats rendered osteopaenic by ovariectomy, OE2 administration fails either to induce a sustained increase in bone formation or to restore bone volume. A possible explanation for this failure is that OE2 also inhibits bone resorption, secondarily suppressing bone formation through coupling mechanisms. We therefore investigated whether the effects of OE2 treatment might be modified by intermittently stimulating bone resorption with retinoic acid (120mg/kg daily) for 4 out of every 20 days. We found, in a preliminary experiment using intact animals, that intermittent retinoic acid reduced cancellous bone volume, consistent with previously documented stimulation of bone resorption by retinoic acid. Rats were then rendered osteopaenic by ovariectomy, and given vehicle, retinoic acid and/or OE2. We found that animals treated with intermittent retinoic acid and OE2 showed a substantial increase in cancellous bone volume compared with ovariectomized animals treated with vehicle, retinoic acid alone or OE2 alone. Therefore, intermittent retinoic acid appears to cause a net increase in bone formation over resorption when given to ovariectomized animals in conjunction with OE2. We conclude that the effects of OE2 on cancellous bone are modified by intermittent treatment with retinoic acid, resulting in a substantial increase in bone volume.
Journal of Endocrinology (1994) 142, 61–67
The effects of pyroglutamylglutamylprolineamide, a peptide related to thyrotrophin-releasing hormone, on rat anterior pituitary cells in culture
Authors: Ashworth R J , Ham J , Cockle S M 
Published: December 2008

Abstract
Pyroglutamylglutamylprolineamide, which was first discovered in mammalian prostate, differs from thyrotrophin-releasing hormone (TRH) by substitution of glutamic acid for histidine at position two of the tripeptide. Recently, the newly discovered peptide has been identified in substantial concentrations in the rat anterior pituitary gland and, in this study, we have investigated the effects of the peptide on rat anterior pituitary cells in culture. GH3 cells were chosen to examine the possible effects of the new peptide, particularly in relation to its effects on the TRH receptor. This cell-type was deficient, in comparison with normal rat pituitary cells, in the new TRH-related peptide and appeared to be an ideal model cell in which to study the effects of pGlu-Glu-ProNH2. TRH (0·01–100 nm) was found to stimulate the secretion of both GH and prolactin from GH3 cells whereas pGlu-Glu-ProNH2 had no effect within the same concentration ranges. In contrast, at micromolar concentrations pGlu-Glu-ProNH2 exhibited intrinsic TRH-like activity causing stimulation of both GH and prolactin release from GH3 cells. Both TRH and pGlu-Glu-ProNH2 appeared to act through the same intracellular signalling mechanism, causing significant increases in intracellular inositol phosphate within the expected concentration ranges. However, pGlu-Glu-ProNH2 (up to 1 mm) displaced neither [3H]TRH nor [3H]MeTRH from membrane-binding sites on GH3 cells, suggesting that the effects of the new peptide were mediated through a second receptor. The physiological relevance of these effects of pGlu-Glu-ProNH2 requires further investigation.
Journal of Endocrinology (1994) 142, 111–118
The rate of cancellous bone formation falls immediately after ovariectomy in the rat
Authors: Lean J M , Chow J W M , Chambers T J 
Published: December 2008

Abstract
We have recently found that administration of oestradiol-17β (OE2) to rats stimulates trabecular bone formation. It is not known, however, whether oestrogen has a similar action on bone formation rate under physiological circumstances. Oestrogen is known to suppress bone resorption, and oestrogen-deficient states in the rat, as in humans, are associated with an increase in bone resorption that entrains an increase in bone formation. To see if the latter masks a relative reduction in bone formation, due to oestrogen deficiency, we measured bone formation very early after ovariectomy, before the resorption-induced increase in bone formation becomes established. To do this, rats were administered fluorochrome labels before and after ovariectomy, spaced at weekly intervals in the first, and 3-day intervals in the second experiment.
In both experiments there was a decrease in indices of bone formation in the labelling interval immediately following ovariectomy such that, using the shorter fluorochrome intervals, the mineral apposition rate fell to 69%, the double-labelled surface to 45%, and the bone formation rate to 36% of sham-ovariectomized levels. The reduction was not sustained in the subsequent label intervals, presumably masked by the increase in bone formation attributable to increased resorption. These results suggest that if bone formation is assessed before this resorption-entrained increase in bone formation occurs, oestrogen deficiency is associated with a reduction in dynamic indices of bone formation. Thus, these experiments suggest that oestrogen stimulates bone formation under physiological circumstances, and that the osteopaenia that follows oestrogen deficiency may be attributable not only to an increase in bone resorption, but also to a relative deficiency in bone formation.
Journal of Endocrinology (1994) 142, 119–125
Human chorionic gonadotrophin: a chemoattractant for human blood monocytes, neutrophils and lymphocytes
Authors: Reinisch N , Sitte B A , Kähler C M , Wiedermann C J 
Published: December 2008

Abstract
Treatment of rats with human chorionic gonadotrophin (hCG) induced in the testes an inflammation-like reaction characterized by migration of leukocytes into the interstitial space. In order to find out whether hCG acts in a direct manner in this process, we tested peripheral human blood leukocyte attraction by hCG in vitro. Chemotaxis through cellulose nitrate to gradients of test substances was measured using a 48-well microchemotaxis chamber. Human CG was found to be a potent attractor of neutrophils, monocytes and lymphocytes in vitro in the picomolar concentration range. Checkerboard analyses revealed that the type of migration depends on positive concentration gradients of hCG. The chemoattractant nature of hCG is consistent with its having a role to play in regulation of tissue accumulation of these cells within the reproductive tract.
Journal of Endocrinology (1994) 142, 167–170