bluuebunny/crossref_metadata_2025 huggingface dataset:
Benserazide, a stimulator of prolactin release: a new test in the diagnosis of pituitary prolactin-secreting tumours
Authors: Pontiroli A. E. , Falsetti L. , Voltolini A. M. , Alberetto M. , Pellicciotta G. , de Pasqua A. , Girardi A. M. , Pozza G.
Published: December 2008

Benserazide, an extra-cerebral inhibitor of dopa-decarboxylase, elicits prolactin (Prl) release in normal subjects when administered po. The aims of this study were to characterize the effect of benserazide on Prl release and to evaluate benserazide as a diagnostic tool in hyperprolactinaemic patients. In normal subjects, the effect of 50 mg benserazide is reduced to a greater extent by 500 mg than by 200 mg 1-dopa, and is nullified by dopamine (DA, 50 mg iv in 180 min), which also decreases fasting plasma Prl levels. Doses of 25, 50 and 150 mg benserazide elicit Prl responses which are slightly and progressively but not significantly higher; a second dose of 50 mg, administered 150 min later, is without effect on Prl release, while TRH (200 μg iv) elicits a further Prl peak. Since it is known that consecutive doses of TRH yield progressively lower Prl responses while 5-hydroxytryptophan (the precursor of serotonin) further increases Prl release in response to benserazide, we hypothesize that, in an area involving both the hypothalamus and the pituitary gland, anti-DA drugs (benserazide), TRH, and serotonin stimulate Prl release by interacting with different kinds of receptors.

When administered to hyperprolactinaemic patients, benserazide stimulated Prl release in puerperal women and in patients with functional hyperprolactinaemias, but was totally ineffective in patients with pituitary adenomas, whatever the fasting plasma Prl levels.

In 2 patients with a normal sellar tomography in whom benserazide induced no Prl release, a second tomography or computerized axial tomography of the brain, performed respectively 3 and 6 months later, revealed a pituitary microadenoma. These results suggest that benserazide may be a valuable diagnostic tool in the differential diagnosis of hyperprolactinaemia.
Growth hormone and prolactin secretion by dispersed cell cultures of a normal human pituitary: effects of thyrotrophin releasing hormone, theophylline, somatostatin, and 2-bromo-α-ergocryptine
Authors: Adams Eric F. , Brajkovich Imperia E. , Mashiter Keith
Published: December 2008

Growth hormone (GH) and prolactin (Prl) secretion by a normal human pituitary in dispersed cell culture has been investigated. Prl secretion was significantly stimulated after 0.5, 1,2 and 4 h exposure to 1, 10, 100 and 1000 ng/ml thyrotrophin releasing hormone (TRH). Maximal effects were obtained with 10 ng/ml TRH at 2 h, higher doses being less effective. GH secretion was unchanged with the exception that 1 ng/ml TRH produced a small decrease at 4 h. GH and Prl secretion was significantly inhibited by incubation with 0.01, 0.1, 1 or 10 μg/ml 2-bromo-α-ergocryptine (bromocriptine). The inhibition persited for a further 24 h after removal of bromocriptine. Theophylline (10−2 m) significantly increased GH and Prl secretion during a 4 h incubation and this effect was blocked by co-incubation with 10 ng/ml somatostatin (SRIF). SRIF also inhibited basal GH and Prl secretion during 4 h and removal of SRIF and incubation for at further 4 h led to a rebound in GH and Prl secretion to levels greater than control.

It is concluded that cell culture techniques previously applied to the study of hormone secretion by pituitary adenomas can be equally applied to the normal human pituitary.
Effect of goitrogen administration on the circadian rhythm of serum thyroid stimulating hormone in the rat
Authors: Stringer B. , Wynford-Thomas D. , Jasani B. , Williams E. D.
Published: December 2008

Adult male rats were fed a goitrogen, aminotriazole, for 74 days at a dose known to suppress thyroid function completely. At the end of this period, these animals along with matched controls were killed in groups of seven at 3 hourly intervals throughout a 24 hour period, and serum TSH, T3, T4 and albumin assayed.

No significant circadian rhythms of T3, T4 or albumin were found in either, but a highly significant rhythm of TSH was demonstrated both in controls and goitrogen treated groups, with a diminished relative amplitude in the latter.

The results indicate that a significant diurnal rhythm of serum TSH persists in the rat despite long-term blockade of thyroid hormone synthesis and that the existence of this rhythm is therefore independent of the presence of circulating T3 or T4.
Follow-up of women with large-for-dates infants. Early insulin and C-peptide response to intravenous glucose, blood lipids and HLA-types
Authors: Persson B. , Möller E. , Thunell S.
Published: December 2008

In a previous study we determined the glucose disappearance rate (kt) in 129 newborn large-for-dates infants (LFD) born to mothers without known diabetes. Twenty-six infants (i.e. 20.6%) had elevated kt values similar to those in offspring of diabetic mothers. A follow-up study of 123 of these mothers was performed 7 years after delivery and included determination of early insulin and C-peptide response to intravenous glucose, plasma concentrations of 3-hydroxybutyrate, cholesterol, triglycerides, lipoproteins and HLA-typing. Two subjects had developed diabetes and altogether 14% had a kt below 1.0. Measures of the early insulin and C-peptide response to glucose were equally well correlated to maternal kt values (r = 0.40, P < 0.001). Measures of the early insulin and C-peptide responses were significantly correlated (r = 0.64, P < 0.001). The frequency distribution of HLA antigens were not different from normal and there was no association between HLA-B8 or B15 and impaired insulin response or glucose tolerance. Multiple regression and discriminate analysis of clinical and biochemical variables could not accurately identify women with high or low kt values. Multiple regression analysis using infant kt value as the dependent variable disclosed only a weak, but significant, inverse association to maternal insulin response to glucose at follow-up.
Free norethisterone as reflected by saliva concentrations of norethisterone during oral contraceptive use
Authors: Odlind Viveca , Johansson Elof D. B.
Published: December 2008

Saliva and plasma concentrations of norethisterone (NET) were determined by a radioimmunoassay in 5 healthy women and in one epileptic woman on phenytoin treatment during a 21-day cycle on an oral contraceptive containing 3 mg NET-acetate and 0.05 mg ethinyloestradiol. Plasma non-protein bound concentrations of NET were determined by equilibrium dialysis. Sex hormone binding globulin (SHBG) was measured in all samples. An excellent correlation was found between plasma total, plasma non-protein bound and saliva levels of NET. Plasma non-protein bound and saliva concentrations were in the same range throughout, indicating that saliva concentrations reflect the free fraction of NET in plasma. SHBG increased considerably in all women. A slight decrease in the ratio between total and non-protein bound concentrations was found with time, possibly reflecting a slight increase in protein binding with increasing SHBG. The woman on anticonvulsant therapy had plasma total, plasma unbound and saliva NET concentrations that were only 30 per cent of those of the healthy women. The relationship between the different fractions was similar to that found in the healthy women. The non-protein bound fraction of NET was 4–5 per cent of the total in all women studied.
Human thyroid blood flow response to endogenous, exogenous human, and bovine thyrotrophin measured by electromagnetic flowmetry
Authors: Tegler Lennart , Gillquist Jan , Anderberg Bo , Jacobson Gunilla , Lundström Björn , Roos Paul
Published: December 2008

Human thyroid blood flow (TBF) was studied with electromagnetic flowmetry during operation. Measurements were made of the effect on TBF of injections of bovine TSH into one inferior thyroid artery in 6 patients; 6 other patients were given human TSH, and in 10 patients measurements were made both of TBF and endogenous TSH released after administration of TRH in a peripheral vein.

The TBF increased after all three types of injection. The mean of the TBF maxima after bovine TSH was 2.26 ± 0.35 (mean ± sem) relative to basal TBF, after human TSH 1.97 ± 0.28, and after TRH 1.64 ± 0.20. In the three groups combined it was 1.92 ± 0.16. The TBF was often increased already during the first recording period 1–10 min after TSH or TRH administration. The mean TBF was approximately doubled at 30–50 min. There were considerable inter-individual variations in the latent time and maximum response of TBF, especially after human TSH, but we found no correlation between the response and the TSH serum concentration in any group.

A prompt, but inter-individually varying, increase in TBF was confirmed. This increase is suggested to be secondary to an increased intrafollicular metabolic activity and not primarily regulating the thyroid function.
Heterogeneity of somatostatin like immunoreactivity (SLI) in extracts of porcine, canine and human pancreas
Authors: Newgard Christopher B. , Holst Jens J.
Published: December 2008

Four different extraction procedure representative of methods commonly employed in the isolation of somatostatin like immunoreactivity (SLI) were tested for their ability to extract large MW forms of SLI from porcine, canine and human pancreas. The yield of SLI and recovery of added somatostatin was much higher with methods involving traditional acid/ethanol extraction (methods I and II) than with methods involving boiling of tissues in water or 2 m CH3COOH (methods III and IV). Porcine and canine pancreases extracted by methods III and IV (but not methods I and II) revealed remarkable molecular heterogeneity upon gel filtration, but immuno-affinity-chromatography eliminated the largest forms. A component of approximately 3000 daltons was immunoabsorbable and resisted refiltration in 8 m urea. No large forms were detectable in human pancreases. The SLI peaks eluting at the position of synthetic somatostatin could be resolved into two components, one of which was lacking C-terminal immunoreactivity. It is concluded that the method of extraction as well as the species investigated and the specificity of the antisera employed will influence significantly the results of studies of the tissue forms of somatostatin.
The recovery of the hypothalamo-pituitary-ad renal axis after transsphenoidal operation in three patients with Cushing's disease. The effect of prior external pituitary irradiation
Authors: Lamberts Steven W.J. , Klijn Jan G. M. , de Jong Frank H. , Birkenhäger Jan C.
Published: December 2008

The recovery of the hypothalamo-pituitary-adrenal axis after selective transsphenoidal adenomectomy was studied in 3 patients with Cushing's disease by measuring basal plasma ACTH and cortisol concentrations, cortisol secretion rate, the diurnal rhythm of cortisol, and the reaction of cortisol to lysine vasopressin (LVP), of compound S to metyrapone and of cortisol and growth hormone to an insulin-induced hypoglycaemia. The third patient had been treated previously by external pituitary irradiation. In 2 patients basal plasma ACTH levels returned within normal values before plasma cortisol, but no supra-physiological plasma concentrations of ACTH were seen as has been observed after withdrawal of exogenous glucocorticoids. With regard to the different stimulation tests: at first the normal reaction of plasma cortisol to LVP returned after 3 months, at the same time as the restoration of growth hormone secretion in response to hypoglycaemia. A normalization of the reaction to metyrapone was seen thereafter while finally the reaction of cortisol to an insulin-induced hypoglycaemia and the diurnal rhythm of plasma cortisol returned 15 to 18 months after operation in the first patient and after 12 months in the second patient. Selective adenomectomy had also been carried out in the third patient, as evidenced by normal TSH, LH and FSH secretion. Hypocortisolism, and a deficient ACTH and growth hormone secretion in response to the stimuli mentioned, however, did not normalize up till 22 months after operation. The restoration of the hypothalamo-pituitary-adrenal axis after selective pituitary adenomectomy in Cushing's disease was prevented in this patient by prior external pituitary irradiation.
Influence of medroxyprogesterone acetate (Provera) on plasma growth hormone levels and on carbohydrate metabolism
Authors: Eigenmann J. E. , Eigenmann R. Y
Published: December 2008

The combined effects of oestradiol and medroxyprogesterone acetate on growth hormone (GH) levels and carbohydrate metabolism were studied in 6 ovariohysterectomized dogs, which previously had shown moderate increments in GH after medroxyprogesterone acetate (MPA) administration. Oestradiol (Oe2) implants were administered 5 months after the last MPA injection, when MPA and GH levels tended to decrease. Following Oe2 administration GH levels rose significantly. Single MPA injections (100 mg) given 20 days after Oe2-priming were followed by still further increased GH levels. These GH levels were several-fold higher than GH levels achieved by previous MPA administration alone. GH levels decreased in 3 dogs after 35 days and remained elevated in the other 3 dogs as long as 70 days after MPA administration with Oe2 priming. Glucose assimilation became impaired and insulin response to a glucose load increased in relation to elevated GH levels. Oe2-primed control dogs, which received no MPA, failed to develop elevated GH levels.

These findings indicate (1) that Oe2 and MPA induce overproduction in ovariohysterectomized dogs synergistically (2) that GH levels of the magnitude evoked are associated with glucose intolerance and insulin resistance.
Distribution of oestrogen-induced peroxidase in the rat uterus
Authors: Affleck A. , Keeping H. S. , Newcombe A. M. , Jellinck P. H.
Published: December 2008

The activity of oestrogen-induced peroxidase in sections along the uterus of normal and mammary tumour-bearing adult rats was measured. Oestradiol increased the activity of this enzyme in the cervix as well as in other parts of the uterus in ovariectomized or immature rats. Peroxidase activity per mg protein was twice as high in the cervix as in the rest of the uterus where it was evenly distributed along both horns. The concentrations of oestrogen receptors in the cytosol and nucleus in each uterine horn and in the cervix was also determined and found to be lower in the cervix than in other sections of the uterus.
Comparison of acute effects of 1.25- and 24.25-dihydroxy-vitamin D3 in normal subjects
Authors: Heynen G. , Cornet F. , Franchimont P. , Gaspar S. , Plomteux G. , Cession-Fossion G. , Russel R. G. G. , Kanis J. A.
Published: December 2008

Effects of small iv doses of 1.25-dihydroxy-and 24.25-dihydroxy-vitamin D3 (1 μg) were studied in 10 normal subjects. Injection of 1.25 (OH)2D3 was associated with small but significant increases in plasma calcium and phosphate but plasma levels of immunoreactive parathyroid hormone (iPTH) and calcitonin (iCT) did not change. The administration of 24.25 (OH)2D3 was associated with comparable increases in plasma calcium and a small and transient decrease in plasma iPTH. Plasma levels of iCT did not change. 24.25 (OH)2D3 also significantly increased glomerular filtration rate and decreased the urinary excretion of noradrenaline, in contrast to 1.25 (OH)2D3 which had no effect on these variables. The rapid infusion of calcium significantly decreased levels of iPTH. We conclude that small doses of 1.25 (OH)2D3 and 24.25 (OH)2D3 have little, if any, direct effect on the secretion of PTH and CT in man.
Effect of 2-substituted oestrogens in vivo on the metabolism of noradrenaline in rat brain
Authors: Köster G. , Breuer H. , Schneider H. Th.
Published: December 2008

The effects of oestradiol-17β, 2-hydroxyoestradiol-17β and 2-methoxyoestradiol-17β on the metabolism of [3H]noradrenaline were studied in various brain regions of ovariectomized rats in vivo. Under the experimental conditions chosen, oestradiol-17β had no effect on the metabolic pattern of noradrenaline. After pre-treatment of ovariectomized rats with 2-hydroxyoestradiol-17β, the formation of methylated metabolites of noradrenaline (normetanephrine and 3-methoxy-4-hydroxyphenylglycol sulphate) was reduced, whereas that of non-methylated products (3,4-dihydroxymandelic acid and 3,4-dihydroxyphenylglycol sulphate) was increased. The inhibition of methylation was most pronounced in posterior hypothalamus and less significant in anterior hypothalamus and thalamus. Pre-treatment with 2-methoxyoestradiol-17β yielded inconsistent results. From the findings described here it may be concluded that 2-hydroxyoestradiol-17β, as previously shown in vitro, also affects the metabolism of noradrenaline in vivo by directly interacting with the catechol-O-methyltransferase. It is suggested that this metabolic effect may be responsible - at least to some extent - for the inhibitory effect of 2-hydroxyoestradiol-17β on LH secretion.
Increase in sleep related GH and Prl secretion after chronic arginine aspartate administration in man
Authors: Besset A. , Bonardet A. , Rondouin G. , Descomps B. , Passouant P.
Published: December 2008

Arginine aspartate was administered orally (250 mg/kg/day) for one week to 5 healthy male human volunteers aged 20–35. After this period, the 24 h patterns of growth hormone (GH) and prolactin (Prl) secretion were determined by radioimmunoassay on blood samples withdrawn every 20 min and correlated with the polygraphic recordings of electroencephalogram, electromyogram and electrooculogram. The results were compared to data obtained in identical conditions with the same subjects but after a week of placebo administration.

In all 5 subjects the slow wave sleep related GH peak was about 60% higher after a week of arginine aspartate administration than in the control period, with individual changes of + 24, + 25, + 42, + 47 and + 162%.

The nocturnal mean plasma Prl of each subject was higher after arginine aspartate than before. The nocturnal rise of plasma Prl increased from a mean value of + 21.5% during the placebo period to + 95% at the end of the arginine aspartate treatment.

These hormonal modifications were not accompanied by any detectable alteration of sleep organization and specially of the slow wave sleep pattern, suggesting a direct neuroendocrine action of the drug.
Pattern of prolactin secretion and pituitary responsiveness to LRH in pseudopregnant rats maintained in constant light
Authors: Koiter T. R , van der Gugten A. A. , Pols-Valkhof N. , van Eekeren J. , Schuiling G. A.
Published: December 2008

Secretion of LH in response to an LRH infusion (104 ng/h during 21 h), secretion of progesterone (P) and 20 α-dihydroprogesterone (DHP), as well as the 24 h rhythm of prolactin (Prl) secretion were investigated in rats rendered persistently oestrous by exposure to constant light and in which subsequently pseudopregnancy (PSP) had been induced by cervical stimulation after induction of ovulation by hCG. Similar persistently oestrous rats, but otherwise untreated, served as controls.

LRH was infused through an intra-jugular cannula and blood samples for assay of LH were taken via an intra-carotid cannula. LH responses were judged on the basis of the mean maximal height (MH; ng LH ml plasma) and the rate of decrease or half life (t½ of the plasma LH concentrations after 2 h of LRH infusion. For assay of P and DHP blood samples were taken from the orbitalplexus. In another series of animals blood, for assay of Prl, was sampled every 2 h for 24 h from a cannula with the tip in the right atrium.

It was observed that in persistently oestrous rats LH-responses were high (MH = 3326 ± 305) and steep (t½ = 65 ± 10 min). On the day after the night of ovulation (day 0 of PSP) and on days 1, 5 and 9 of PSP the responses were lower (MH between 1315 and 1041) and more blunted (t½ varied between 236 and 142 min), whilst on day 12 of PSP they were again higher (MH = 4416 ± 575) and steeper (t½ = 101 ± 12 min).

P and DHP concentrations were low in persistently oestrous rats and high during days 5 and 8 of PSP. On day 12 of PSP P concentrations were low again, while the DHP concentrations had increased further.

In persistently oestrous rats the plasma Prl levels were low with incidental elevations (up to 141 ng Prl/ml aAntoni van Leeuwenhoekhuis The Netherlands Cancer Institute, Amsterdam, The Netherlands plasma). During days 8 – 9 of PSP Prl was secreted at irregular intervals (1 to 3 peaks/24 h) with peak levels of up to 400 ng Prl/ml plasma. On days 11 – 12 of PSP, Prl peaks were lacking almost completely: only a few minor elevations (up to 41 ng Prl/ml plasma) were measured.

It is concluded that during days 0 to 10 of pseudopregnancy under constant light the endocrine state of the animals (in terms of LRH-responsiveness and P and DHP secretion) differs significantly form that during the previous and the following days. As similar changes are observed in PSP rats maintained under standard lighting conditions, it is apparent that the lighting conditions do not influence these changes. The pattern of Prl secretion during PSP, on the other hand is affected by the lighting conditions.
Inhibition of leukocyte migration by human thyroid adenocarcinoma associated antigens
Authors: Aoki Norihiko , DeGroot Leslie J.
Published: December 2008

The agarose microdroplet leukocyte migration inhibition (LMI) assay was used successfully to demonstrate the existence of cell-mediated immunity to tumour-associated antigens (TAA) in patients with thyroid adenocarcinoma. With the use of crude tumour extracts obtained from a mixed papillary-follicular adenocarcinoma of the thyroid by hypertonic KCl solubilization, 50.0% positive reactivity was observed in metastatic thyroid cancer patients, whereas no healthy donors or patients with auto-immune thyroid disease showed a positive response in the LMI assay. Among responders, no antigenic cross-reactivity was found between the crude tumour extracts and non-cancerous antigens such as human thyroglobulin, or extracts of Graves' disease thyroid tissue, or kidney tissue. The crude tumour extracts were fractionated by Sephadex G-200 chromatography and the effluent materials were pooled into three fractions. The high molecular weight fraction corresponding to the side of thyroglobulin elution, and the intermediate molecular weight fraction, showed no TAA activity. The low molecular weight fraction including substances of molecular size near that of ovalbumin (45 000 molecular weight) selectively retained the TAA activity. TAA activity in the low molecular weight fraction was concentrated in comparison to the crude tumour extracts. When this fraction was tested in the LMI assay, positive reactivity increased in metastatic thyroid cancer patients, but no response was observed in either healthy donors or patients with thyroid auto-immune diseases. The LMI response to TAA was more striking in patients with active metastatic cancer than in those whose metastatic foci had responded to treatment.
A study of Δ5-3β-hydroxysteroid dehydrogenase in human foetal adrenal glands
Authors: Hirato Kumiko , Yanaihara Takumi , Nakayama Tetsuya
Published: December 2008

'Microsomal fractions' of foetal adrenal tissue obtained at 18–24 weeks of gestation were incubated with several radioactive Δ5-3β-hydroxysteroids to study the properties of Δ5-3β-hydroxysteroid dehydrogenase (Δ5-3β-HSD)1. Incubations were performed under CO gas to inhibit hydroxylation. Enzyme activity was measured by the conversion of pregnenolone, 17α-OH-pregnenolone, dehydroepiandrosterone, androstenediol and androstenetriol to the corresponding Δ4-3-oxo-steroids. 17α-OH-pregnenolone was the most preferred substrate for the enzyme among the Δ5-3β-substra-teroid substrates examined. Michaelis constants (Km) of Δ5-3β-HSD were 2 × 10−4 m for pregnenolone, 7.2 × 10−6m for 17α-OH-pregnenolone and 7.8 × 10−6 m for dehydroepiandrosterone. No significant amounts of Δ4-3-oxosteroids were produced from androstenediol and androstenetriol, and Km values for them were not determined. The enzyme preferred NAD+ to NADP+ as a hydrogen receptor and the Km for NAD+ was 1.1 × 10−4 m in the presence of 17α-OH-pregnenolone. The enzyme activity for 17α-OH-pregnenolone was competitively inhibited by dehydroepiandrosterone, suggesting that both Δ5-3βhydroxysteroids were catalyzed at the same site of the enzyme, and also non-competitively by oestriol. Other steroids produced by the foeto-placental unit which inhibited the enzyme activity for 17α-OH-pregnenolone were pregnenolone-3β-yl-sulphate, androstenediol, oestradiol17β, oestrone and oestradiol-17β-yl-sulphate. It appears likely that the formation of Δ4-3-oxo-steroids as precursors for cortisol synthesis in foetal adrenal glands is influenced by the presence of steroids produced by the foeto-placental unit.
Effect of insulin and epinephrine on some early oestrogenic responses in the rat uterus
Authors: Steinsapir J. , Rojas A. M. , Alarcón O. , Tchernitchin A. N.
Published: December 2008

Oestradiol induces uterine eosinophilia and oedema, both in the intact immature rat and in the adult ovariectomized rat. These responses are decreased in ovariectomized-adrenalectomized adult rats, in adrenalectomized immature rats and in medullectomized immature rats. Pre-treatment with L-epinephrine restored both oestrogenic effects.

Insulin inhibits oestrogen binding by uterine eosinophils and concurrently decreases oestrogen-induced uterine oedema and eosinophilia. These phenomena do not occur with inactive insulin. Insulin also induces blood eosinopaenia, suggesting an explanation for the findings in the uterus.
Is 3α-androstanediol a marker of peripheral hirsutism?
Authors: Toscano Vincenzo , Sciarra Francesco , Adamo Maria Vittoria , Petrangeli Elisa , Foli Sonia , Caiola Stefania , Conti Carlo
Published: December 2008

The behaviour of 5α-reduced metabolites of testosterone, dihydrotestosterone1, 3α-androstanediol and 3β-androstanediol, was studied in 36 hirsute women: Group I: 24 patients with high plasma levels of testosterone, androstenedione and/or dehydroepiandrosterone sulphate and Group II: 12 patients with normal plasma concentrations of these steroids.

Testosterone and its 5α-reduced metabolites were determined by radioimmunoassay after chromatographic separation on celite 535 microcolumns.

Plasma 3α-androstanediol was found to be elevated both in Group I (26.9 ± 10.8 sd ng/100 ml) and in Group II patients (23.2 ± 10.5 sd ng/100 ml). 3β-Androstanediol and dihydrotestosterone, on the contrary, were elevated in only a few cases: in 6 cases in Group I and in 2 and in 1 case, respectively, in Group II.

The finding of high plasma 3α-androstanediol levels in hirsute women, with normal values of the other androgens, may be an index of hirsutism of peripheral origin, since this steroid is produced almost exclusively in the extraglandular compartment.
Comparison of radioimmunoassay, chemical assay (HPLC) and bioassay for arginine vasopressin in synthetic standards and posterior pituitary tissue
Authors: Möhring J. , Böhlen P. , Schoun J. , Mellet M. , Süss U. , Schmidt M. , Pliška V.
Published: December 2008

Radioimmunoassay and chemical assay (high performance liquid chromatography (HPLC) with fluorescence detection) for arginine vasopressin (AVP) in purified synthetic preparations and in posterior lobe tissue samples (ox and rat) yielded essentially identical values. In tissue samples from the neurohypophysis, the reproducibility of the former method was roughly twice as good. The routinely used blood pressure bioassay was very poorly reproducible and yielded values deviating from the two other methods. In all three assays, the coefficient of variation was roughly five times higher in tissue samples than in synthetic preparations. It is suggested that a chemical rather than a biological assay is used for standardization of AVP for radioimmunoassay. Large differences were found in the quality of AVP preparations potentially usable as standards and tracers (after iodination) for radioimmunoassay. All commercial preparations should therefore be checked for their AVP and impurity content by high performance liquid chromatography.
A prospective study of the differential changes in serum thyroglobulin and its autoantibodies during propylthiouracil or radioiodine therapy of patients with Graves' disease
Authors: Feldt-Rasmussen Ulla , Bech Karine , Date John , Petersen Per Hyltoft , Johansen Klaus
Published: December 2008

Measurement of serum thyroglobulin (Tg) and its autoantibody (TgAb) by radioimmunological methods was performed in 48 patients with Graves' disease during treatment with radioiodine (n = 16) or propylthiouracil (PTU) (n = 32).

Twenty-five of the 48 patients were TgAb positive, their sera being inaccessible to measurement of serum Tg. TgAb showed only minor changes during PTU treatment, whereas TgAb fell rapidly after radioiodine, in 5 of 16 patients to unmeasurable levels, followed by a secondary rise to 4.5 times pre-treatment level after 20 weeks.

Serum Tg showed a steady increase during the first weeks after radioiodine treatment, but fell to lower levels after one year. PTU caused only minor changes in the serum Tg concentration. There was no shift in molecular sizes of either Tg or TgAb during the course of the treatments.

Five of 16 131I-treated patients developed myxoedema, 4 of whom were TgAb positive. Another 3 patients had high increases in TgAb without myxoedema.

Six of 18 patients had relapse of thyrotoxicosis after withdrawal of PTU-treatment. There was no significant difference in serum concentrations of TgAb or Tg between those developing relapse and those remaining in remission, and it is concluded that serum Tg is a poor predictor of relapse in medically treated thyrotoxicosis.
Factors influencing the release of cyclic AMP from mouse thyroid tissue stimulated by TSH in vitro
Authors: Gustafson Asa , Ahrén Bo , Hedner Pavo , Nilsson Hans
Published: December 2008

The accumulation of cyclic AMP (cAMP) in mouse thyroid tissue in response to TSH in the presence of 1 mm theophylline was accompanied by a release of the nucleotide from the tissue into the incubation medium. This cAMP release was almost rectilinearly related to the time of exposure to TSH, and rectilinearly related to the log concentration of TSH in the range 0.1–5 mU/ml. The cAMP release proved to be independent of the pre-incubation time up to 4 h, and took place also in the absence of methylxanthines when the cAMP level was low. The total cAMP accumulation in response to TSH was augmented by different inhibitors of protein synthesis but the fraction of the nucleotide that was retained intracellularly was increased only by puromycin. Dipyridamole had an effect similar to that of puromycin. Depolarization or treatment with ouabain did not change the distribution of cAMP between tissue and medium.

It is concluded that the release of cAMP from thyroid tissue stimulated by TSH may take place under physiological conditions, that it seems to be regulated by the actual concentration of TSH, and that it may be of significance for the regulation of the intracellular cAMP level.
Insulin releasing action of 2-[2-(4,5-dihydro-1H-imadazol-2-yl)-1-phenylethyl] pyridine dihydrochloride sesquihydrate (DG-5128), a new, orally effective hypoglycaemic agent
Authors: Kameda Kin-ya , Ono Shin-etsu , Koyama Isao , Abiko Yasushi
Published: December 2008

2-[2-(4,5-dihydro-1H-imidazol-2-yl)-1-phenyl-ethyl] pyridine dihydrochloride sesquihydrate (DG-5128) is a new orally effective hypoglycaemic agent structurally unrelated to the known hypoglycaemics. DG-5128 was found to decrease blood glucose levels by stimulating insulin release, like the sulphonylurea hypoglycaemics. However, the study with the rat Langerhans islets in vitro indicated a great difference in mode of stimulation of insulin release between DG-5128 and a sulphonylurea hypoglycaemic, tolbutamide. DG-5128 significantly reversed α-adrenergic inhibition of the glucose-primed insulin release from the islets, while tolbutamide did not. From the comparison with the effects of phentolamine, yohimbine and prazosine, DG-5128 was strongly suggested to stimulate the glucose-primed insulin release through antagonizing at α2-adrenoreceptors on the B cells.
Development of the gonadotrophic resistant ovary syndrome in myasthenia gravis: suggestion of similar autoimmune mechanisms
Authors: Escobar María Eugenia , Cigorraga Selva B. , Chiauzzi Violeta A. , Charreau Eduardo H. , Rivarola Marco A.
Published: December 2008

A woman with myasthenia gravis who developed hypergonadotrophic amenorrhoea was studied. This patient fulfilled all accepted criteria for the diagnosis of the gonadotrophin resistant ovary syndrome: high levels of serum LH and FSH by radioimmunoassay and urinary gonadotrophin excretion by bioassay, low serum oestradiol, lack of response to exogenous gonadotrophin and ovaries with multiple non-stimulated primordial follicles.

The serum of this patient contained a substance which behaving like a gamma globulin, inhibited FSH specific binding to receptors in an in vitro system. This inhibitor was looked for in further patients with hypergonadotrophic amenorrhoea, other immunological diseases or myasthenia gravis with normal menses. Ovarian biopsy was not available in these patients. In all except one who also had the association of myasthenia gravis and hypergonadotrophic amenorrhoea, the inhibitor was not detected.

It is suggested that development of antibodies directed against gonadotrophin receptors or a receptor related membrane domain may play a role in the mechanism of failure of gonadotrophin stimulation in some patients with the gonadotrophin resistant ovary syndrome.
Effects of antibodies to catecholoestrogens and catecholoestrogen methyl ethers on PMS induced ovulations in immature rats
Authors: Ball Peter , Schwarzlose Christian , Emons Günter
Published: December 2008

Endogenously formed catecholoestrogens or their monomethyl ethers were neutralized in the circulation using antisera with high affinity and specificity for 2-hydroxyoestrone and 2-hydroxyoestradiol or 4-hydroxyoestrone and 4-hydroxyoestradiol or the respective methyl ethers in PMS treated immature female rats.

The experimental arrangement used was valid as 1) animals treated with PMS and antiserum to oestrone and oestradiol failed to ovulate without impairment of body weight, 2) ovulations could be restored by injections of hCG at the time when rats treated with PMS alone had their ovulatory LH surge and 3) normal rabbit serum had no effect on ovulations and on body weight.

Treatment of the animals with antisera to catecholoestrogens or their methyl ethers had no negative effect on ovulation frequency, number and shape of ova and body weight, although the doses of antisera used — as calculated from the number of antibody binding sites and affinity constants — must have been more than sufficient to neutralize catecholoestrogens or their methyl ethers in the blood stream. In animals treated with PMS and a blocking dose of antiserum to oestrone and oestradiol ovulations could be restored by injections of 4-hydroxyoestradiol-dibenzoate following a regimen which procured plasma levels of 4-hydroxyoestradiol imitating the concentration/time course of endogenous oestradiol in animals treated with PMS alone.

We conclude that catecholoestrogens and their methyl ethers formed peripherally, are not of crucial importance for ovulation — at least in this model. 4-Hydroxyoestradiol, however, can completely replace the peripheral and physiologically essential oestradiol at central target sites when this primary oestrogen is neutralized by antibodies.
Effects of orchidectomy and sex steroids on vasopressin response to dehydration
Authors: Valiquette G. , Martini L.
Published: December 2008

The secretion of vasopressin has been shown recently to be influenced by gonadal steroids. To further evaluate the relevance of sex steroids in the control of vasopressin secretion, the vasopressin response to dehydration has been studied in normal, castrated and sex-steroid treated castrated male rats.

Short-term (3 weeks) castration did not modify the vasopressin response to 48 h of water deprivation. Long-term (10 weeks) castration, on the other hand, consistently reduced the vasopressin response by more than 50%. In both cases, the osmolality was unaffected.

Treatment of long-term castrated rats with testosterone, dihydrotestosterone, or oestradiol increased the vasopressin response to dehydration towards normal control levels. However, only oestradiol could restore it to and beyond normal levels, although all three steroids were given in doses that were equipotent in bringing back to normal the plasma LH levels of the castrated animals.

Angiotensin-II generation may indirectly be augmented by oestradiol treatment and this may account for the effect of oestradiol here reported. No such mechanism, however, may be invoked in the case of androgens; a direct modulatory effect at the hypothalamic level is postulated for explaining their influence on vasopressin secretion.
131I treatment of diffuse and nodular toxic goitre with or without antithyroid agents
Authors: Bliddal Henning , Hansen Jens Mølholm , Rogowski Preben , Johansen Klaus , Friis Thorkild , Siersbæk-Nielsen Kaj
Published: December 2008

The results of 131I treatment in combination with pre- and post-treatment with carbimazole (n = 122) were compared to the results of 131I used as the only antithyroid treatment (n = 203). The two groups of patients were fully comparable in regard to age, size of goitre and time of observation, and the same diagnostic criteria and dosage regimen of 131I were used. The incidence of early myxoedema in patients with diffuse goitre was significantly reduced after combination therapy, 5 per cent, compared to 16 per cent after 131I as the only antithyroid therapy (P < 0.05). The incidence of late myxoedema was 6 per cent in both groups 3 years after the last treatment, and fully compensated myxoedema was found in 13 and 22 per cent (n.s.). No severe acute side effects were observed after 131I therapy in any of the two groups. It is concluded that - in diffuse toxic goitre - a lower early incidence of myxoedema was obtained on the combined regimen because of either a possibly lower absorbed radiation dose or a more fractionate therapy. A major advantage of the combination therapy is also, that the patients are rendered euthyroid shortly after the diagnosis and remain so during the prolonged period of treatment. 131I treatment in combination with carbimazole is advocated in all patients with diffuse and nodular toxic goitre if the patient is above fertile age and thyroidectomy is not indicated.
Inhibition by calcium channel blockers of the glycogenolytic effect of glucagon in perfused rat liver
Authors: Kimura Satoshi , Matsumoto Toshio , Tada Ryoko , Ogata Etsuro , Abe Kaoru
Published: December 2008

Verapamil and diltiazem, calcium channel blockers, inhibited significantly the glucagon-induced glucose output and 45Ca efflux from perfused rat liver at concentrations higher than 50 μm when the perfusate contained calcium. Although the blockers partially interfered with glucagon-induced elevation of cyclic AMP in the tissue, they also inhibited the effects of cyclic AMP. The blockers did not show the inhibitory effects in the absence of perfusate calcium. However, the inhibition of calcium influx into hepatocytes by omission of extracellular calcium or addition of EGTA did not interfere with these effects of glucagon and cyclic AMP. In the presence of extracellular calcium, the blockers did not inhibit cyanide-induced glucose output, indicating that the activity of glycogen phosphorylase and later processes leading to glucose output were not affected by the blockers. These data suggest that, in the presence of calcium, the blockers inhibit the effect of glucagon also at a step (or steps) subsequent to cyclic AMP production and before the activation of phosphorylase b, probably by inhibiting glucagon-induced mobilization of calcium from intracellular calcium pools rather than inhibiting calcium influx into hepatocytes.
46,XX gonadal absence: a variant of the XX pure gonadal dysgenesis?
Authors: Medina Martha , Kofman-Alfaro Susana , Pérez-Palacios Gregorio
Published: December 2008

Two unrelated 46,XX individuals with female phenotype and sexual infantilism were studied. Endocrine findings showed anoestrogenism and hypergonadotrophism with a normal pituitary response to LRH. Laparotomy disclosed ovarian absence with normal Mullerian derivatives and no gonadal streaks were found within the true pelvis or inguinal canals.

This condition represents the 46,XX counterpart of the 46,XY gonadal absence syndrome. Whether the XX agonadism reported here is a different and distinctive entity or is a variant of the XX pure gonadal dysgenesis syndrome can not be ascertained at present.
Danazol has progestin-like actions on the human endometrium
Authors: Kokko E. , Jänne O. , Kauppila A. , Rönnberg L. , Vihko R.
Published: December 2008

The administration of danazol, 200 mg three times daily, from the 3rd to the 23rd day of the cycle to normally menstruating women exhibited the following actions on the human endometrium: significantly reduced cytosol oestrogen and progestin receptor concentrations, and declined 17β-hydroxysteroid dehydrogenase activity. Very similar results were obtained during medroxyprogesterone acetate (100 mg daily) treatment for the same period of time. Danazol administration did not decrease circulating gonadotrophin levels but clearly suppressed luteal serum oestradiol and progesterone concentrations. Danazol was found to bind in vitro to endometrial progestin receptor with an affinity approximately 3% of that of progesterone. These findings are compatible with the notion that a local progestin-like rather than a systemic action of danazol is the way by which its therapeutic effect is exerted. This may be potentiated by the suppression of circulating oestradiol levels.
Identification of somatostatin in the human placenta
Authors: Lee Jau Nan , Wu Ping , Chard Tim
Published: December 2008

High pressure liquid chromatography (HPLC), gel chromatography and radioimmunoassay (RIA) were applied to the identification of cyclic somatostatin in human placental tissue. Methanol extracts of the placenta were treated with acetic acid and chloroform, purified on an octadecylsilane column, fractionated on HPLC and gel filtration, and assessed by RIA. It is concluded that human placental somatostatin is similar or identical to cyclic somatostatin on other tissue.
Effects of oestradiol and levonorgestrel on lipoprotein lipids and postheparin plasma lipase activities in normolipoproteinaemic women
Authors: Tikkanen M. J. , Nikkilä E. A. , Kuusi T. , Sipinen S.
Published: December 2008

The effects of oestradiol and levonorgestrel on plasma lipoprotein cholesterol (Chol) and triglyceride (Tg) levels and on postheparin plasma lipoprotein lipase (LPL) and hepatic lipase (HL) activity were studied in 52 normolipoproteinaemic women. The androgen-derived progestin levonorgestrel increased postheparin plasma hepatic lipase (PH-HL) activity and decreased plasma high-density lipoprotein (HDL) lipid concentrations in a manner opposite to that of oestradiol. The relationships between PH-HL activity and HDL lipids suggest an important role for this enzyme as a mediator of sex hormone action on HDL.
Effect of metoclopramide induced hyperprolactinaemia on the gonadotrophic response to oestradiol and LRH
Authors: Andersen A. Nyboe , Schiøler V. , Hertz J. , Bennett P.
Published: December 2008

The effect of oral metoclopramide 10 mg three times daily during the follicular and periovulatory period on Prl, LH, FSH, oestradiol and progesterone was determined in 6 regularly menstruating women. During a control cycle and a treatment cycle the gonadotrophic response was measured after 1 mg oestradiol benzoate given im on the 8th day and after LRH 25 μg iv on the 8th and 11th day of the menstrual cycle. Prl, LH and FSH were also measured in 7 post-menopausal women either during short-term or long-term treatment with metoclopramide. Compared to a control cycle metoclopramide significantly (P < 0.01) increased serum Prl, but a sustained hyperprolactinaemia was not obtained in 2 women. Treatment significantly (P < 0.02) increased the LH and FSH responses to LRH and augmented the negative feedback of oestradiol on both LH and FSH (P < 0.05). A major gonadotrophin surge occurred in those 2 women where a sustained hyperprolactinaemia was not achieved. Oestradiol benzoate caused a significant increase of the LH (P < 0.01) and FSH (P < 0.05) responses to LRH after 72 h during the control cycle, but failed to increase either LH or FSH responses significantly during treatment. Short-term hyperprolactinaemia in post-menopausal women was not associated with any consistent alteration in either LH or FSH levels or pulsatility, but chronic treatment resulted in a significant reduction in serum FSH (P < 0.02), without any alteration in LH levels or pulsatility. LH and FSH responses to LRH increased in all. There was no effect on serum DHAs, urinary androgens or follicular phase serum progesterone levels.

These data show that moderate drug induced moderate hyperprolactinaemia is associated with an increased responsiveness of both LH and FSH to LRH, and has a more pronounced effect on the negative feedback compared to the positive feedback of oestradiol on gonadotrophin secretion. It is suggested that hypersecretion of Prl impairs periodic LH release, mainly through an altered feedback mechanism, but also has a direct inhibitory effect on FSH secretion.
Age-related changes in the feedback regulation of gonadotrophin secretion in the immature and adult male rabbit
Authors: Berger M. , Jean-Faucher Ch. , De Turckheim M. , Veyssière G. , Jean CI.
Published: December 2008

Male rabbits were castrated at infantile (30 days), peripubertal (60 days) and adult (7–8 months) stages. Two different doses of testosterone were injected 10 days after castration (5 injections at 12 h intervals). Plasma LH and FSH were determined by RIA 1,5 and 10 days after castration and 1 h after the last injection of testosterone. The response of both gonadotrophins to castration was age-dependent. In 30 day old castrated males LH was not significantly modified and FSH had increased only 10 days after castration. In 60 day old and adult males FSH and LH levels were increased 24 h after castration and continued to rise as time progressed. For both gonadotrophins, the response of adult males to castration was higher than that of immature animals. At all stages studied, the highest dose of testosterone (250 μg/kg body weight) depressed post-castration LH and FSH levels. Twenty-five μg of testosterone per kg body weight was effective to depress LH levels only in 30 day old males, suggesting a change in the hypothalamic-pituitary unit to the negative feedback of androgens.

These findings suggest that there are marked changes in the hypothalamic-pituitary unit around the beginning of the peripubertal stage. These changes could play a determinant role in the onset of puberty.