bluuebunny/crossref_metadata_2025 huggingface dataset:
Diurnal rhythms of immunoreactive N-acetylserotonin and melatonin in the serum of male rats
Authors: Pang S. F. , Yip M. K. , Liu H. W. , Brown G. M. , Tsui H. W.
Published: December 2008

Immunoreactive N-acetylserotonin and melatonin in rat serum were extracted by ethyl acetate at ≤ pH 3 and chloroform at ≥ pH 10. respectively, following protein precipitation and were quantified by radioimmunoassays. There were diurnal rhythms of N-acetylserotonin and melatonin in the serum of rats (housed in 121/12d; lights on from 06.00–18.00 h for two weeks). Serum melatonin levels at 20.00–04.00 h are higher than those at 08.00–16.00 h. Serum N-acetylserotonin levels were, however, higher at 24.00–08.00 h and lower at 12.00–20.00 h. The concentration of N-acetylserotonin in individual samples ranged from a minimum of 0.45 ng/ml at 12.00 h to a maximum of 2.78 ng/ml at 08.00 h. The diurnal study on N-acetylserotonin levels in the rat serum was repeated and a similar result was obtained. The findings of the presence of N-acetylserotonin in the rat serum and a diurnal rhythm of serum N-acetylserotonin are in keeping with the notions that N-acetylserotonin may be secreted by the pineal gland and that N-acetylserotonin may be another indole with hormonal activities.
Distribution volume, metabolic clearance and plasma half disappearance time of exogenous luteinizing hormone releasing hormone in normal women and women with obesity and anorexia nervosa
Authors: Chikamori Kazumasa , Suehiro Fumie , Ogawa Toshiki , Sato Kei , Mori Hiroyoshi , Oshima Ichiyo , Saito Shiro
Published: December 2008

Synthetic LRH was infused into normal women and women with obesity and anorexia nervosa to determine the distribution volume (DV), metabolic clearance rate (MCR) and half disappearance time (t½) of plasma LRH.

In normal women, the DV of LRH was 12.1 ± 0.9 (mean ± se) l, the MCR was 1478.9 ± 39.8 ml/min (28.5 ± 1.2 ml/min/kg body weight) and the initial t½ was 5.6 ± 0.4 min.

In obese patients the DV (20.6 ± 1.5 l) was significantly higher than that in normal subjects (P < 0.005), but the MCR and t½ were not significantly different from those in normal subjects.

In patients with anorexia nervosa the DV and MCR were 6.5 ± 1.1 l and 621.8 ± 110.5 ml/min (17.9 ± 2.4 ml/ min/kg body weight), respectively, which were both significantly lower than those in normal subjects (P < 0.02), while the t½ (7.3 ± 0.1 min) was longer than in normal subjects (P < 0.02).

These data suggest that 1) the abnormal responses of some hormones to provocation tests observed in obese patients and patients with anorexia nervosa should be evaluated in consideration of changes in the DV and metabolic clearance of hormones in these conditions, and 2) in patients with anorexia nervosa changes in MCR and t½ may reflect low metabolism of LRH.
New aspects of the physiological significance of LRH receptors of pituitary plasma membranes
Authors: Kuhl Herbert , Baumann Rudolf
Published: December 2008

It has been found that l-cystine-bis-(4-nitroanilide), a synthetic peptidase substrate, competes with [125I]LRH for specific high affinity LRH receptors on isolated rat pituitary plasma membranes as effectively as a highly active LRH analogue. The pattern of [125I]LRH degradation by isolated pituitary plasma membranes was similar to that effected by pituitary and hypothalamic enzyme extracts. The enzyme activity seemed to accumulate in the supernatant of the membrane suspension after being released from the membrane structure.

Plasma membrane supernatant and pituitary and hypothalamic enzyme extracts were chromatographed together with labelled LRH on Sephadex G 200. This resulted in protein binding patterns with one peak at the fractions representing a molecular weight of 600 000 to 650 000 and another one of approximately 80 000, the first probably being an aggregate of the latter. After solubilization of the plasma membranes by Triton X-100, there was no evidence for another LRH receptor. There were also two peaks of [125I]LRH degrading activity (with identical metabolic pattern) and two peaks of arylamidase activity, which were, however, not identical with the binding peaks.

Both the arylamidase and the LRH binding-pattern had been demonstrated to be temperature- and hormonedependent, and seemed to be functionally related. The results indicate that there is a functional relationship between LRH binding-sites on plasma membranes and LRH degrading enzymes. This implies that the search for the 'true' LRH receptor has to be directed towards intracellular compartments of the pituitary gonadotrophs.
Quantitative studies of vasoactive intestinal peptide (VIP) binding sites and VIP-induced adenosine 3′:5′-monophosphate production in epithelial cells from duodenum, jejunum, ileum, coecum, colon and rectum in the rat
Authors: Prieto Juan C. , Laburthe Marc , Hoa Danièle Hui Bon , Rosselin Gabriel
Published: December 2008

The binding of vasoactive intestinal peptide (VIP) and its effect on adenosine 3′:5′-monophosphate (cyclic AMP) production were measured in isolated rat intestinal epithelial cells from duodenum, jejunum, ileum, coecum, colon and rectum. In every segment tested, VIP binding and VIP-induced cyclic AMP production exhibited a similar pattern with two populations of VIP binding sites and similar magnitude of cyclic AMP production. Continuous displacement of the binding of 125I-labelled VIP and stimulation of cyclic AMP production were observed in the range of 10−10–10−7 m VIP concentrations. Fifty per cent inhibition of the initial binding of tracer was obtained with 2.2 to 3.2 nm VIP. The Km of stimulation of cyclic AMP production was 1.2 to 2.6 nm VIP.

Chicken VIP and porcine secretin showed a 4-fold higher and a 100-fold lower affinity than porcine VIP for binding sites, respectively. The same was true for the stimulation of cyclic AMP production.

The existence of receptors highly sensitive to VIP in the separate segments of the bowel corresponds to the presence of high concentration of VIP at the vicinity of epithelial cells and strongly suggests that VIP is active in regulating different intestinal functions.
Congenital adrenal hyperplasia due to partial 21-hydroxylase deficiency. A study of five cases
Authors: Bouchard Philippe , Kuttenn Frederique , Mowszowicz Irene , Schaison Gilbert , Raux-Eurin Marie-Charles , Mauvais-Jarvis Pierre
Published: December 2008

Five women with post pubertal hirsutism due to a partial 21-hydroxylase deficiency were studied. These patients had no abnormalities of the external genitalia. They were compared to 3 adult women with a complete defect in 21-hydroxylase. The diagnosis of 21-hydroxylase deficiency was substantiated by the dramatic increase in 17-hydroxyprogesterone (17-OHP) after im injection of 250 μg synthetic ACTH (22 ± 12 nmol/l to 349 ± 153 nmol/l). However, in adult women with 21-hydroxylase deficiency recognized at birth and presenting abnormalities of the external genitalia, plasma 17-OHP was elevated in basal conditions (512 ± 106 nmol/l) and only slightly increased after ACTH administration (657 ± 133 nmol/l). Plasma cortisol levels determinated at 08.00 h were lower than normal in both groups but only slightly in groups with partial 21-hydroxylase deficiency. After ACTH stimulation, plasma cortisol levels remained lower than normal in all patients but with a noticeable increase in patients with partial defect. The differences noted between precocious and delayed onset virilization gave an indication of the importance of the enzyme defect. Plasma testosterone (T) and androstenedione (Δ4) levels were elevated both in basal conditions and after ACTH administration. However, in patients with delayed onset of hirsutism most circulating T seems to originate from peripheral conversion of Δ4 to T. Plasma ACTH values were strongly elevated in patients with a complete defect in 21-hydroxylase (260 ± 50 pg/ml) but normal in patients with partial deficiency (< 40 pg/ml).

In vitro testosterone 5α-reductase activity was determined in pubic skin homogenates from 4 patients with partial 21-hydroxylase deficiency. The amount of dihydrotestosterone + androstanediols formed from incubated [3H]testosterone was in the normal range for women. Virilization of patients with partial 21-hydroxylase deficiency therefore seems to be essentially due to an increase in active androgen production and not to exaggerated skin 'utilization' of pre-androgens as observed in idiopathic hirsutism.
Testosterone, dihydrotestosterone and androstanediols in plasma, testes and prostates of rats during development
Authors: Corpéchot Colette , Baulieu Etienne-Emile , Robel Paul
Published: December 2008

Testosterone (T). 5α-dihydrotestosterone (DHT), 5α-androstane-3α, 17β-diol (3α-diol), and 5α-androstane-3β,17β-diol (3β-diol) have been measured in the plasma, ventral prostate, and testes of Sprague-Dawley rats with a specific radio-immunoassay, at birth, and then weekly until the 12th week.

In plasma, the T concentration is ∼ 0.3 ng/ml at birth and up to the 4th week; thereafter it increases steadily and reaches the adult level of ∼ 3 ng/ml by the 8th week. In male foetuses of 18 days gestation, the plasma concentration is 0.6 ng/ml. The 5α-metabolites taken together are at a higher concentration than that of T until the 7th week, and each one, after a broad maximum between 5–9 weeks, decreases promptly by the 10th week. The larger formation of 5α-metabolites from T in young rats has been confirmed by injection of the hormone to castrated males, which showed relatively more conversion at 5 than at 10 weeks.

In the ventral prostate, DHT is already high at 4 weeks (11 ng/g), and remain between 7 and 15 ng/g until the 12th week. T concentration is also larger than in plasma at 4th week (2 ng/g) and becomes approximately equal to the plasma value at puberty. A sharp peak of 3α-diol and 3β-diol is observed at the 8th week.

In the testes, T concentration is high at birth (183 ng/g), then declines rapidly, and increases again from the 5th week onward in parallel with plasma concentration. The concentrations of 5α-metabolites per testis vary in parallel to those in plasma, with the exception of sustained elevation of 3β-diol.
Age-related changes in the feedback regulation of gonadotrophin secretion by sex steroids in men
Authors: Muta Kazuo , Kato Ken-ichi , Akamine Yasuo , Ibayashi Hiroshi
Published: December 2008

In order to clarify the age-related functional changes of the hypothalamic-pituitary-gonadal axis in men, the negative feedback control of serum gonadotrophin by sex steroids was studied in 39 young (18–34 years) and 49 elderly (62–95 years) men. Mean basal LH and FSH levels and the responsiveness to synthetic LRH were determined before and after daily im injection of testosterone propionate (TP; 5, 10 or 50 mg/day) or oestradiol benzoate (OeB; 50, 100 or 500 μg/day) for 3 days.

After the administration of TP or OeB, serum levels of testosterone or oestradiol were more elevated in the elderly than in the younger group. In the latter, basal LH level decreased significantly at 10 mg/day of TP and so did basal levels of both LH and FSH at 50 and 100 μg/day of OeB. Responses of serum LH and FSH to LRH were inhibited significantly by TP at a dose of 50 mg/day and by OeB at doses of 100 and 500 μg/day. Whereas in the elderly group, basal LH levels and responses of both LH and FSH were not suppressed significantly by TP regardless of the dose. At a dose of 500 μg OeB, serum LH response was decreased remarkably. Per cent suppression of serum LH response at 50 mg TP, as well as those of serum LH and FSH responses at 500 μg OeB in the elderly group, was significantly less than in the younger group. These data indicate that in the elderly men the regulatory system of gonadotrophin secretion appears to manifest a more marked resistance to inhibitory effects of sex steroids, and also suggest that the set-point to sex steroids in the hypothalamic-pituitary axis is reset at a higher level in male senescence.
Congenital familial thyroid aplasia
Authors: Stäger J. , Froesch E. R.
Published: December 2008

A family with 4 siblings, 3 of which have hypothyroidism due to thyroid aplasia is described. A review of the literature revealed 10 families with familial occurrence of this disorder without other malformations. Therefore, thyroid aplasia or dysplasia should no longer be called 'sporadic cretinism' since autosomal recessive inheritance of this disorder appears to occur rather frequently.
A radioimmunoassay for human parathyroid hormone utilizing a goat anti-bovine PTH serum
Authors: Mallette L. E.
Published: December 2008

An antiserum (NG-1) against bovine PTH (bPTH) generated in the domestic goat was characterized for use in the radioimmunoassay of PTH in human serum. When a carboxyterminal fragment of bPTH is used as radioligand, this antiserum detects only an antigenic site in the central region of the hPTH molecule. The synthetic hormone fragment, hPTH-(44-68), will displace 93% of the tracer, after which the addition of intact hPTH causes no further displacement. The assay does not detect the synthetic aminoterminal 1-34 fragment of the bovine or human hormones, nor the carboxyterminal fragment of the human hormone, hPTh-(53-84). Standard curves with bPTH-(1-84) and partially purified hPTH are not parallel, so that hPTH is used as standard. Serum from subjects with uraemia or primary hyperparathyroidism gives dilution curves parallel to that with the hPTH standard. The assay with NG-1 has been applied to the diagnosis of primary and secondary hyperparathyroidism, used to monitor the disappearance of PTH after parathyroidectomy, and for measurement of PTH in selective venous samples.
A change in the adrenocortical response in perinatal rat offspring given betamethasone 17,21-dipropionate
Authors: Hasegawa Y. , Yoshida T. , Fukiishi Y. , Mizushima Y.
Published: December 2008

The potent synthetic glucocorticoid betamethasone 17,21-dipropionate (BMDP) produces adrenal hypertrophy in the rat foetus at late pregnancy by mediation of the hypothalamo-pituitary system, but causes adrenal atrophy, and acts as a normal glucocorticoid, in the adult rat. The change of the adrenal cortical response to the BMDP treatment was investigated in perinatal rat offspring. The pituitary ACTH potency was also determined in rat foetus treated with BMDP.

The time course of the adrenal corticosterone level after the BMDP treatment was similar to that of the plasma level on day 19 to 21 in the rat foetus from the adrenalectomized mother, both decreased at 2 h, but rose gradually at 4 h to 6 h, exceeding the control level at 24 h and 48 h after the BMDP treatment. The pituitary ACTH potency in the foetus decreased at 24 h and 48 h after the BMDP treatment, suggesting that ACTH released from the foetal pituitary stimulated adrenal corticoidogenesis. Maternal adrenalectomy did not essentially alter this stimulating activity of BMDP, which appeared in the perinatal rat offspring, only when BMDP was administered during the foetal period. These findings suggest that the hypothalamo-pituitary adrenocortical response to the treatment with BMDP drastically changes at the early neonatal age.
Recovery of the pituitary gland from LRH-induced refractoriness to LRH in the ovariectomized rat
Authors: Koiter T. R. , Pols-Valkhof N. , Schuiling G. A.
Published: December 2008

Recovery of the pituitary gland from LRH-induced refractoriness to LRH was studied in 5-weeks ovariectomized rats. Rats first received over a period of 48 h an infusion of LRH at a rate of 416 ng/h. After discontinuation of this infusion pituitary LH content had decreased to about 50% of its original value and the rate of LH secretion decreased markedly. Over a period of 72 h after discontinuation of the infusion plasma LH values rose to pre-infusion values but pituitary LH content showed such a recovery only partly.

In another series of experiments a second infusion of LRH was given during 24 h and again at a rate of 416 ng/h, starting 3, 12, 24 or 72 h after discontinuation of the first infusion. It induced rises of LH secretion which were smaller than those following the first infusion, indicating refractoriness of the pituitary gland to LRH. However, the LH responses became progressively larger with increasing time intervals after the end of the first infusion. This stimulation of LH release was accompanied by a further decrease of pituitary LH content which was still depressed after the first infusion.

Comparison of plasma LH levels and pituitary LH content indicated that pituitary responsiveness to LRH can recover independently from pituitary LH content. It can also be concluded that the absolute value of the blood LRH concentration can not be the sole determining factor of LH secretion.
Regarding the validity of the endpoint response of the mouse (McKenzie) bioassay for thyrotrophin (TSH)
Authors: Ching Melvin
Published: December 2008

The release of radiolabelled thyroid hormone into the circulation in low iodine fed mice has been used extensively as a bioassay for thyroid stimulating hormone (TSH). However, the specificity of several bioassays of pituitary hormones have been subject to question. Consequently, the validity of the assay endpoint for TSH in the mouse was re-evaluated with respect to the effect of luteinizing hormone (LH) whose chemical composition closely resembles that of TSH. Mice, prepared for bioassay of TSH received injections of purified LH or α or β subunits of LH. Identical doses of LH and LH subunits were quantified by LH and TSH radioimmunoassays and the results compared with those obtained by the bioassay. Microgram quantities of LH and subunits of LH elicited appreciable responses in the TSH bioassay but produced only negligible effects in the TSH radioimmunoassay. The response of the TSH bioassay of LH and α or β subunits of LH was 40–56% that obtained with LH radioimmunoassay. However, the pituitary concentrations obtained by TSH bioassay when compared with those obtained by radioimmunoassays for TSH, LH, or growth hormone (GH) paralleled closely the TSH radioimmunoassay data, although in terms of quantitative estimates, there was a 15-fold discrepancy between the TSH assays. Estimations of pituitary concentrations of LH lead to the conclusion that, at the doses normally employed, most crude rat pituitary extracts do not contain sufficient quantities of LH to alter significantly bioassayable (McKenzie) estimates of TSH.
Characterisation of breast skin temperature rhythms of women in relation to menstrual status
Authors: Phillips M. J. , Wilson D. W. , Simpson H. W. , Fahmy D. R. , Groom G. V. , Phillips M. E. A. , Pierrepoint C. G. , Blamey R. W. , Halberg F. , Griffiths K.
Published: December 2008

Circadian breast skin temperature rhythms were characterised throughout the menstrual cycle, for various locations on the left breast of ambulatory women. All subjects exhibited highly significant circadian rhythms (P < 0.001). Changes in rhythm parameters, such as the mesor, amplitude and acrophase, were observed during the menstrual cycle. No consistent trend in these rhythm parameters was observed between subjects in relation to menstrual cycle stage. Experimental and statistical techniques used to characterise circadian rhythms in pre-menopausal women were applied to a post-menopausal woman with primary breast cancer. Comparison of rhythm parameters associated with the tumour area and corresponding site on the contralateral breast showed abnormal thermal characteristics such as elevated mesor values, decreased amplitude as well as changes in the timing of the acrophase. These properties may be exploited for the early detection of breast cancer. The project also involved the design and testing of an ambulatory device, known as the 'chronobra', for the measurement of breast skin temperature. The performance of the chronobra was in close agreement with reliable, conventional equipment. The chronobra now allows studies of breast skin temperature rhythms associated with breast disease to be extended.
Degradation of human chorionic gonadotrophin by human and rat tissues in vitro
Authors: Markkanen S. O. , Rajaniemi H. J.
Published: December 2008

To determine what tissues are capable of degrading human chorionic gonadotrophin (hCG) in vitro, 125I-labelled hCG was incubated in various rat and human tissue homogenates. Some of the properties of the enzymes involved in the degradation processes were elucidated using enzyme modifiers. Degradation products of the hormone were analysed by gel filtration. In the liver and kidney homogenates the hormone was degraded into peptide fragments similar to the hormone subunits and further to smaller peptides and amino acids. Also blood cells, ovaries and human placenta were capable of cleaving the hormone into the subunits. The pH-optimum of the degradation reactions was 6.5. EDTA, DTT and 0.05% Triton X-100 slightly activated the reactions. Alkylating agents, such as N-ethylmaleimide and iodoacetamide inhibited both the subunit cleavage and the peptidolysis. Instead heavy metals, Hg2+, Cu2+ and Zn2+ inhibited mainly the peptidolysis. Phenylmethyl sulphonyl fluoride and ovomucoid trypsin inhibitor had no or a slight inhibition. An excess of unlabelled hCG or insulin inhibited the degradation reactions. The present results indicate that [125I]hCG is inactivated by the cleavage of the peptide fragments similar to the hormone subunits and peptidolysis and that different enzymes requiring free thiol-group(s) are involved in these processes. The observation of the degradation of [125I]hCG in placental tissue may have clinical significance in complicated pregnancies.
Stroma of human benign prostatic hyperplasia: preferential tissue for androgen metabolism and oestrogen binding
Authors: Krieg M. , Klötzl G. , Kaufmann J. , Voigt K. D.
Published: December 2008

Because of the well known stromal-epithelial interaction of various urogenital organs, it was of interest to compare quantitatively steroid metabolism and binding in epithelium (E) and stroma (S) of the human benign prostatic hyperplasia (BPH).

Testosterone 5α-reductase activity was determined by thin-layer chromatography and androgen as well as oestrogen binding sites by a charcoal adsorption technique after a steroid incubation period of 18 h at 0°C, using methyltrienolone (R1881) and oestradiol-17β as tritiated ligands and unlabelled R1881 and diethylstilboestrol as the respective competitors.

The main results were as follows: (1) using biochemical markers (acid phosphatase, hydroxyproline), an on average 17% contamination of E by S and 6% of S by E was found, (2) the molar optimum of NADPH for the enzyme reaction was nearly identical in E and S, ranging between 1 and 0.1 mm, (3) the apparent Michaelis constant (Km) of 5α-reductase was in both fractions identical, the mean being 0.15 (μm, (4) the maximal rate of 5α-reductase activity (pmol 5α-reduced metabolites · mg protein−1 · 1 h−1) was 161 ± 28 (sem; n = 20), 66 ± 4.6 and 148 ± 6.6 in S, E and whole tissue fraction of BPH, respectively. In two normal prostates the means were: 88, 53 and 73, respectively, (5) the androgen binding sites were evenly distributed between the cytosol of E and S, while measurable oestrogen binding sites were found in 42% of the analyzed S but only in 5% of analyzed E.

In conclusion: the 2.4 times higher 5·-reductase activity in S compared to E of the BPH is responsible for the about 2 to 2.5 times higher activity in the whole tissue fraction of BPH if compared with the normal prostate. Furthermore, due to our preliminary binding studies, oestrogens might play an important role in the S fraction of BPH.
Dose related effects of betamethasone on iodothyronines and thyroid hormone-binding proteins in serum
Authors: Gamstedt Anders , Järnerot Gunnar , Kågedal Bertil
Published: December 2008

Earlier studies of the effect of glucocorticoids on thyroid function tests have given different results. This may be due to the fact that varying corticosteroid doses have been used. The present study examines four groups of healthy volunteers, who were given betamethasone in increasing doses (1.5, 3.0, 4.5 and 6.0 mg daily) for 5 days. Definite dose-response relations were found for serum T4 and T3 while no clear-cut dose-response pattern was found for rT3. The results obtained explain previous variable results. Oral corticosteroids also affected the concentrations of the thyroid hormone-binding proteins but no clear-cut dose-response relation were observed.
Effects of octanoate and ketone bodies on the structure and function of isolated pancreatic islets in tissue culture
Authors: Borg L. A. H.
Published: December 2008

To study the effects of fatty acids and ketone bodies on both insulin release and lasting changes in ultrastructure and function of the pancreatic B-cell, isolated mouse islets were cultured for one week in the presence of either octanoate, acetoacetate or 3-hydroxybutyrate. The glucose concentration of the unsupplemented culture medium was 3.3 mmol/l and islets cultured in this medium were used as controls. It was found that octanoate stimulated insulin accumulation in the culture medium, decreased the islet insulin content and also effected a degranulation of the islet B-cells. Although there was no significant change in the total mitochondrial volume of the octanoate cultured islets, the activity of the mitochondrial marker enzyme L-3-hydroxyacyl-CoA-dehydrogenase was decreased. In short-term incubations performed after culture with octanoate, there was an increased rate of islet protein biosynthesis, which seemed to be independent of a glucose challenge. After culture of islets with acetoacetate, morphometrical measurements indicated an increased islet cell size, but there appeared to be no further effects of this ketone body on the islet ultrastructure or function. 3-Hydroxybutyrate, however, increased both the insulin accumulation in the culture medium and the insulin content of the cultured islets. Apparently, the β-granule content of the islets exposed to 3-hydroxybutyrate also increased. Furthermore, there was a reduction in the total mitochondrial volume of the 3-hydroxybutyrate cultured islets. In addition, the activity of L-3-hydroxyacyl-CoA-dehydrogenase was reduced, whereas islet glucose oxidation was markedly increased. In conclusion, therefore 3-hydroxybutyrate greatly resembled glucose in its effects on the islet B-cells.
Increased thyrotrophin and prolactin secretion induced by domperidone in hypothyroid subjects
Authors: Massara F. , Camanni F. , Amoroso A. , Molinatti G. M. , Müller E. E.
Published: December 2008

The thyrotrophin (TSH) and prolactin (Prl) releasing effects of domperidone, a recently developed antidopaminergic drug which does not cross the blood-brain barrier, were investigated in 8 women affected by primary hypothyroidism, and were compared to those elicited by another antidopaminergic drug, sulpiride. Domperidone (4 mg iv) induced a clear-cut and sustained rise in both plasma TSH and Prl, with peak levels occurring 15 and 30 min post-injection, respectively. The increments in plasma Prl after domperidone were significantly higher than those in plasma TSH. The TSH and Prl responses induced by domperidone were almost superimposable to those provoked in the same subjects by sulpiride (100 mg im). In view of the inability of domperidone to penetrate into the central nervous system (CNS), these findings imply a 'peripheral' site(s) of action (i.e., anterior pituitary and/or median eminence) for the effect of antidopaminergic drugs on TSH secretion, and, re-iterate the notion that the same 'peripheral' sites are involved in the Prl-releasing effect of these compounds.
Increase in thyroxine-binding globulin (TBG) in lysinuric protein intolerance
Authors: Lamberg B.-A. , Perheentupa J. , Rajantie J. , Simell O. , Saarinen P. , Ebeling P. , Welin M.-G.
Published: December 2008

The common occurrence of increased serum PBI concentration in patients with lysinuric protein intolerance (LPI) was elucidated by further studies. The reason was found to be an increase in the concentration of thyroid binding globulin (TBG), concomitantly with an increase in the binding capacity of TBG. The concentrations of serum thyroxine and triiodothyronine were elevated, whereas the free thyroxine index remained normal. The free triiodothyronine index was slightly increased. The binding capacity of thyroid hormone binding pre-albumin (TBPA) was significantly decreased. The concentrations of reverse triiodothyronine (3,3',5'-T3) and of 3,3'-diiodothyronine were normal. In all patients serum lactic acid dehydrogenase activities and ferritin concentrations were elevated.

The reason for the almost constant increase in TBG remains obscure. It may be related to the primary disorder of LPI, a defect in diaminoacid transport.
Effect of meclastine, an H1-antihistamine, on plasma ACTH in adrenal insufficiency
Authors: Allolio B. , Winkelmann W. , Hipp F. X.
Published: December 2008

In order to evaluate the possible role of endogenous histamine in ACTH secretion we investigated the effect of the H1 antagonist meclastine on plasma ACTH in patients with ACTH hypersecretion. Seven patients with primary adrenal insufficiency (group 1) and 5 patients with ACTH dependent Cushing's syndrome (group 2) were given an iv infusion of meclastine (4.8 mg/90 min). In patients of group 2 plasma ACTH was unaffected by meclastine infusion. However, in patients of group 1 with intact steroid feedback meclastine was followed by a significant drop in plasma ACTH as compared with ACTH levels after saline infusion (46.0 ± 4.6% vs 85.0 ± 7.0%, P < 0.01). These results suggest that histamine is involved in the control of ACTH secretion, possibly by stimulation of CRF release.
Studies on the biological and immunological properties of human follitropin: profiles of two international reference preparations and of an aqueous extract of pituitary glands after electrofocusing
Authors: Zaidi A. A. , Robertson D. M. , Diczfalusy E.
Published: December 2008

Two international reference preparations, the First International Reference Preparation of Human Pituitary Gonadotrophins (FSH and LH/ICSH) for Bioassay (identified hereafter by its code no.: 69/104) and the First International Standard of Urinary FSH and LH (ICSH) for Bioassay (hereafter: hMG 1st IS) and an aqueous extract of human pituitary glands (hPE) were fractionated in triplicate by isoelectric focusing on sucrose density gradient (Ampholine, pH range 2.5–10.0). The FSH activity was monitored in each fraction by an in vitro bioassay, a radioimmunoassay and a receptor binding assay. Unfractionated 69/104 was used as standard in each assay system.

Compared with the hPE, the activity profiles of the 69/104 and hMG reference preparations were spread over a significantly wider pH range; the biological activity eluted in the pH range of 3.5–5.0 was of the order of 90% for hPE, 72% for 69/104 and less than 60% for hMG.

Major variations in biological to immunological (B/I) and biological to receptor binding (B/R) activity ratios were observed in the individual electrofocusing fractions. The B/I ratios ranged from 0.8 to 2.2 (69/104), 1.0–5.7 (hMG) and 1.3–6.0 (hPE), respectively. The variation in the corresponding B/R ratios was: 0.5–1.7 (69/104), 0.58–4.0 (hMG) and 0.55–1.5 (hPE). When equal aliquots from each of the electrofocusing fractions were combined and this 're-constituted' pool was compared with the starting material, significant differences were observed in the B/I ratios: 1.63 instead of 1.0 (69/104), 2.58 vs 2.34 (hMG) and 2.72 vs 1.32 (hPE). There was no significant change in the mean B/R ratios before and after electrofocusing: 1.0 vs 1.02 (69/104), 1.09 vs 1.02 (hMG) and 1.05 vs 1.04 (hPE).

The mean recovery of biological activity in each of the three reconstituted pools of the three preparations was 97% for 69/104, 88% for hMG and 98% for hPE, and the corresponding recoveries of receptor binding activities were 95%, 94% and 98%, respectively. In contrast, the mean recovery of immunological reactivity was only 55% (69/104), 80% (hMG) and 47% (hPE), respectively.

The reduction in the immunological reactivity of the 69/104 preparation without any apparent loss of biological or receptor binding activities following electrofocusing indicates that its immunoreactivity is unstable under mild experimental conditions, which do not influence its biological and receptor binding activities. Hence, whereas this preparation might possibly be suitable as a standard for in vitro bioassays and receptor binding assays, it is unsuitable as a standard for the radioimmunoassay of hFSH.
Force development and metabolism in skeletal muscle of euthyroid and hypothyroid rats
Authors: Everts M. E. , van Hardeveld C. , Keurs H. E. D. J. Ter , Kassenaar A. A. H.
Published: December 2008

The effects of thyroid hormone depletion on skeletal muscle metabolism in relation to force development were studied. For this purpose, the triceps surae muscles were perfused and stimulated at 5 Hz. The basal oxygen consumption of the skeletal muscle preparation was 50% lower in hypothyroid rats as compared with euthyroid rats.

The results show that:

1. Active force development was the same in euthyroid and hypothyroid rats during 30 min of stimulation.

2. The increase in oxygen consumption during contraction was twice as high in the euthyroid group compared with the hypothyroid group.

3. Lactate release and glucose consumption were considerably higher in the euthyroid group than in the hypothyroid group during the last 15 min of stimulation. The data show that force development is not impaired in hypothyroid rats but, on the contrary, indicate that the contraction process proceeds more economically in hypothyroid rats than in euthyroid rats.
Potentiation of prostaglandin E2-induced release of LH by the prostaglandin analogue, 7-oxa-13-prostynoic acid
Authors: Warberg Jørgen
Published: December 2008

The prostaglandin (PG) analogue 7-oxa-13-prostynoic acid (7-OPA) was infused into a lateral ventricle of the brain of adult male rats and the effect of the analogue on a subsequent stimulation of LH release by intraventricular infusion of PG's was determined. Pre-treatment of the animals with 44–132 μg of 7-OPA potentiated the stimulatory effect of 2 μg PGE2 on the release of LH but the analogue alone had no effect on the hormone secretion. The minimal effective dose of PGE2 was determined to be within the range 0.01–0.05 μg and it was found that priming with 132 μg of 7-OPA caused a formerly sub-threshold dose (0.01 μg) of PGE2 to become an effective stimulus for the release of LH. In contrast to its potentiating effect on PGE2-induced LH release 7-OPA did not alter the stimulatory action of PGF2α (2 μg) on the secretion of LH. 7-OPA had no effect on LRH-induced release of LH indicating that the PG analogue acts at a suprapituitary site to enhance PGE2-induced LH release. The potentiating effect of 7-OPA may be exerted at a binding site for PGE2 in the brain and the results suggest the existence of a different binding site for PGF2α. The possibility also exists that 7-OPA inhibit metabolic inactivation of PGE2.
Patterns of spontaneous LH release in normo- and hyperprolactinaemic women
Authors: Buckman Maire T. , Peake Glenn T. , Srivastava Laxima , Morris Josephine , David Barry , Shah Bharat
Published: December 2008

Hyperprolactinaemia may be associated with functional amenorrhoea. In order to evaluate the possible role of abnormal spontaneous LH secretion in hyperprolactinaemic amenorrhoeic women, plasma LH was measured at 15 min intervals for 300 min in 12 normal women during the early follicular phase of the menstrual cycle and compared to that observed in 11 hyperprolactinaemic amenorrhoeic subjects. Mean plasma prolactin was 9.1 ± 3.6 ng/ml (x̄ ± sem) in the euprolactinaemic and 168 ± 32 ng/ml in the hyperprolactinaemic group. Sex steroids including oestrone, oestradiol, progesterone and 17-hydroxyprogesterone were similar in the 2 groups. Mean plasma LH levels over the 300 min sampling period were 9.4 ± 1.6 mIU/ml in the normal subjects and 7.5 ± 1.0 mIU/ml in the hyperprolactinaemic patients (P>0.10). Every normal woman exhibited at least one LH spike in excess of 10 mIU/ml. Five hyperprolactinaemic patients failed to exhibit any LH spikes above 10 mIU/ml (P < 0.02 compared to controls). Thus, hyperprolactinaemia was associated with an absence of LH spike activity in 45% of patients studied and this abnormality may play an aetiologic role in the hypogonadism observed in these subjects; in those hyperprolactinaemic subjects with pulsatile LH secretion, however, other explanations for their amenorrhoea should be considered.
Dynamic evaluation of prolactin secretion with sulpiride and thyrotrophin releasing hormone in amenorrhoeic and normally menstruating women
Authors: D'Agata R. , Aliffi A. , Gulizia S. , Vicari E.
Published: December 2008

Sulpiride and TRH were used to evaluate the dynamics of prolactin (Prl) release in normoprolactinaemic, amenorrhoeic and normally menstruating women. The two tests were performed in a randomized order with an interval of 2—3 days. In the normal women the first test was carried out between days 2 and 4 of their cycle. Basal values during the two tests were not statistically different (9.6 ± 1.2 se vs. 10.7 ± 1.4 ng/ml in amenorrhoeic women with sulpiride and 11.3 ± 1.4 vs. 12.4 ± 1.7 in amenorrhoeic women during the TRH test). The two tests were performed while the subjects of the two groups had identical serum oestrogen concentrations. The Prl response following TRH administration was similar in both groups (Δmax [unk]49.5 ± 12.5 se and 49.4 ± 8.5 se in normal and amenorrhoeic women, respectively). In contrast, when release by sulpiride administration was studied the normal women had greater Prl release (Δmax [unk] 169.9 ± 18.2 se) than amenorrhoeic women (Δmax [unk] 99.8 ± 9.4). Either the different oestrogen status (lower in amenorrhoeic women than in menstruating women) or the hypothalamic pituitary dysfunction likely to be responsible for the amenorrhoea in our patients, may explain the lower Prl release observed after sulpiride in subjects with amenorrhoea.
The effects of water deprivation and water loading during treatment with 1-deamino-8-D-arginine vasopressin in central diabetes insipidus in childhood
Authors: Becker Dorothy J. , Foley Thomas P.
Published: December 2008

Nine children aged 72/12 to 179/12 years with central diabetes insipidus were subjected to water deprivation and water loading during treatment with 1-deamino-8-D-arginine vasopressin (DDVAP). Urine output remained unchanged despite the large differences in water intake. Serum osmolarity was not significantly affected by water deprivation. However, there was a marked decrease in serum osmolarity during water loading. This was not accompanied by any symptoms of haemodilution. Thus patients apparently tolerate large variations in fluid intake during therapy with DDVAP.
Syndrome of'inappropriate secretion of thyroid-stimulating hormone' by partial target organ resistance to thyroid hormones
Authors: De Diego J. Salmerón , Rodriguez C. Alonso , Orlando A. Salazar , Cervigon P. Sanchez Garcia , Mutazzi E. Caviola , Mateos J. M. Palacios
Published: December 2008

A 74 year old woman was found to have elevated serum thyroid-stimulating hormone (TSH) levels and elevated serum thyroid hormone levels, with clinical euthyroidism. There was no evidence of a pituitary tumour. TSH levels increased substantially during methimazole therapy. Administration of dexamethasone was followed by a prompt fall in serum TSH levels. Triiodothyronine (T3) was administered over a period of 20 days in doses from 25 μg to as much as 100 μg daily causing a rise in serum T3 above 700 ng/100 ml, a decline of T4 and a blunting of the response to thyrotrophinreleasing hormone (TRH), with normal metabolic responses (pulse rate, photomotogram, cholesterol).

These results suggest that the patient's disorder is due to partial target organ resistance to thyroid hormones.
Disappearance of insulin in man: variation with the plasma insulin level
Authors: Tranberg Karl-Göran , Hagander Per , Thorell Jan
Published: December 2008

Clearance rates of unlabelled insulin were studied in 45 unanaesthetized non-diabetic humans. The clearance rate, as well as the pancreatic secretion rate, of endogenous insulin was estimated from steady-state concentrations in portal and arterial blood. The clearance rate of exogenous insulin was determined after brief intraportal infusion.

In the basal fasting state, the endogenous plasma insulin level varied as closely with the clearance of endogenous insulin as with the rate of pancreatic secretion. During elevation of insulin by glucose infusion, it varied predominantly with the rate of insulin secretion. Clearance of exogenous insulin did not vary with the pre-test endogenous insulin level. The clearance of endogenous insulin increased from 11 ml · min−1 · kg−1 in the basal fasting state to 17 ml · min−1 · kg−1 during glucose infusion. Clearance of exogenous insulin fell progressively with increasing dose, from 35 (8 mU/kg) to 14 (43 mU/kg) ml · min−1 · kg−1 at normoglycaemia and from 23 (8 mU/kg) to 17 (34 mU/kg) ml · min−1 · kg−1 at hyperglycaemia. The clearance of endogenous insulin was lower than that of exogenous insulin at normoglycaemia, but of similar size during glucose infusion.

It is concluded that variation in clearance rate is partly responsible for variation in plasma insulin concentration, particularly in the basal fasting state, and that the clearance rate is lower in the basal state than otherwise. To some extent, the low clearance values for endogenous insulin in the basal state may reflect poor specificity of the insulin radioimmunoassay.
Plasma cyclic nucleotides and plasma catecholamines before and after prolonged treatment with clonidine in hypertensive patients
Authors: Manhem Per , Heding Lise , Malmquist Jörgen , Hökfelt Bernt
Published: December 2008

The effect of standing and physical exercise on catecholamines and cyclic nucleotides in plasma was measured in 8 patients with essential hypertension under standardized conditions before and after prolonged treatment with clonidine.

Before clonidine medication noradrenaline, adrenaline and cyclic AMP (cAMP) increased in response to standing and bicycling for 20 min. No significant correlation was found between their absolute levels nor was the increase in cAMP following exercise correlated to the increase in noradrenaline. Standing and physical exercise were without effect on cyclic GMP (cGMP).

Clonidine reduced the plasma noradrenaline concentration in supine position and the noradrenaline and the adrenaline response to standing and exercise. Plasma cAMP was uneffected by clonidine under basal conditions but the response to exercise was slightly reduced initially. During clonidine there was a positive correlation between the plasma levels of cAMP and noradrenaline following work. Clonidine produced an increase in plasma cGMP in supine position, immediately prior to bicycling and after 5 min of exercise.
Growth hormone and prolactin secretion in liver cirrhosis: evidence for dopaminergic dysfunction
Authors: Borzio Mauro , Caldara Roberto , Ferrari Carlo , Barbieri Cristiano , Borzio Franco , Romussi Mario
Published: December 2008

Increased serum growth hormone (GH) and prolactin (Prl) levels and abnormal responses to some stimuli have been reported in patients with chronic liver disease. Serum GH and Prl concentrations were measured in 11 cirrhotic patients and in sex and age matched healthy controls in basal conditions and after administration of L-dopa alone (500 mg), and L-dopa (100 mg) with carbidopa (35 mg) following pre-treatment with carbidopa (50 mg every 6 h for one day), a regimen which results in selective activation of brain dopaminergic pathways. Basal GH and Prl levels were significantly higher in cirrhotics than in controls; serum GH did not increase significantly and serum Prl was subnormally inhibited in patients after both tests. A patient with clearcut hyperprolactinaemia unresponsive to dopaminergic stimulation showed normal basal Prl levels and suppression by L-dopa following clinical improvement, while her elevated GH levels remained unchanged and did not increase after L-dopa.

These data confirm the existence of abnormalities in the regulation of GH and Prl release in liver cirrhosis and suggest that dopaminergic dysfunction may be responsible. The subnormal Prl suppression induced by L-dopa, which stimulates both brain and peripheral dopaminergic receptors, suggests that dopaminergic dysfunction is not confined to the central nervous system in liver cirrhosis. It appears that serum Prl concentration may be of value in monitoring decompensated liver disease and that abnormalities of Prl secretion are reversible with clinical improvement.
Serum 3'-monoiodothyronine levels in normal subjects and in patients with thyroid and non-thyroid disease
Authors: Kirkegaard C. , Faber J. , Cohn D. , Kølendorf K. , Thomsen H. Francis , Lumholtz I. B. , Siersbæk-Nielsen K. , Friis Th.
Published: December 2008

Serum 3'-monoiodothyronine (3'-T1) levels were estimated by means of a specific radioimmunoassay (RIA) preceded by an ethanol extraction. The recovery of 3'-T1 was in mean (± sem) 110 ± 9%, and the lower detection limit was 23 pmol/l. Serum levels of 3'-T1 in 34 euthyroid healthy subjects were (median (range)) 55 pmol/l (<23-168 pmol/l), in 13 hyperthyroid patients 133 pmol/l (70-265 pmol/l) (P < 0.01) and in 13 hypothyroid patients <23 pmol/l (<23-68 pmol/l) (P <0.01). In 11 patients with chronic renal failure serum 3'-T1 levels were highly increased 285 pmol/l (115-1538 pmol/l) (P < 0.01) and correlated inversely to creatinine clearance (R = −0.68, P < 0.05). In patients with liver cirrhosis serum 3'-T1 levels were unaffected, whereas in 19 patients with endogenous depression studied before and after recovery from the depression serum levels decreased from 70 pmol/l (< 23-248 pmol/l) to 30 pmol/l (<23-95 pmol/l (P < 0.01). Administration of propranolol 40 mg b. i. d. for 2 weeks did not affect serum 3'-T1 levels. The study shows that 3'-T1 is present in serum from euthyroid man and varies with thyroid function. Further, it is suggested that 3'-T1 in contrast to other iodothyronines primarily is eliminated by the kidneys.
Effect of cycloheximide on iodothyronine formation in vitro
Authors: Inoue K. , Okamura K. , Shiroozu A. , Nakashima T. , Yoshinari M.
Published: December 2008

The unique inhibitory effect of cycloheximide (CH) on the coupling of iodotyrosines was examined in vitro. Rat thyroid lobes were incubated for 8 h under our improved condition. In the presence of 10−4-10−3 m CH, the per cent uptake of 131I decreased, proportionate synthesis of [131I]MIT increased slightly, and that of [131I]T4 or [131I]T3 decreased markedly. The incorporation of medium 127I into T4 or T3 during the 8 h incubation period decreased markedly, but was fairly constant into MIT and only slightly decreased into DIT. Thus the inhibitory effect of CH seemed more prominent on iodothyronine formation than on iodotyrosine formation in this in vitro system. Inhibition of formation of newly labelled iodothyronines seemed to occur almost in parallel with the inhibition of [3H]amino acid incorporation into the thyroidal soluble protein. However, the coupling of iodotyrosines prelabelled in the absence of CH did not seem to be affected by CH. The presence of 10−4 m CH induced the Wolff-Chaikoff effect at a lower iodide concentration than that which occurred in the absence of CH, suggesting that CH sensitized the Wolff-Chaikoff effect. However, the organification of 127I and T4 synthesis were markedly reduced in the presence of CH even before the apparent Wolff-Chaikoff effect was initiated. These results give further support to our contention that prethyroglobulin is more important for organification of iodide than pre-existing thyroglobulin. We conclude that CH reduces coupling efficiency indirectly, probably by inhibiting the formation of prethyroglobulin with a favourable structure for coupling.