bluuebunny/crossref_metadata_2025 huggingface dataset:
EFFECT OF EXERCISE ON THYROID PARAMETERS AND ON METABOLIC CLEARANCE RATE OF ANTIPYRINE IN MAN
Authors: Theilade Peter , Hansen Jens Mølholm , Skovsted Lis , Kampmann Jens P.
Published: December 2008

Serum concentrations of thyroxine, triiodothyronine, free-thyroxine-index, free-triiodothyronine-index and reverse-triiodothyronine (r-T3) were followed in nine normal men, aged 18 to 22 years, during a nights rest and during nine hours march (4.6 km/h). In addition antipyrine elimination was measured in the same periods after iv injection of 1 gram of antipyrine. No significant differences were found in any of the thyroid parameters during exercise except for a small increase in serum r-T3 after 3 hours. During rest a small but significant decrease was found in serum r-T3. Otherwise no significant differences were found except for a significant increase in free-T3-index after 3 hours rest.

The mean value of total body clearance of antipyrine was identical at rest and during exercise.

In conclusion: Prolonged exercise does not change the metabolic clearance rate of antipyrine and does not elicit any major change in the serum concentrations of the thyroid hormones.
INHIBITORY EFFECT OF CERTAIN DRUGS ON THYROID HORMONE BINDING BY HUMAN LIVER CYTOSOL
Authors: Hamada Satoshi , Nishimoto Miyuki
Published: December 2008

Effects of dinitrophenol (DNP), salicylate, diphenylhydantoin (DPH) and heparin on thyroid-hormone binding by human liver cytosol were studied using Pevikon thin-layer electrophoresis. Thyroxine (T4) binding by the major cytosol T4-binding protein, hT4-2, was significantly depressed with these drugs, and the displaced T4 was bound by another cytosol binding protein, hT4-1. Triiodothyronine (T3) binding by the major cytosol T3-binding protein, hT3-2, was significantly decreased with DPH and heparin, but not with DNP and salicylate. Comparative studies using human serum indicated that T4 binding by serum Ti-binding prealbumin (TBPA) was inhibited with DNP and salicylate, and that binding of T4 and T3 by serum T4-binding globulin (TBG) was decreased only with DPH. The results obtained indicate that these drugs inhibit thyroid-hormone binding by the liver cytosol binding proteins for T4 and T3, and that the displaced hormones may be responsible for changes in free hormone levels in serum, and within the cells, and for the accelerated turnover of hormones.
IODOAMINO ACID SYNTHESIS IN THYROID LOBES IN VITRO WITH EXCELLENT YIELD OF IODOTHYRONINES
Authors: Okamura Ken , Inoue Kenjiro , Nakashima Toshiro , Shiroozu Akiyo , Yoshinari Mototaka
Published: December 2008

Thyroid lobes of male Sprague-Dawley rats on an iodine-sufficient diet were incubated in our improved in vitro system with 0.01 μm 127I and 5 mU/ml of bovine TSH. Thyroidal 131I-uptake and the relative incorporation of iodine into iodothyronines increased with time. The average yield of each iodoamino acid after 8 h of incubation was: monoiodotyrosine 28.0 %, diiodotyrosine 46.5 %, triiodothyronine 1.9 % and thyroxine 13.9 %, which showed a striking resemblance to the values obtained in vivo. The yields of iodotyrosines and iodothyronines, the latter in particular, were strikingly high, and this system is considered to be useful in the study of thyroidal iodine metabolism.

Effects of TSH, temperature and pH of the medium were examined and a unique effect of pH was observed on the iodoamino acid synthesis. As the pH was elevated from 6.8 to 7.9, 131I-uptake, MIT/DIT ratio, T4/DIT ratio and T3/T4 ratio increased. The effect of slightly alkaline pH was considered to be similar to that observed in iodine-deficiency.

It was found that the rubber stoppers which are commonly used in shortterm incubation contain a kind of potent inhibitor of thyroid hormone synthesis. The pattern of inhibition was similar to that of thionamide compounds.
REGULATORY HYPERPARATHYROIDISM IN A PIG BREED WITH VITAMIN D DEPENDENCY RICKETS
Authors: Wilke R. , Harmeyer J. , von Grabe C. , Hehrmann R. , Hesch R. D.
Published: December 2008

A radioimmunoassay for porcine parathyroid hormone has been developed and applied to measure immunoreactive parathyroid hormone (PTH) in plasma of pigs with hereditary vitamin D dependency rickets (VDDR) (pseudovitamin D deficiency rickets). Levels of 25-hydroxycholecalciferol (25-(OH)-D3) in plasma were measured by a protein binding assay. Both plasma concentrations of PTH and 25-(OH)-D3 showed an approximately 4-fold increase compared to normal pigs. PTH levels increased with duration of the disease. Daily dosing of the animals with 1–4 μg of 1,25-dihydroxycholecalciferol (1,25-(OH)2-D3) reduced PTH concentrations and resulted in clinical healing. Iv administration of 10 μg of 25-(OH)-D3/day did not alter PTH concentrations nor the clinical symptoms. The results suggest that these animals suffer from regulatory hyperparathyroidism. The metabolic defect could be due to a failure of the kidney to convert 25-(OH)-D3 to 1,25-(OH)2-D3.
EFFECT OF A SEQUENTIAL OESTROGEN-PROGESTIN THERAPY ON THE PLASMA LEVEL OF OESTROGENS AND LIPIDS IN POST-MENOPAUSAL WOMEN
Authors: Lillienberg L. , Adlercreutz H. , Svanborg A.
Published: December 2008

With the aim of minimizing side effects of substitution therapy a natural synthetic oestrogen, oestrone sulphate, and norethisterone acetate were administered to 6 oophorectomized women and 4 women with physiological menopause cyclically in order to follow the pattern of physiological variations during the menstrual cycle as closely as possible, without causing bleedings. In addition to assessing the clinical effects and analyses of plasma oestrone and oestradiol-17β, the metabolic effects on plasma triglycerides, cholesterol and individual phospholipid levels, as well as on the fatty acid composition of lecithin were followed.

The oral administration of oestrone sulphate in doses varying with the "cycle" from 0.5 to 1.5 mg/day gave in these women plasma concentrations of oestrone in the lower pre-menopausal physiological range causing cyclic variations in plasma lipids similar to those during a physiological menstrual cycle but did not normalize the plasma oestradiol concentrations and did not give acceptable therapeutic effect. Total phospholipids, total and free cholesterol, triglycerides and the percentage of lecithin were higher, and the percentage of lysolecithin lower in the oestrogen phase, than in the progestin phase. The changes in linoleic acid in lecithin varied inversely with changes in arachidonic acid in lecithin and cyclic variations also occurred in the content of palmitic and stearic acid in lecithin.

When previous treatment with ethinyloestradiol was exchanged with oestrone sulphate the total cholesterol values in plasma varied in the opposite direction. The results obtained in this and previous studies suggest different effects of ethinyloestradiol and oestrone (oestrone sulphate?) in the metabolism of certain sterols, and that the effect of oestrone (or oestrone sulphate?) on plasma cholesterol dominates during physiological condition in the follicular phase of the menstrual cycle.
HCS REGULATION IN CULTURED PLACENTA: ACTION OF GLUCOSE
Authors: Belleville F. , Lasbennes A. , Nabet P. , Paysant P.
Published: December 2008

The regulation of HCS secretion on placenta cultures in the presence of [3H] leucine was studied.

When Eagle's medium containing 0.0055 m of glucose per liter is used, it it noted that the HCS increases regularly in the culture medium, whereas it diminishes in the explants. [3H] HCS represents about 50 % of the [3H] proteins, and among these proteins HCS is preferentially secreted in the culture medium.

The absence of glucose in the medium provokes a decrease in all of the cellular metabolism as well as a decrease in protein and HCS secretions, with an accumulation of preformed HCS in the tissues.

An increase in the glucose level in the medium 0.011 and 0.027 m provokes a selective decrease of HCS secretion with an accumulation of preformed HCS in the tissues, determining a long term decrease in HCS synthesis. Insulin added in the mediums (60 μU/ml) does not change the results significantly.

The use of structural analogues of the glucose shows that the point of impact of the HCS secretion regulation by the glucose is membranous; however, it seems that at a second stage one or some glucose metabolites also intervene.

There is no self regulation of HCS secretion in vitro.
LONG-TERM EFFECTS OF HUMAN GROWTH HORMONE ON PLASMA AMINO ACIDS TRANSPORT IN HYPOPITUITARY DWARFISM
Authors: Sato Tamotu , Uchigata Yasuko
Published: December 2008

The chronic effects of human growth hormone (hGH) on the transport of plasma amino acids (PAA) induced by glucose administration were studied in 17 patients with GH deficiency at different stages in the course of GH therapy. The study comprised 9 patients before and after 2–3 months of the therapy and 8 patients after prolonged treatment of 2–3 years. Five normal children served as controls. Analysis of 13 neutral and acidic PAA concentrations before and 2 h after glucose loading was carried out, and a decrease in PAA was expressed as a percentage of 2 h value to the initial level (PAA ratio). Fasting levels of several PAA before treatment were significantly lower than those of controls which gradually rose during the course of the therapy. The mean ± sd value of PAA ratio was also reduced before treatment (68 ± 16 %) vs. that of controls (82 ± 16 %, P < 0.05), which rose after 2–3 months of GH therapy to a comparable level of controls (91 ± 26 %). In patients treated for 2–3 years, however, PAA ratio was decreased to the level of pre-treatment (57 ± 17 %), P < 0.01 vs. control). These changes were pronounced in glucogenic, branched-chain and aromatic amino acids. Serum gamma-glutamyltranspeptidase (GGTP) activity was also low before GH therapy and normalized by the treatment. However, no significant correlation was noted between PAA ratio and serum GGTP activity or GH level. These results indicate that PAA transport evoked by endogenous insulin changes considerably according to the duration of GH therapy, and this may reflect a peripheral alteration of responsiveness to exogenous GH in the prolonged course of GH therapy in pituitary dwarfs.
THE EFFECT OF PREGNANCY AND LACTATION ON PITUITARY PROLACTIN-SECRETING TUMOURS
Authors: Zárate Arturo , Canales Elias S. , Alger Mucia , Forsbach Gerardo
Published: December 2008

Management of the amenorrhoea-galactorrhoea syndrome due to pituitary tumour is still controversial. However, in cases of pituitary prolactinproducing adenomas, ovulation and pregnancy are readily induced medically with bromocriptine. In our series of 14 patients conception occurred in all cases within 6 months of treatment. All of the 14 women had uneventful full term pregnancies and normal infants. Neither neurological nor visual symptoms appeared in these patients during their pregnancies. Lactation had no apparent effect on the growth of the pituitary tumour since radiological and neurological evaluations were unchanged. Prolactin levels for each patient following the termination of pregnancy and breast feeding were apparently diminished or similar to the prolactin levels obtained prior to treatment. This finding could add to the evidence that probably there was no further growth of the pituitary tumour. Three of the 14 women have had a second pregnancy without any complications. It is recommended that patients with microadenomas can be allowed to become pregnant on bromocriptine alone, provided that they are carefully supervised during pregnancy.
FORMATION OF ANTIBODIES TO SYNTHETIC HUMAN CALCITONIN DURING TREATMENT OF PAGET'S DISEASE
Authors: Dietrich F. M. , Fischer J. A. , Bijvoet O. L. M.
Published: December 2008

Low-titre antibodies to synthetic human calcitonin (hCT) were detected in a 69-year-old woman suffering from Paget's disease who was treated for 16 months with hCT and the diphosphonate EHDP. Levels of antibody were highest between 10 and 18 months after commencement of therapy, slowly decreased after completion of treatment and were later no longer measurable. There was no immunological response to a single re-injection of hCT 14 months after discontinuation of therapy. Formation of antibodies to hCT in man is a very rare event, this being the first recorded case of an immune response to synthetic human calcitonin, whereas synthetic salmon calcitonin induces an immune response in a high percentage (up to 78 %) of the patients treated with this hormone.
TSH SYNTHESIS AND RELEASE IN THE THYROIDECTOMIZED RAT:
Authors: Spira O. , Birkenfeld A. , Gross J. , Gordon A.
Published: December 2008

Groups of surgically thyroidectomized (T) male rats were sacrificed at intervals during the period of 1 to 5 and 30 to 180 days after  Plasma T3, T4 and TSH levels and pituitary TSH content were measured by RIA. A drop of plasma T3 and T4 from normal to undetectable values occurred by day 3 post . There was a progressive increase of plasma TSH from the normal value of 136 ± 14 ng/ml to 1623 ± 186 ng/ml (mean ± sem) at day 5 post T, reaching at 30 days a new plateau of 8618 ± 527 ng/ml. These levels remained unchanged up to 130 days post . At 180 days, plasma TSH (4123 ± 991 ng/ml) fell significantly below the plateau level. Pituitary TSH content fell from the normal value of 80.9 ± 15.9 μg/mg to a nadir of 12.7 ± 1.4 μg/mg at day 4 post  and then slowly rose to 98.6 ± 5.9 μg/mg at 100 days, remaining at this level for another 30 days and finally declining significantly at 180 days post .

The rates of TSH release and synthesis were calculated using the metabolic clearance rates (MCR), determined from the curves of disappearance of injected [125I]-TSH by a non-compartmental analysis. The MCR values decreased, starting at 8 days after T, and reached about half the normal value from 30 days onwards (0.257 ± 0.03 to 0.144 ± 0.001 ml/min/100 g b.w.).

The rate of TSH release was increased as early as the first day post . A 6-fold increase was reached after 5 days and a new steady state of about 32-fold increase was attained within 1 month. TSH synthesis was also stimulated. However, it lagged behind the stimulation of the release for the first 4 days after .

The data indicate that: a) The depletion of thyroid hormones affects both synthesis and release of TSH. b) Under prolonged hypothyroidism TSH release and synthesis are in equilibrium, at a markedly enhanced rate. c) Very severe and prolonged hypothyroidism results in a decline in both pituitary and plasma TSH levels.
TSH SYNTHESIS AND RELEASE IN THE THYROIDECTOMIZED RAT:
Authors: Spira O. , Birkenfeld A. , Avni A. , Gross J. , Gordon A.
Published: December 2008

The time and dose dependent effects of T3 on the anterior pituitary (AP) TSH release and synthesis were studied in rats 5 days after thyroidectomy (-5d). T3, in various doses, was injected iv to animals which were killed at various times later. Plasma and AP TSH were measured. T3 lowered plasma TSH to a minimum within 3 h. An inverse linear relationship was found between T3, up to 634 ± 134 ng/100 g b.w. (mean ± sd) and plasma TSH. Higher doses of T3 did not lower plasma TSH any further. At T3 of 634 ± 134 ng/100 g b.w. the specific AP binder was calculated to be 68 % to 90 % saturated; thus suggesting a relationship between occupancy by T3 of the AP binder and the regulation of TSH release.

The TSH release and synthesis rates were compared after 0.5 μg, 1 μg and 25 μg T3. All three doses of T3 suppressed the release as well as the synthesis. The effect of T3 on the synthesis rate, however, lagged behind the effect on the release both in time and magnitude.
CORRELATION OF PLASMA NON-CONJUGATED OESTRIOL AND PLASMA CORTISOL IN LATE HUMAN PREGNANCY
Authors: Reck G. , Renner A. , Sinns G. , Breckwoldt M.
Published: December 2008

The present study concerns the diurnal variations of free plasma oestriol and their relationship to maternal plasma cortisol in late human pregnancy. Four pregnant women volunteered for the study. According to the half-life time of oestriol blood was drawn at intervals of 30 and 60 minutes, respectively, over a period of 24 hours.

Free oestriol was measured by radioimmunoassay and cortisol was quantitated by a protein binding method.

All patients exhibited a circadian rhytm for free oestriol with higher values in the evening and early night (14.4 ± 3.7 ng/ml) than in the morning (11.3 ± 2.3 ng/ml, P < 0.001). The course of oestriol followed plasma cortisol in a significant negative correlation (r = −0.566, P < 0.001). During the period of low cortisol concentration oestriol levels demonstrated the phenomenon of episodic secretion.

The results suggest that the maternal adrenals predominantly regulate the circadian rhythm of free oestriol by a negative feed-back action on the foetal hypothalamus.
ANOVULATION AND OVIDUCTAL HYPERPLASIA IN RATS TREATED WITH CLOMIPHENE CITRATE 5 DAYS AFTER BIRTH
Authors: Morishita Hajime , Nakago Kichijiro , Ii Kunio , Hashimoto Tadashi , Kawamoto Masaru , Tanaka Toshiro , Higuchi Kazuhiko , Miyauchi Yasuyo , Ozasa Teruyasu
Published: December 2008

Five day old female rats were administered either 500 μg clomiphene citrate or propylene glycol. Vaginal opening occurred significantly earlier in the clomiphene treated group as compared with the control group. Clomiphene treated rats showed permanent sterility associated with anovulatory vaginal cycles in which the stage of vaginal cornification predominated. Furthermore, clomiphene treated rats exhibited a high incidence of pyosalpinx (or oviductal abscess). The possible mechanisms responsible for the anovulatory sterility and the pyosalpinx induced by neonatal clomiphene treatment are discussed.
INFLUENCE OF THE PURITY OF THE IODINATED TRACER ON THE SPECIFICITY OF THE RADIOIMMUNOASSAY OF HUMAN FOLLICLE-STIMULATING HORMONE
Authors: Marana R. , Suginami H. , Robertson D. M. , Diczfalusy E.
Published: December 2008

The objective of this study was to establish whether [125I]hFSH subunits are formed during iodination of hFSH by a mild (lactoperoxidase) technique, and if so which fractionation procedure provides the best separation of [125I]hFSH from its subunits. In addition, the effect of the 125I subunits on the specificity of the hFSH radioimmunoassay technique was examined. The products of iodination of hFSH were fractionated by a number of techniques consisting of low and high resolution gel filtration procedures and adsorption on either cellulose or Concanavalin A coupled to Sepharose. The efficacy of the adsorption methods was assessed by a subsequent high resolution gel filtration procedure (Ultrogel AcA 54). Radioreceptor and radioimmunoassay methods were used to monitor the profiles of hFSH, hFSHα and hFSHβ subunits and to assess the recoveries of radioreceptor-active hFSH obtained by the different procedures.

Iodination of a highly purified hFSH preparation invariably resulted in the formation of both [125I]hFSH and [125I]hFSH subunits. The proportion of radioactivity associated with the 125I subunit peak to that of the [125I]hFSH peak was 10 % when the iodination products after low resolution gel filtration were fractionated by a high resolution gel filtration procedure. The corresponding amount of subunits obtained by adsorption on cellulose and Concanavalin A was 71 % and 6 %, respectively. Thus in comparison with low resolution gel filtration there was a partial separation of [125I]hFSH from [125I]hFSH subunits on Concanavalin A while no separation was effected on cellulose. In fact, the results suggest that 125I subunits were formed during fractionation on cellulose. The recoveries of hFSH activity following fractionation on cellulose and Concanavalin A were significantly lower (27 % and 65 %) than those obtained by either low or high resolution gel filtration techniques. A marked reduction in the specificity of the RIA of hFSH was found when [125I]hFSH subunits rather than [125I] hFSH were used as tracer in the assay.

It is concluded that the presence of 125I subunits in [125I]hFSH preparations used as tracer in the RIA of hFSH can diminish the specificity of the assay. The routine employment of a high resolution gel filtration procedure which provides a complete separation of 125I subunits from the intact hormone, is suitable for the elimination of this source of assay invalidity while the other fractionation procedures tested (cellulose adsorption or Concanavalin A) are not.
THE ASSAY OF HUMAN FOLLICLE-STIMULATING HORMONE PREPARATIONS: THE CHOICE OF A SUITABLE STANDARD
Authors: Marana R. , Robertson D. M. , Suginami H. , Diczfalusy E.
Published: December 2008

Eleven pituitary or urinary preparations of varying purity were assayed for FSH activity by an in vitro bioassay method, a receptor binding assay (RBA) technique and a radioimmunoassay (RIA) procedure, employing two anti-FSH sera with and without absorption with hCG. All methods were specific for hFSH, since other glycoproteins (hFSHα and hFSHβ subunits, hLH, hCG and hTSH) elicited little, if any, response. A partially purified hFSH preparation (1st IRP of Human Pituitary Gonadotrophins (FSH and LH/ICSH) for bioassay, code No. 69/104) was used as standard in all assays. In addition, potency estimates were expressed in terms of a highly purified hFSH preparation (hFSH-Kabi, Lot No. 19344) and in terms of the hMG (2nd IRP).

Significant differences in the ratios of biological activity to receptor binding activity (B/R) and to immunological reactivity (B/I) were observed between preparations which were unrelated to their level of purity. The use of the 69/104 preparation as standard gave significantly higher B/R and B/I ratios than the use of the hMG (2nd IRP) and of a highly purified hFSH preparation. In addition, the use of the hMG (2nd IRP) as a standard gave significantly higher B/R ratios than that of the highly purified hFSH preparation.

These results indicate that the 69/104 and hMG (2nd IRP) preparations contain significantly more biologically inactive receptor binding material than the more extensively purified hFSH preparation. Furthermore, the 69/104 preparation contains significantly more biologically inactive immunologically reactive material than both hMG reference standards and the highly purified hFSH preparation.

It is concluded that, because of the presence in the 69/104 preparation of relatively large quantities of biologically inactive material which behaves in both the receptor binding assay (RBA) and radioimmunoassay (RIA) procedures as hFSH, this preparation is unsuitable as standard for the quantitation of FSH activity by methods other than bioassays. For the same reason, the relatively crude 2nd IRP (but not its replacement, the 1st IS for human urinary FSH and LH for bioassay) appears to be unsuitable as a standard for the assay of hFSH by RBA procedures. Among the limited number of preparations studied, a highly purified pituitary hFSH preparation appears to be the most satisfactory as a provisional standard for hFSH assays, although even this material contains some biologically inactive hFSH-like material.
BIOLOGICALLY ACTIVE LUTEINIZING HORMONE (LH) IN PLASMA
Authors: Robertson D. M. , Puri Vipla , Lindberg Monica , Diczfalusy E.
Published: December 2008

The relationship between the biological and immunological activities of human luteinizing hormone (hLH) in plasma collected from female subjects was examined. The biological activity was measured by an in vitro bioassay and the immunological activity by an hLH radioimmunoassay (RIA), using improved reagents, such as the 1st IRP for human pituitary LH for immunoassay (code No. 68/40) as standard, a subunit-free biologically active iodinated hLH preparation as tracer and an anti-hLH serum of relatively high specificity.

Similar profiles of biological (B) and immunological (I) activity were obtained in the plasma samples collected daily throughout 40 menstrual cycles (5 cycles from each of 8 subjects). However, the B/I ratios were significantly lower during the period of LH surge (P < 0.001) than throughout the remainder of the cycle.

The within- and between-assay variation in B/I ratios was investigated by the simultaneous assay of biological and immunological activities in plasma pools obtained by combining equal aliquots of plasma from each daily sample of the menstrual cycle from each of 5 cycles of each of 4 subjects. The analysis of these 20 pools revealed highly significant individual differences in B/I ratios, ranging from 0.81 to 1.33. The coefficient of variation was 20 % between-subjects and 5 % within-subjects. There was no seasonal variation in B/I ratios. That the individual differences in plasma B/I ratios were not attributable to the procedure of pooling was ascertained by the simultaneous assay of both activities in parellel in daily plasma samples and in the pools formed from these samples from three complete cycles.

Thus the analysis of the differences in B/I ratios obtained throughout the menstrual cycle revealed three major sources of variation. The first occurs in the form of generally elevated (higher than unity) B/I ratios, the second consists of a significant drop in B/I ratios during the midcycle LH surge, and the third source is represented by the significant between-subject differences.

It is concluded that the first source is attributable to the relatively higher levels of "impurity" (i.e. biologically inactive, immunologically active material) in the standard preparation compared to those present in plasma, whereas the other sources are due most probably to the presence in plasma of biologically inactive, immunologically active material of unknown composition and origin. If so, the latter source limits the quantitative significance of the RIA procedures employed. It is suggested that these three sources of variation account for most of the differences in B/I ratios for plasma hLH reported in the literature.
DIFFERENCES IN THE BLOOD GLUCOSE RESPONSE OF MICE TO ALLOXAN AND ALLOXAN-INHIBITING COMPOUNDS
Authors: Boquist L.
Published: December 2008

A typical triphasic blood glucose response (response A) is seen in fed and starved mice treated with alloxan alone, whereas a marked initial hyperglycaemia (to which alloxan probably has not contributed) and an abolished second hyperglycaemia (response B) are found in starved mice given D-glucose, D-fructose, D-mannose, and sodium lactate, and in fed mice treated with p-hydroxymercurigenzoate (PMB), D-mannoheptulose (MH) or diphenylhydantoin (DPH) before alloxan injection. An abolished initial hyperglycaemia, but a preserved "second" hyperglycaemia (response C), is observed in starved mice given PMB, MH or DPH before alloxan, indicating that an initial hyperglycaemia is not a prerequisite for B-cell damage and development of alloxan diabetes. Fed and starved mice pre-treated with NaHCO3, acetazolamide (AZM), L-leucine or tolbutamide exhibit neither any initial nor any second hyperglycaemia (response D) following alloxan injection.

The findings suggest that the inhibition of alloxan toxicity caused by pre-treatment with D- glucose, D-fructose, D-mannose, PMB, MH or DPH, and to some extent also sodium lactate, is dependent upon development of hyperglycaemia which may affect the B-cells secondarily and make them insensitive to alloxan, whereas these compounds are not antagonistic to alloxan in the absence of hyperglycaemia, e.g. when PMB, MH or DPH are given to starved mice. NaHCO3, AZM, L-leucine and tolbutamide seem to antagonize alloxan by other mechanism(s), probably through a direct action upon the B-cells.
INACTIVATION OF RENIN IN A MIXED MITOCHONDRIAL-LYSOSOMAL FRACTION OF POST-PARTUM UTERUS
Authors: Jørgensen Jørgen
Published: December 2008

The marked renin inactivation seen during in vitro incubation of post-partum uterine slices which mimics the in vivo condition, is not accompanied by a similar general proteolysis. The inactivating mechanism is so far non-specific with respect to organ or species as added hog renal renin is inactivated at a similar rate as endogenous renin. Endogenous alkaline phosphatase is not significantly inactivated and added alkaline phosphatase is completely stable.

A marked inactivation of endogenous renin also takes place during incubation of a mixed mitochondrial-lysosomal suspension prepared from post-partum uterus. The process is more pronounced at pH 7.4 than at 6.8. Freezing and thawing and addition of Triton X-100 prior to incubation inhibits the inactivation. ATP and α-ketoglutarate slightly stimulates the process while CoA and chloroquine have no effect. Both iodoacetate and phenylmethylsulphonylfluoride inhibit the inactivation, suggesting that more than one enzyme is involved in the inactivation.
CALCITONIN IN EXTRATHYROIDAL TISSUES OF MAN
Authors: Becker Kenneth L. , Snider Richard H. , Moore Charles F. , Monaghan Kathleen G. , Silva Omega L.
Published: December 2008

Prior studies have demonstrated detectable immunoreactive calcitonin in the serum and urine of totally thyroidectomized humans, suggesting that the hormone may be secreted by extrathyroidal tissues. Accordingly, a study of the immunoreactive calcitonin content of human tissues was undertaken, utilizing autopsy material from 23 patients. Significant amounts of calcitonin were found in many extrathyroidal tissues, ranging up to 40 ng/g wet weight. The hormone was detectable with two antibodies having different region specificities for calcitonin. Gel filtration and subsequent radioimmunoassay demonstrated that extrathyroidal tissue has calcitonin fractions of the same molecular size and charge characteristics as do the serum and thyroid. The finding of large amounts of extrathyroidal calcitonin may explain why thyroidectomy in man is not accompanied by marked changes in calcium metabolism.
Cholinergic inputs to the amygdala and the control of gonadotrophin release
Authors: Piva Flavio , Borrell José , Limonta Patrizia , Gavazzi Gilberto , Martini Luciano
Published: December 2008

Adult female rats castrated 4 weeks before were implanted bilaterally into the basomedial area of the amygdala with drugs known to mimic or to counteract the actions of acetylcholine. The animals were sacrificed at different time intervals after the implantation of the different compounds, and serum levels of LH and FSH were measured by radioimmunoasay. The data obtained indicate that the intra-amygdalar implantation of the muscarinic blocker atropine induces a significant increase of the release of LH without altering FSH secretion. The implantation of two cholinomimetic drugs, pilocarpine, an almost pure muscarinic agonist, and carbachol, which possesses both muscarinic and nicotinic properties, exerted an inhibitory effect only on LH release. On the contrary, the intra-amygdalar placement of the nicotinic blocker mecamylamine was followed by an increase of FSH with no changes in LH. These observations may suggest that cholinergic signals reaching the amygdala may be of some relevance in the mechanisms controlling gonadotrophin secretion. Muscarinic receptors seem to play an inhibitory role in the regulation of LH secretion, while nicotinic receptors seem to modulate in an inhibitory way FSH release.
Pseudohypoparathyroidism associated with hypercalcitoninaemia
Authors: Wägar Gustav , Lehtivuori Juhani , Salvén Ilkka , Backman Ralf , Sivula Arto
Published: December 2008

A case of a 33 year old man with type I of pseudohypoparathyroidism associated with hypercalci toninaemia and deficiency of prolactin and growth hormone is reported. The diagnosis of pseudohypoparathyroidism was made by recognition of the classic skeletal signs of Albright's osteodystrophy and confirmed by an infusion test with parathyroid hormone, which revealed a lack of both a cyclic AMP and phospaturic response. By investigation of the endocrine status the function of the pituitary/thyroid and pituitary/testis axes as well as the adrenal cortex was observed to be normal. The basal prolactin concentration was however, lower than normal and a lack of response in the growth hormone level in two glucagon tests was observed. Furthermore the basal calcitonin level was higher than normal and by provocation with pentagastrine the calcitonin secretion was very high despite an only slightly decreased serum calcium level. By operation the thyroid gland was normal and by light microscopy of a biopsy no signs of medullary carcinoma was observed. No good explanation for the high calcitonin basal level and secretion was found.
The concentration of 13,14-dihydro- 15-oxo-prostaglandin F2α in peripheral venous plasma throughout the normal ovarian and menstrual cycle
Authors: Koullapis E. N. , Collins W. P.
Published: December 2008

The concentration of 13,14-dihydro-15-oxoprostaglandin F2α (PGFM) has been measured in daily samples of peripheral venous plasma from 5 women throughout the ovarian or menstrual cycle. The values have been combined by days, relative to a pre-ovulatory peak, the LH peak and to Day 1 of the next menstrual cycle. The patterns (geometric means) have been related to the corresponding values for oestradiol, LH and progesterone.

The results show that there was considerable variation in the concentration of PGFM (50–909 pmol/l; n = 140) and that the coefficient of variation within an individual cycle ranged from 30–74%. Nevertheless two peaks one pre-ovulatory (associated with a marked increase in the level of circulating oestradiol) and one pre-menstrual (associated with rapidly falling levels of circulating oestradiol and progesterone) were apparent in all cycles. The concentration of PGFM during the pre-ovulatory rise was 521 ± 325 pmol/l; mean ± sd and the corresponding value for the pre-menstrual rise was 571 ± 325; both peaks were significantly higher (P < 0.0025, P < 0.0005, respectively, Student's t-test) than during the remainder of the cycle (257 ± 190). There was no significant difference, however, between the concentration during the follicular and luteal phases.
Uptake of T3 receptor complex by liver cell nuclei in vitro
Authors: DeGroot Leslie J. , Rue Paul A.
Published: December 2008

In order to study factors which might control the transport of the nuclear receptor for thyroid hormone from its extranuclear area of synthesis into the nucleoplasm, rat liver nuclei were incubated in vitro with nuclear triiodothyronine binding protein complex labelled with [125I]T3. Most experiments were conducted in 0.32 m sucrose + 1 mm MgCl2 + 2 mm CaCl2 + 10 mm Tris Cl, pH 7.4 buffer, + 1 mm dithiothreitol1. Uptake was rapid, even at 0°C, and under the conditions of incubation about 30% of the complex was bound to the nuclei. Washing gradually removed the complex. The complex could be recovered by extraction with 0.3 m KCl containing solutions. Uptake was related to volume of nuclei. It was inhibited by elevated KCl concentrations. Uptake of receptor-T3 complex was not inhibited by azide, cyanide, DNP, KI, or antithyroid drugs. Uptake of the [125I]T3 complex was much greater than 125I-labelled protein such as hLH, hFSH, hCG, or of free T3. Ovalbumin, haemoglobin, and bovine serum albumin did not compete with or inhibit uptake of the complex. There was no evidence of saturation of the binding sites for the complex in the nuclei. ATP, CTP, GTP, and UTP elevated uptake of the T3-receptor complex by nuclei when added an unphysiologically high concentration of 10−3m. The same concentrations of nucleotides inhibited binding of T3 to the receptor complex. When the studies described above were repeated with 0.12 m KCl in all solutions, the total uptake was less, but all phenomena were entirely reproduced.

This process may provide an analogue for the movement of NTBP into the nucleus. Whether the process studied in vitro actually represents a process of physiological importance, or one where metabolic controls are introduced, is as yet unknown.
Practical procedure for enzyme immunoassay of progesterone in bovine serum
Authors: Nakao Toshihiko
Published: December 2008

An enzyme immunoassay of progesterone was established by using β-galactosidase from E. coli as a label.

The enzyme was conjugated with 11α-hydroxyprogesterone-hemisuccinate using water-soluble carbodiimide. Rabbit antiserum to 11α-hydroxyprogesterone-hemisuccinate-bovine serum albumin was previously obtained and anti-rabbit gamma globulin goat serum was used as second antibody. The enzyme activity was measured by utilizing hydrolysis of O-nitrophenyl-β-D-galactopyranoside. The least detectable concentration of progesterone was 12 pg per tube. The measurable range of progesterone in 0.1 ml of bovine serum was between 0.25 ng/ml and 10 ng/ml.

This method satisfied the general criteria regarding specifity, precision and recovery rate. Correlation between the progesterone levels determined by enzyme immunoassay and radioimmunoassay was quite high (r = 0.99, P ≦ 0.01). The present enzyme immunoassay can be applied for practical and routine analysis of serum progesterone.
The effect of conception on the concentration of urinary oestrone-3-glucuronide, LH/hCG and pregnanediol-3α-glucuronide
Authors: Branch Christine M. , Collins Patricia O. , Kilpatrick M. J. , Collins W. P.
Published: December 2008

The concentrations of oestrone-3-glucuronide, LH/hCG and pregnanediol-3α-glucuronide have been measured in daily samples of early morning urine from 6 women throughout the normal ovarian cycle and from 5 subjects, who conceived during the period of study. In addition, the ratio of oestrone to pregnanediol glucuronide was calculate as an additional index of ovarian function.

The results showed that the ratio during the follicular phase of the cycle was similar in both groups of women. Moreover, there was no significant difference between the groups in either the duration or intensity of the LH peak. Seven days later, however, the women who conceived excreted significantly higher amounts of oestrone-3-glucuronide (P<0.05) and 12 days after the LH peak the values for pregnanediol-3α-glucuronide and LH/hCG were also elevated (P<0.05). A defined increment, in the concentration of hCG (3 times the mean basal level) occurred 11 to 15 days after the peak of LH and appeared 3 to 5 days after the increased excretion of the steroid glucuronides.
The effect of galactose oxidase treatment on the hepatic binding and biological activity of desialylated human chorionic gonadotrophin
Authors: Brand Egenius C. , Odink Jacobus
Published: December 2008

125I labelled desialylated hCG (asialo-hCG) was treated with galactose oxidase, in order to find out whether oxidation of the terminal galactosyl residues would diminish the hepatic uptake of asialo-hCG. Specific binding to the hepatic asialo-glycoprotein receptor was monitored in vitro by a rat liver radioligand receptor assay (RRA). Hormonal activities were compared by ovarian RRA and by in vitro bioassay. Uptake studies were done in superovulated immature rats. Galactose oxidase treatment had hardly any influence on the in vitro ovarian binding and biological activity of [125I]asialo-hCG. Binding in the liver RRA was virtually abolished. In vivo hepatic uptake, however, was considerably above the level of [125I]hCG, as was the uptake in the kidneys. The hepatic uptake was inhibited by the administration of a high dose of asialo-fetuin.

It is concluded that oxidation of the terminal galactosyl residues reduces the binding of asialo-hCG to the hepatic asialo-glycoprotein receptor, without affecting its hormonal properties. The ovarian uptake in vivo, however, is still limited by the high hepatic and renal clearance.
Hydroxylation of testosterone in the human testis Identification of 4-androstene,7α,17β-diol-3-one (7α-hydroxytestosterone) as a metabolite of testosterone
Authors: Sunde A. , Tveter K. , Eik-Nes K. B.
Published: December 2008

Homogenates of normal or cryptorchid, human testes were incubated with [3H]testosterone and a NADPH-generating system. [3H]4-andostene,7α,17β-diol-3-one (7α-OH-testosterone) was isolated and identified from such incubations. To our knowledge this is the first demonstration that 7α-OH-testosterone is a metabolite of testosterone in the human testis. 4-Andro-stene,6β,17β-diol-3-one (6β-OH-testosterone) and 4-androstene,16α,17β-diol-3-one (16α-OH-testosterone) were also identified as testosterone metabolites. The specific activity of both testosterone 6β- and 16α-hydroxylase was higher than that of 7α-hydroxylase. Pre-pubertal or cryptorchid human testis tissues seem in our study to have higher testosterone 6β- and 7α-hydroxylase activity than normal adult testis tissue.
A comparative study of the action of several lutropin derivatives on rat Leydig cells
Authors: de la Llosa-Hermier M. P. , Tertrin-Clary C. , Evrard-Herouard M. , Colleaux Y. , Hermier C. , de la Llosa P.
Published: December 2008

Rat intestinal cells prepared from testes were incubated in the presence of different lutropin derivatives obtained by chemical modification of the amino groups. The cAMP accumulation and the testosterone biosynthesis were determined in the cell homogenates. Binding determinations were carried out by a radioligand receptor assay using tritiated methylated lutropin. The binding activities — relative to native LH — of three different derivatives obtained by reductive alkylation (methylated, ethylated and isopropylated LH) were in good agreement with the relative potencies assessed by their capacity to stimulate cAMP and testosterone production. Guanidinated LH (11 — NH2 groups modified) exhibited a binding activity and a relative potency relatively high with regard to cAMP accumulation (as compared with that of native LH). Its steroidogenic potency, however, was very low. When Leydig cells were incubated in the presence of native and guanidinated LH, the testosterone production was similar to that induced by the derivative alone, indicating that the derivative exerted a competitive inhibitory action preventing the stimulation of steroidogenesis by native LH. These results suggest that a guanidinated derivative is able to bind to the LH receptor and the complex so formed is able to be coupled with an adenylate cyclase pool (or cAMP compartment) which is not connected with the steroidogenic pathway.
Pituitary response to LRH and TRH stimulation and peripheral steroid hormones in conscious and anaesthetized adult male rhesus monkeys (Macaca mulatta)
Authors: Wickings E. Jean , Nieschlag E.
Published: December 2008

Adult male rhesus monkeys are aggressive animals and very difficult to handle. Hence experimental manipulations necessarily involve the use of restraint procedures, either chemical or physical, which may influence endocrine functions. Therefore, the effects of ketamine anaesthesia on basal hormone levels and on the pituitary response to LRH and TRH were investigated in 4 adult male rhesus monkeys. Values were compared to those obtained from the same animals restrained in primate chairs for approximately 48 h, a procedure to which they had been accustomed to over the preceding 6 months.

Serum cortisol levels under anaesthesia were at all times lower than in conscious monkeys, but increased after 2 h to values twice as high as measured initially. Serum testosterone concentrations were not significantly different on the two occasions, but levels under anaesthesia were slightly higher initially than in the conscious monkeys, and decreased gradually over the 3 h test period. Initial prolactin levels were lower in the anaesthetized monkeys, and increased 2–3-fold after 90 min; values at 3 h were not significantly different from those in conscious monkeys. Intravenous TRH elicited a similar response in prolactin on both occasions, maximum values occurring after 15–30 min and returning to basal levels after 3 h. The maximum values attained and the area under the response curves were higher under anaesthesia. LRH stimulation resulted in a 15- and 30-fold increase in serum levels of biologically active LH, with and without anaesthesia, respectively. Basal levels were not significantly different on the two occasions. The area under the LH response curve was higher in 3 of the 4 monkeys without anaesthesia.

The extent to which results in conscious monkeys are affected by stress is difficult to assess. Since neither handling technique allows for the collection of 'true' basal data, it is paramount to standardize and define the conditions under which experiments, and even routine blood sampling, are performed in male rhesus monkeys.
Effects of propylthiouracil and relatively small doses of iodide on early phase treatment of hyperthyroidism
Authors: Kasai Kikuo , Suzuki Hitoshi , Shimoda Shin-Ichi
Published: December 2008

In order to compare the acute effects of three methods of treatment in hyperthyroid patients with diffuse goitre, values of thyroxine (T4), triiodothyronine (T3) in serum, T3-resin uptake (T3-U), free thyroxine index (FT4I) and free triiodothyronine index (FT3I) were employed as thyroid function parameters. In iodide (I−) group given iodine (3 or 6 mg/day) as iodinated lecithine once daily, the parameters were reduced acutely within one week after the start of treatment, reaching a plateau during the next week. In contrast to the changes in I− group, the thyroid function was decreased gradually and consistently for two weeks in the propylthiouracil (PTU 300 mg/day) group. In PTU + I− (300 mg/PTU plus 3 or 6 mg/iodide/day) group, the parameters were reduced acutely and progressively for two weeks. These results indicate that PTU +I− therapy is much more effective than PTU or I− alone in early phase treatment of hyperthyroidism. Another new finding was that the thyroid function increased again during the later addition of PTU (300 mg/day) in the patients treated with I− (3 or 6 mg/day) for one or two weeks. The well-known escape phenomenon from iodide inhibition took place counteracted the effect of PTU. Since blocking of thyroidal secretion by I− is only transient while synthesis of T3 and T4 continues, leading to greater amount of hormone stored in the gland, the treatment of hyperthyroidism with I− alone is a risky procedure.
Estimation of hormonal and non-hormonal iodine uptake from maternal milk in suckling rats
Authors: Vigouroux E. , Rostaqui N. , Fénerole J. M.
Published: December 2008

Maternal milk may carry hormonal iodine and thus contribute to a high thyroxine secretion level in suckling rats. In order to evaluate this possibility, milk iodo-compounds were estimated in rats equilibrated with 125I. On day-10 post partum, the milk contained 195±65 ng/ml iodine composed of 43 ng/ml iodide, 148 ng/ml non-hormonal organic iodine and only 3 ng/ml hormonal iodine. The stomachs of the sucklings contained 0.70 ± 0.05 and 1.2 ± 0.3 μg iodine/organ on days 10 and 20, respectively. The quantity of hormonal iodine was negligible compared with the amount of iodide and non-hormonal organic iodine. After enzymic proteolysis of the milk and stomach contents of the sucklings, 80–90 per cent of the non-hormonal organic iodine found was monoiodoryrosine (MIT), while the rest was diiodotyrosine (DIT).

Sixteen hours after injecting [131I]iodide and [125I]thyroxine into the mothers not equilibrated with 125I, on day-10 0.87 ± 0.10 per cent dose/ml of [125I]T4 was found in maternal plasma, 0.2–0.4 per cent dose/ml in milk, while only 0.05 ± 0.01 per cent dose/organ and 0.008 ± 0.002 per cent dose/ml was found in the stomachs of the sucklings and in plasma, respectively. By contrast, 131I rapidly disappeared from the maternal plasma and appeared in relatively high levels in the serum of the young. These results indicate that milk thyroxine is partially destroyed in the gut of the suckling. Maternal milk is a source of iodide and non-hormonal protein bound iodine in sucklings and does not contain any hormonal iodine.