bluuebunny/crossref_metadata_2025 huggingface dataset:
Bromocriptine treatment of prolactin secreting macroadenomas: a radiological, ophthalmological and endocrinological study
Authors: van 't Verlaat Johanna W. , Croughs Ronald J. M. , Hendriks Martin J. , Bosma Nicolaas J. , Nortier Johan W. R. , Thijssen Joseph H. H.
Published: December 2008

Abstract. Twelve patients, six women and six men, with macroprolactinomas characterized by extrasellar extension and basal plasma prolactin levels >6 U/l were treated with 10–20 mg bromocriptine daily in four divided doses for a mean period of 2.4 years (range 0.5–3.5 years). The following observations were made:

Plasma prolactin levels fell dramatically in all patients and values in the low normal range were obtained in 10 patients.

Tumour size was reduced by more than 75% in 11 patients and by 50–75% in one patient. Tumour-reduction was associated with the development of a partial empty sella in eight cases. In four cases the pituitary became visible.

Diminished visual acuity (three patients), bitemporal hemianopia (three patients), unilateral or bilateral central scotomas (three patients) and oculomotor palsy (two patients) restored to normal.

Hypogonadism (all patients), hypothyroidism (six patients) and hypocorticism (three patients) improved or normalized in most cases. It is concluded that in the medical treatment of macroprolactinomas 10–20 mg bromocriptine in four divided doses effectively reduces both plasma prolactin level and tumour size.
Interactions between TSH binding inhibiting and adenylate cyclase stimulating antibodies in Graves' disease
Authors: Morita Shigeki , Izumi Motomori , Nagataki Shigenobu
Published: December 2008

Abstract. It is well known that there exists a dissociation between TSH binding inhibiting antibody (TBIAb) and thyroid stimulating antibody (TSAb) in some patients with Graves' disease. The present studies were undertaken to investigate the interaction between TBIAb and TSAb quantitatively using porcine thyroid cells in order to determine whether the binding sites of TBIAb and TSAb are identical or independent from each other. TBIAb was determined using solubilized porcine thyroid membrane and TSAb using cultured porcine thyroid cells, and both were expressed as equivalent amounts of bovine TSH. In order to avoid interassay variations, all determinations were performed with a single batch of porcine thyroids. Serum samples were obtained from ten untreated patients with Graves' disease; two were negative for TBIAb and TSAb, two were TBIAb negative and TSAb positive, two were weak positive for both, two were strong positive for both, and two were TBIAb strong and TSAb weak positive. IgG from each patient were mixed with equal amounts of IgG of the other nine patients. In order to observe interactions, measured values for TBIAb and TSAb of mixed samples were compared to estimated values (addition of values of original samples). The correlation coefficient between measured values and estimated values for TBIAb was +0.964, and that for TSAb was +0.989. These results that TBIAb does not interfere with the activity of TSAb and vice versa suggest that at least in some patients with Graves' disease, TBIAb and TSAb are different antibodies which have different binding sites.
Affinity to lectin, biological and immunological characteristics of human chorionic gonadotropins from pregnant women and trophoblastic tumour patients
Authors: Koyama Koji , Toda Kazushi , Kuriyama Daisaku , Isojima Shinzo
Published: December 2008

Abstract. To compare the affinity to lectin of human chorionic gonadotropins (hCG) from pregnant women and trophoblastic tumour patients, a small amount of urine was fractionated by a lentil lectin (LcH) affinity chromatography. The LcH-bound fractions were eluted with 2% mannoside solution, and each fraction was assayed for hCG activities by radioimmunoassay. In pregnant women, more than 90% of hCG immunoactivity in urine was bound to the LcH column and eluted from it, whereas 8 to 26% and 37 to 51% of the activity were not adsorbed to the affinity column and were recovered in the LcH-unbound fraction in the patients with hydatidiform mole and choriocarcinoma, respectively. These results suggest that LcH affinity chromatography of urinary hCG contributes to differential diagnosis between pregnancy and trophoblastic tumours. To characterize the properties of hCG from the urine of choriocarcinoma patients, with or without the LcH affinity, hCG activities in both LcH-unbound and LcH-bound fractions were measured by in vivo and in vitro bioassays and each of the activities was compared with the activities measured by radioimmunoassay. The results showed that the LcH-unbound fraction contained hCG molecules defecting to induce the biological activity of hCG in vivo.
Preparation and properties of human chorionic gonadotropin antagonist for biological studies: antifertility effects in the female rat
Authors: Sairam M. R. , Kato K. , Mukhopadhyay A. K. , Bohnet H. G.
Published: December 2008

Abstract. We compared the effects of treatment of clinical grade hCG powders with anhydrous HF (hydrogen fluoride) or TFMS (trifluoromethane sulfonic acid). HF treatment yielded stable product (DG-hCG), which had desirable antagonistic activity in mouse Leydig cells. Binding of HF-hCG to ovarian granulosa cell FSH receptors was < 5% as compared to purified ovine FSH. As LH/hCG receptor specificity was not significantly compromised crude hCG could be directly used in obtaining large amounts of the antagonist. The effects of antagonist (DG-hCG) and agonists crude hCG and purified hCG were evaluated in pregnant rats. When administered between days 1 to 5 of pregnancy, crude DG-hCG inhibited serum progesterone and oestradiol levels and implantation. The effect was dose-dependent. However, both crude hCG and purified hCG elevated progesterone level and partially inhibited implantation (up to about 40%). In the post-implantation period (days 8–11) crude DG-hCG treatment induced abortion due to a decrease in circulating progesterone and oestradiol levels. The agonists, crude hCG and purified hCG, on the other hand, elevated both steroid levels in serum and induced partial termination of pregnancy (up to 50%). During the second half of pregnancy, when luteotropic support of LH becomes unnecessary in the rat, crude DG-hCG (antagonist) had no effect on parturition. However, crude or purified hCG caused delay in parturition by sustaining high level of progesterone in circulation. Our data demonstrate that the antifertility effects of crude DG-hCG are more potent and consistent than the administration of either crude or purified hCG in the pregnant rat.
Dose and time effects of treatment with low doses of a LRH agonist on testicular axis and accessory sex organs in rats
Authors: Lemarchand-Béraud Th. , Jaussan V. , Zürich M. G.
Published: December 2008

Abstract. LRH and its agonists have been shown to exert both stimulatory and inhibitory effects on testicular function. In the present study, the dose and length of treatment were tested to determine the appearance of the stimulatory and inhibitory effects of LRH agonist on testicular axis including the three levels. Two doses of an agonist of LRH, 40 and 100 ng/100 g body weight (buserelin, 'agonist'), were administered daily for 1 to 15 days to adult male rats. Control rats received the vehicle only. On day 1, 2, 4, 8 and 15 of treatment, the pituitary, testicular and peripheral levels (weight of accessory sex organs and androgen receptors in ventral prostate) were tested 6 h after the last injection. For the 15 days of treatment with both doses, a stimulatory effect of the 'agonist' was observed on LH and FSH release. A short exposure (1–2 days) to the low dose of the 'agonist' had a stimulatory effect on the density of LH/hCG testicular receptors (326 ± 49 vs control 185 ± 2 1 fmol/mg protein, mean ± sem), on the weights of seminal vesicles and ventral prostate and exposure to both doses led to high plasma testosterone levels (13.8 ± 0.5 and 13.7 ± 0.7 ng/ml, respectively, vs control 2.6 ± 0.3 ng/ml), and to an increased density of nuclear androgen receptors in the ventral prostate (142 ± 9 and 144 ± 15 fmol/mg protein respectively vs control 97 ± 12 fmol/mg protein). A prolonged exposure (4–15 days) to both doses of the 'agonist' had a time-dependent inhibitory effect on the density of LH/hCG testicular receptors, the weight of testes, seminal vesicles and ventral prostate. It had no effects on plasma testosterone levels and on the density of nuclear ardrogen receptors in the ventral prostate. These data show that exposure to low doses of the 'agonist' for a short time leads to a stimulatory effect on the pituitary testicular axis in the adult rat, whereas a more prolonged treatment results into a partial inhibition of this axis affecting first the testicular level then the peripheral level but without decreasing the density of androgen receptors in the ventral prostate.
Potentiation of cholinergic tone by pyridostigmine bromide re-instates and potentiates the growth hormone responsiveness to intermittent administration of growth hormone-releasing factor in man
Authors: Massara Ferdinando , Ghigo Ezio , Molinatti Pia , Mazza Enrico , Locatelli Vittorio , Müller Eugenio E. , Camanni Franco
Published: December 2008

Abstract. It is known that in normal subjects repeated administrations of the growth hormone-releasing factor (GRF) induces a state of partial refractoriness of the somatotropes to GRF. Studies were conducted to verify whether the cholinergic system plays a role in the mechanism(s) underlying the reduced GH responsiveness to the neuropeptide. In five healthy men, the GH response to three consecutive injections of GRF (50 μg iv), administered at 2 h intervals, was considerably blunted after the second and third GRF bolus. Administration of the inhibitor of cholinesterase, pyridostigmine bromide (120 mg orally) 30 min before the second GRF bolus, not only restored but greatly potentiated the GH responsiveness to the second GRF bolus. The GH response to the third GRF bolus was not apparently influenced by pre-treatment with pyridostigmine. These data reinforce the view that cholinergic neurotransmission plays an important role in the control of GH secretion in human.
Reduction of pituitary size by the somatostatin analogue SMS 201-995 in a patient with an islet cell tumour secreting growth hormone releasing factor
Authors: Wilson Darrell M. , Hoffman Andrew R.
Published: December 2008

Abstract. Acromegaly is rarely caused by the ectopic secretion of growth hormone releasing factor (GRF) from peripheral neuroendocrine tumours. We evaluated the ability of a recently developed somatostatin analogue (SMS 201-995, Sandoz) to reduce hormone levels and pituitary size in a young woman with acromegaly and Zollinger-Ellison syndrome secondary to a metastatic pancreatic islet cell tumour secreting GRF and gastrin. Gastrin, GRF, and growth hormone (GH) levels declined dramatically following the initiation of therapy with the analogue by continuous iv infusion. Although intermittent sc therapy was not effective in suppressing hormone levels, continuous sc infusion of SMS 201-995 has provided good control of both GRF and GH levels for nine months. Moreover, treatment with SMS 201-995 was associated with a substantial reduction in pituitary enlargement and an improvement in her gastric symptoms. Continuous sc infusion of SMS 201-995 may be useful in treating enlarged pituitaries resistant to other modes of therapy.
Gonadotropin-secreting pituitary adenoma with concomitant hypersecretion of testosterone and elevated sperm count. Treatment with LRH agonist
Authors: Zárate Arturo , Fonseca Ma. Eugenia , Mason Macrina , Tapia Rosario , Miranda Rogelio , Kovacs Kalman , Schally Andrew V.
Published: December 2008

Abstract. Hypersecretion of both FSH and LH was demonstrated in a man with pituitary macroadenoma, who also presented elevated levels of blood testosterone and an increased sperm count. The patient underwent transsphenoidal surgery followed immediately by cranial irradiation. Immunocytochemical analysis of the tumour revealed the presence of FSH, LH, TSH and the α-subunit. Gel chromatography of the serum on Sephadex G-100 revealed immunoactive FSH, LH and the α-subunit which coeluted with the labelled standards of corresponding hormones. Blood levels of both gonadotropins and testosterone remained persistently elevated up to one year following surgical decompression of the tumour and radiotherapy. It was decided to treat this patient with sc administration of 100 μg D-Trp6-LRH biweekly. After 20 weeks, LRH-analogue treatment resulted in the reduction of serum FSH and LH levels and a diminishing in tumour size as assessed by computed tomography scan of the pituitary. This report shows that in a patient with clinically and biochemically documented gonadotropin-secreting adenoma, inducing a state of persistent gonadal hyperfunction, pituitary surgery and cranial irradiation failed to normalize the biochemical abnormality; however, therapy with D-Trp6-LRH agonist induced clinical, biochemical and radiologic improvement.
Autoreactive lymphocytes in thyroid disorders. Quantitation of anti-thyroglobulin antibody formation by a specific haemolytic plaque forming cell (PFC) assay
Authors: Petersen Jøgen , Feldt-Rasmussen Ulla , Larsen Flemming , Siersbæk-Nielsen Kai
Published: December 2008

Abstract. Blood mononuclear cells (MNC) from 21 patients with autoimmune thyroiditis were assayed for secretion of immunoglobulins in vitro by a reverse haemolytic plaque forming cell (PFC) assay. An anti-gen-specific assay was employed to quantify anti-thyroglobulin antibody (TgAb) secreting cells. The sensitivities of the two PFC assays were similar. The antigen specificity of the Tg-PFC assay was demonstrated by the ability of free Tg to inhibit PFC formation.

The number of spontaneous TgAb-secreting cells was low (median 3 IgG-Tg-PFC/106, range 0–35/106); TgAb activity was found in 3% (range 0–11%) of total IgG-PFC. The number of spontaneous IgG-TgAb-secreting cells correlated positively to TgAb titres in serum. MNC from most patients secreted IgG-TgAb upon polyclonal stimulation in vitro for six days with pokeweed mitogen (52 IgG-Tg-PFC/106, range 0–478/106); TgAb activity was found among 2% (range 0–8%) of total IgG-PFC. Again, pokeweed mitogen-induced TgAb secretion correlated positively to TgAb titres in serum. Finally, MNC from most patients secreted TgAb after culture with Tg. The Tg-induced response was about 1/3 of the pokeweed mitogen-induced TgAb response. Tg did not increase the production of total IgG indicating that Tg is not a polyclonal stimulus. Few TgAb-secreting MNC were discovered in euthyroid sex and age-matched control patients.
Insulin binding and action in adipocytes in vitro in relation to insulin action in vivo in young and middle-aged subjects
Authors: Yki-Jarvinen Hannele , Kiviluoto Tuula , Nikkila Esko A.
Published: December 2008

Abstract. The effect of age on glucose metabolism in vivo was compared to that found in adipocytes in vitro in young (n = 8, age 23 to 31 years) and middle-aged (n = 7, age 37 to 55 years) non-diabetic subjects. During the OGTT, the incremental glucose or insulin areas did not differ significantly between the groups. Fasting and 2 h plasma glucose (P < 0.01) and the 2 h plasma insulin (P < 0.05) levels were, however, slightly higher in the middle-aged than in the young group. During iv induced hyperinsulinaemia (~ 85 mU/l), rates of glucose uptake were comparable between the middle-aged (6.32 ± 0.94 mg/kg/min) and the young subjects (7.56 ± 0.78 mg/kg/min, P > 0.5). In fat cells, both basal and insulin stimulated rates of glucose transport were 35% lower (P < 0.05) in the middle-aged than in the young subjects. Basal and insulin stimulated rates of glucose oxidation and lipogenesis were both markedly lower (P <0.01) in the middle-aged than in the young group. The rates of glucose transport, oxidation and lipogenesis were inversely related to age, whereas none of these parameters was related to fat cell size. In conclusion, adipocyte glucose metabolism in middle-aged healthy subjects was markedly impaired. In contrast, rates of glucose uptake during iv hyperinsulinaemia and glucose responses during hyperinsulinaemia in the OGTT were comparable in young and middle-aged subjects. These results indicate first, that changes in adipose tissue glucose metabolism by aging do not parallel changes in whole body glucose metabolism and thus are specific for adipose tissue. Secondly, insulin-mediated glucose uptake is not reduced in middle-aged subjects. Thus, the small elevation in fasting and 2-h glucose levels may reflect a reduction in glucose uptake by non-insulin dependent pathways by aging.
The effects of conjugated equine oestrogens with and without a cyclical progestogen on lipoproteins, and HDL subfractions in postmenopausal women
Authors: Farish Elizabeth , Fletcher Colin D. , Hart David M. , Teo H. T. H. T. Christopher , Alazzawi Farouk , Howie Catherine
Published: December 2008

Abstract. Serum lipoprotein levels were followed for 24 weeks in 21 oophorectomised women treated with conjugated equine oestrogens (0.625 mg/day) and 21 women who had had a natural menopause and were treated with a combined preparation consisting of conjugated equine oestrogens (0.625 mg/day) with the addition of dl-norgestrel (0.15 mg/day) for the last 12 days of each treatment cycle. Conjugated equine oestrogens caused a significant (P < 0.05) increase in triglyceride, HDL cholesterol, especially HDL2 cholesterol, and a significant decrease (P < 0.05) in LDL cholesterol. Those subjects treated with conjugated equine oestrogens plus cyclical norgestrel showed a significant (P < 0.05) decrease in LDL cholesterol levels only.
New injectable testosterone ester maintains serum testosterone of castrated monkeys in the normal range for four months
Authors: Weinbauer G. F. , Marshall G. R. , Nieschlag E.
Published: December 2008

Abstract. Two groups of four long-term orchidectomized cynomolgus monkeys, Macaca fascicularis, weighing 2.8–4.6 kg received either a single intramuscular injection of 40 mg of a new testosterone ester, testosterone-trans-4-n-butylcyclohexyl-carboxylate (20 Aet-1) in an aqueous suspension or 32.8 mg testosterone oenanthate dissolved in sesame oil. Both preparations contained equal amounts of testosterone, namely 23.6 mg. Testosterone oenenthate injections resulted in supraphysiological serum testosterone levels for eight days followed by a rapid decline so that the lower physiological limit was reached after three weeks. In contrast, 20 Aet-1 produced a moderate increase of serum testosterone levels into the physiological range. Serum testosterone remained in this range for a period of 18 weeks. Thus it appears that the 20 Aet-1 may provide a long desired, new modality of testosterone substitution for hypogonadal men as well as for methods of male fertility control.
Hypercholesterolaemia, hypotriacylglycerolaemia and increased lipoprotein lipase activity following orchidectomy in rats
Authors: Haug Anna , Høstmark Arne T. , Spydevold Øystein , Eilertsen Einar
Published: December 2008

Abstract. Plasma lipoproteins, faecal cholesterol excretion, and activities of lecithin: cholesterol acyltransferase (LCAT) hepatic lipase (HL), and lipoprotein lipase (LPL) were determined in castrated rats, in rats treated with testosterone propionate after castration, and in sham-operated controls. Compared to control rats, whole-plasma total cholesterol (TC) rose, and triacylglycerols (TG) fell in castrated rats, but were normalized by androgen substitution. VLDL components tended to be reduced, whereas HDL2 components rose following castration. In general, testosterone substitution normalized the alterations induced by castration. Adipose tissue LPL was higher in castrated rats than in control rats, whereas activities of HL and LCAT were not significantly affected by the treatments. Hepatic cholesterol concentration, and faecal excretion of cholesterol and bile acids were not significantly altered by the treatments. Considering all 3 groups together, there was a significant positive correlation between the concentration of plasma cholesterol and cholesterol in liver, between plasma HDL2-cholesteryl esters and hepatic cholesterol, and also between HL and faecal cholesterol excretion. The results suggest that short term castration of rats causes increased levels of lipoprotein lipase and thereby brings about a lowering of VLDL and an increased concentration of LDL and HDL2. These effects are reflected in hypotriacylglycerolaemia and hypercholesterolaemia.
Sexual dimorphism and testosterone effects on liver epidermal growth factor receptors in mice
Authors: Alm Jan , Lakshmanan Jayaraman , Fisher Delbert A.
Published: December 2008

Abstract. A sexual dimorphism (M > F) for liver EGF receptor binding capacity has been observed in developing mice. To assess the aetiology of this sexual dimorphism we studied the effect of exogenous testosterone administration on liver EGF receptors in adult mice. In control animals the maximal binding capacity of liver EGF receptors in females was 57% of that in males. The affinity konstant (Ka) was 1.59 × 109 l/mol in females compared with 3.11 × 109 in males. Treatment with testosterone every second day for 14 days resulted in an increase in the binding capacity with 17% in males and 80% in females making the maximal binding capacity in females equal to that in untreated males. Receptor Ka was unchanged by treatment in males, but Ka in treated females was increased to the level of males (2.96 × 109 1/mol). These results indicate that the sexual dimorphism of hepatic EGF receptors involves receptor affinity and capacity; both are increased by testosterone in females.
Sellar lesions associated with isolated hyperprolactinaemia Morphological, immunocytochemical, hormonal and clinical results
Authors: Riedel Matthias , Noldus Joachim , Saeger Wolfgang , Lüdecke Dieter K.
Published: December 2008

Abstract. In 204 patients with sellar lesions and isolated hyperprolactinaemia we analysed and compared many different morphological, immunocytochemical, hormonal, and clinical data for a differentiation of primary (Prl produced by a tumour) and secondary (Prl elevation by PIF inhibition) hyperprolactinaemia. We found Prl-positive pituitary adenomas with primary hyperprolactinaemia in 62.7% and a secondary Prl elevation with different alterations in 37.3% (Prl-negative adenomas 28.9%, craniopharyngeomas 5%, and non-tumourous conditions 3.4%). In secondary hyperprolactinaemia the Prl values did not exceed 130 μg/l, higher levels indicated Prl-producing adenomas with a high probability. In patients with Prl elevation below 130 μg/l the clinical and sometimes the morphological analysis were not sufficient for a differentiation. Here immunocytochemical studies are necessary for a clear classification of hyperprolactinaemia.
LT4-monopreparation versus LT4- LT3-compound preparation in the treatment of diffuse endemic goitre
Authors: Bongers H. , Hotze L. A. , Schmitz R. , Joseph K.
Published: December 2008

Abstract. Fifty-four patients with diffuse non-toxic goitre were observed before and under therapy either with 125 μg LT4 (group A) or 75 μg LT4 + 15 μg LT3 (group B) in a prospective double blind study, using 1-, 3- and 6-months controls. Changes in goitre size have been estimated by ultrasonic scanning. Both treatment forms provided a significant reduction of goitre size, even after 1 month of therapy: a 20%-decrease in group A and 16% in group B. The 6-month reduction was about 30% in group A and 27% in group B. Between the 2 groups there were no differences in the reduction of volume. The suppression of the TSH-response to TRH was identical in both groups, too. In group A there was a predominant increase of the TT4-and FT4-serum levels, both reaching the hyperthyroid range. In group B there was a predominant increase of the TT3- and FT3-serum levels and a slight increase of the FT4-levels. The TT3- and FT3-serum levels also exceeded the upper normal range. As the blood samples were drawn about 2 h after medication, acute hormone resorption influenced these data. In the 3-month controls only there was a significant correlation between the reduction of the thyroid volume and the suppression of TSH-release. In the 6-month controls we found a weak correlation of the reduction of volume and the decrease of the pertechnetate uptake value. No correlation was found between the relative changes of FT3- and FT4-serum levels and the reduction of goitre size. There were no indications of possible side effects in group A or B during treatment. So this study showed the compared treatment forms to be equivalent in the therapy of diffuse non-toxic goitre, both yielding excellent results.
Physiological role of thiol proteases in thyroid hormone secretion
Authors: Yoshinari Mototaka , Taurog Alvin
Published: December 2008

Abstract. To determine the physiological role of the thiol proteases in T4 and T3 release from thyroglobulin, experiments were performed with 131I-prelabelled rat thyroid lobes incubated in vitro in the presence and absence of leupeptin, an inhibitor of thiol proteases. Basal secretion of [131I]T4 and [131I]T3 from rat thyroid lobes prelabelled in vivo was quite low, but in the presence of 10 mU/ml bovine TSH a marked stimulatory effect was observed. The stimulatory effect of TSH was completely abolished by leupeptin. This was associated with marked inhibition of lysosomal proteolytic activity, suggesting that the inhibitory effect of leupeptin on T4 and T3 secretion could be attributed to its inhibitory action on proteolysis of thyroglobulin. Further evidence for an inhibitory effect of leupeptin on intralysosomal hydrolysis of thyroglobulin was obtained when thyroid lobes were incubated with 131I- in the presence and absence of leupeptin and TSH. The crude lysosomal preparation was fractionated on a Percoll density gradient, which separates 131I-containing particles into a dense peak containing purified lysosomes and a buoyant peak containing pinocytotic vesicles. A marked increase in the 131I-content of the dense peak was observed in the presence of TSH + leupeptin. Analysis of the 131I in the dense fraction by sucrose density gradient centrifugation and by SDS-polyacrylamide gel electrophoresis demonstrated that leupeptin inhibited degradation of 19S thyroglobulin, especially the formation of [131I]peptides of MW < 14K.
Similar isoelectric profiles of FSH from gonadotroph cell adenomas and non-adenomatous pituitaries
Authors: Chappel Scott C. , Bashey Hildegarde M. , Snyder Peter J.
Published: December 2008

Abstract. Heterogeneity of intact FSH in human pituitary tissue was evaluated by the column isoelectric focusing technique, chromatofocusing. FSH was examined from three autopsy pituitaries, one piece of apparently normal pituitary obtained at surgery, three purified FSH preparations, and four gonadotroph cell adenomas. FSH from all of these sources was found to exist in multiple isoelectric forms. FSH from the gonadotroph cell adenomas exhibited chromatofocusing profiles that were similar, both in the range of pI's and the relative proportions of the FSH isohormones, to those of the non-adenomatous pituitaries. We conclude that gonadotroph cell adenomas produce a population of FSH that is qualitatively normal although quantitatively excessive.
Serotonin stimulates GH secretion through a direct pituitary action: studies in hypophysectomized autografted animals and in perifused pituitaries
Authors: López F. , Gónzalez D. , Aguilar E.
Published: December 2008

Abstract. To analyze a possible direct action of serotonin (5-hydroxytryptamine) at pituitary level in GH secretion, two experimental models were used: hypophysectomized autografted rats and perifused pituitaries. Adult male rats were hypophysectomized and their own pituitaries placed under the right kidney capsule. Ten days later an intra-atrial cannula was inserted. The next day, blood samples were obtained before and every 10 min during a 2 h period after the injection of saline or 5-hydroxytryptamin (1 or 2 mg/kg iv). Plasma volume was replaced with saline. Both doses of 5-hydroxytryptamine elicit a strong release of GH, the effect being dose-dependent. In pituitaries perifused with 5-hydroxytryptamine (100 μm during 115 min or 1, 10 and 100 μm during 15 min), a significant release of GH was also observed. These results suggested that 5-hydroxytryptamine may stimulate GH secretion through a direct pituitary action.
A comparison of porcine and human thyroid tissue in the assay of thyroid stimulating immunoglobulins
Authors: de Rave S. , Goldschmidt H. M.J. , Somers-Pijnenburg Y. T.J. , Bravenboer B. , Lockefeer J. H. M.
Published: December 2008

Abstract. The central role of Thyroid Stimulating Immunoglobulins (TSI) in the pathogenesis of the hyperthyroidism of Graves' disease has become generally accepted and a wide variety of assays for the detection of these antibodies has been developed. The dependence on the availability of human thyroid tissue makes most of these assays unsuitable for routine clinical use, a problem circumvented by the use of nonhuman thyroid tissue in some TSI assays. We therefore compared porcine and human thyroid tissue in a TSI assay based on in vitro cAMP generation. No major differences in within and between run variation were found and, with some notable exceptions, a reasonable correlation could be demonstrated between the results in both assays (R = 0.89, P < 0.001). However, the sensitivity of the porcine TSI assay is only 60% of the estimated sensitivity of the human TSI assay. In spite of the practical advantages this porcine TSI assay, and possibly also other TSI assays using non-human thyroid tissue, cannot totally replace human TSI assays. The value of these assays in predicting the outcome of medical treatment of Graves' disease remains to be established.
Steroidogenic activity of highly potent melanotropic peptides in the adrenal cortex of the rat
Authors: Baumann J. B. , Eberle A. N. , Christen E. , Ruch W. , Girard J.
Published: December 2008

Abstract. Highly purified ACTH and MSH peptides were studied in isolated rat glomerulosa and inner zone cells and their activity compared with that in an Anolis melanophore assay. While both ACTH1-39 and ACTH1-24 were almost equally potent steroidogenic peptides in the two cell types (ED50 between 1 and 4 × 10−12 m), α-MSH displayed only weak steroidogenic activity. Although it was a full agonist, it was about 104-fold less potent in both capsular and inner zone cells. β-MSH (porcine) was even 10-fold less active in capsular cells than α-MSH, and in inner zone cells it was a partial agonist. Highly potent melanotropic peptides, such as (Nle4, D-Phe7)-α-MSH or cyclic (Cys4, Cys10)-α-MSH were either inactive or exhibited only a very slight partial steroidogenic activity in both cell types. Comparison of the activity profile of additional compounds, such as des-acetyl α-MSH, (Tyr(I)2)-α-MSH, (Trp(For)9)-α-MSH or (Nva12-α-MSH in the adrenocortical and pigment cell assays led to the conclusion that α-MSH does not exert its steroidogenic effect through a typical melanocyte-type of MSH receptor, but rather through a low affinity-type of ACTH receptor.
Distribution of ornithine decarboxylase in ovaries of rat and hamster during pro-oestrus
Authors: Persson Lo , Isaksson Karin , Rosengren Elsa , Sundler Frank
Published: December 2008

Abstract. The biosynthesis of polyamines is dramatically increased in the ovaries of rat and hamster during the evening of pro-oestrus. In an attempt to shed some light on the physiological function of this biosynthesis ornithine decarboxylase (ODC), which catalyzes the rate-limiting step in the biosynthesis of the polyamines, was immunohistochemically localized in the ovaries from rat and hamster during pro-oestrus. At dioestrus, only a few immunoreactive cells were found in the ovaries. During the evening of pro-oestrus, on the other hand, numerous immunoreactive cells were observed in the ovaries. These cells were confined to the internal thecal layer of Graafian as well as smaller follicles and to the interstitial tissue of the ovary. The granulosa cells appeared to be devoid of immunoreactive ODC. The hamster ovary, which during this time exhibited considerably higher levels of ODC activity than the ovaries from the rat, did accordingly contain more immunoreactive cells than the rat ovary.
Decreased serum thyroglobulin levels in the late stage of pregnancy
Authors: Hara Yoshihito , Tanikawa Toshinori , Sakatsume Yoshiki , Sato Kentaro , Ikeda Hitoshi , Ishii Jun , Akamine Kazuki , Murayama Yukinobu
Published: December 2008

Abstract. Serum thyroglobulin levels were serially measured in 25 normal pregnant women to evaluate thyroidal activity during normal pregnancy. Measurements included serum T3, T4, free T4, TBG, and TSH. Tg and FT4 levels were found to be decreased in the third trimester when compared with those of the first trimester and with those of normal non-pregnant individuals (P < 0.01). TSH levels were higher than normal in pregnant women at all stages of pregnancy, with a significant rise at the third trimester. These findings suggest the presence of a subclinical hypothyroid state in the late stage of normal pregnancy.
Somatostatin plasma levels and biological effects following subcutaneous administration of somatostatin in man
Authors: Uccioli L. , Ghirlanda G. , Cotroneo P. , Manto A. , Solini A. , Greco A. V.
Published: December 2008

Abstract. The rate at which somatostatin appears in the circulation after subcutaneous bolus injection and continuous administration by pump was determined in normal subjects by serial radioimmunoassays of immunoreactive somatostatin. Following a single subcutaneous injection of 250 μg, the somatostatin peak in plasma appeared after 5 min and had only a transient effect on insulin levels. During continuous administration, somatostatin reached levels able to reduce significantly insulin and glucagon. Somatostatin plasma levels exerting biological effects were observed during the subcutaneous administration of the peptide.
Testosterone stimulates pituitary and serum FSH in GnRH antagonist-suppressed rats
Authors: Rea M. A. , Weinbauer G. F. , Marshall G. R. , Nieschlag E.
Published: December 2008

Abstract. Thirty days of continuous treatment of adult male rats with 35 μg/day of the potent GnRH antagonist, (N-Ac-D-Nal (2)1, D-pCl-Phe2, D-Trp3, D-hArg (Et2)6, D-Ala10)-GnRH (RS-68439) reduced serum FSH to values below the limit of detection of the assay. Testosterone supplementation in the form of subcutaneous testosterone-filled silastic capsule implants present during an additional 30 days of GnRH antagonist administration restored serum FSH to values comparable to those observed after vehicle treatment. Pituitary FSH content, which was substantially reduced after GnRH antagonist treatment, was completely restored after concurrent testosterone supplementation. These results show that, under conditions of GnRH receptor blockade, testosterone is capable of stimulating pituitary and serum FSH in adult male rats.
Evaluation of an enzyme-linked immunosorbent assay for the measurement of autoantibodies against eye muscle membrane antigens in Graves' ophthalmopathy
Authors: Miller A. , Sikorska H. , Salvi M. , Wall J. R.
Published: December 2008

Abstract. We have tested for antibodies against human and pig eye muscle membrane antigens in the serum of patients with Graves' ophthalmopathy using an enzyme-linked immunosorbent assay (ELISA). Several different membrane preparations were used as source of putative antigen including a 100 000 × g pellet, a pellet depleted of the 100 000 × g (microsome) fraction, and solubilized membranes. With eye muscle membrane pellets there were no significant differences for either serum or immunoglobulins between patients with ophthalmopathy, those with autoimmune thyroid disorders without eye disease, and normal subjects for either human or pig membranes, although tests were positive determined from the upper limit of normal in a few patients with or without eye disease. This was the case regardless of the enzyme-antibody conjugate used, the membrane protein concentration or serum or immunoglobulin dilution. Pre-absorption of tissue fractions, serum, or immunoglobulins, with red blood cells or liver powder, eye muscle membranes or skeletal muscle membranes did not significantly reduce background binding which was often very high, or enhance the difference between patients with ophthalmopathy and normal subjects. It was found that non-specific binding to the plastic surface of the microplates and/or tissue proteins, the presence, in human tissues, of blood-derived immunoglobulins which gave strong reactions in the ELISA, and variable fixation of membrane pellets to the plates were factors which made ELISA unsatisfactory when crude membrane pellets were used as antigen. When eye muscle membranes solubilized with standard agents including SDS, Triton X-100 and deoxycholine were tested, again no differences were demonstrated between patients with Graves' ophthalmopathy and normal subjects. However, when membranes were solubilized with the zwitterionic agent 'CHAPSO' approximately 20% of patients with Graves' ophthalmopathy and smaller proportions of patients with thyroid disease without apparent eye involvement had positive tests with both human and pig eye muscle. While availability of human monoclonal antibodies should soon allow the isolation and purification of soluble eye muscle membrane autoantigens for use in sensitive and specific antibody tests, the ELISA, as presently used with crude tissue fractions, appears too variable and prone to non-specific immunoglobulin-binding for routine clinical use.
Immunoextracted calcitonin in milk and plasma from totally thyroidectomized women. Evidence of monomeric calcitonin in plasma during pregnancy and lactation
Authors: Bucht Elisabet , Telenius-Berg Margareta , Lundell Göran , Sjöberg Hans-Erik
Published: December 2008

Abstract. The level of immunoreactive calcitonin in the first produced breast milk was in totally thyroidectomized (TX) women 713 ± 307 pg-eq/ml (mean ± sd, N = 7) and in control women 772 ± 329 pg-eq/ml (N = 33), i.e. about 45 times higher than in plasma (see below). On gel chromatography of immunoextracted milk from TX women, immunoreactive calcitonin appeared as high molecular weight forms in the same pattern as in milk from healthy women when the same antiserum (1) was used for immunoextraction and radioimmunoassay (RIA). In another series of experiments, a new antiserum (2) raised in rabbits was used for measurement of immunoreactive calcitonin after immunoextraction with 1. Plasma levels of immunoreactive calcitonin in the TX women during pregnancy were 16 ± 6 pg-eq/ml (N = 6) and during lactation 14 ± 7 pg-eq/ml (N = 5). Immunoreactive calcitonin was undetectable (< 8 pg/ml) in plasma from those TX women in whom lactation had stopped (N = 5). Immunoextraction and gel chromatography of plasma collected during pregnancy and lactation from the TX women showed that the immunoreactive calcitonin present eluted in the region of monomeric calcitonin with both antiserum 1 and 2. In conclusion, high concentrations of high molecular weight forms of immunoreactive calcitonin have been demonstrated in milk from TX patients, most probably devoid of any calcitonin-producing thyroid C-cells. This points to a local production site in the mammary gland. Relatively high levels of immunoreactive calcitonin in plasma during pregnancy and lactation in TX women also indicate extrathyroidal production.
Low concentrations of interleukin-1 stimulate and high concentrations inhibit insulin release from isolated rat islets of Langerhans
Authors: Spinas Giatgen A. , Mandrup-Poulsen Thomas , Mølvig Jens , Bæk Leif , Bendtzen Klaus , Dinarello Charles A. , Nerup Jørn
Published: December 2008

Abstract. Isolated rat islets were incubated either with crude, affinity-purified or recombinant human interleukin-1 for 1 to 6 days. A significant (20–60%) increase of insulin release was observed at low concentrations of all three interleukin-1-containing preparations. In contrast, higher concentrations dose-dependently inhibited the insulin release. The increased insulin secretion occurred at concentrations below those necessary to augment the mitogen response to phytohaemagglutinin of murine thymocytes in vitro. These doses (0.05-0.5 U/ml) correspond to 0.2-2 ng of recombinant interleukin-1 per ml, equal to approximately 0.01-0.1 pmol/ml. In doses of 0.6-1.8 U/ml affinitypurified interleukin-1 significantly increased the islet insulin content per ng of DNA, indicating a stimulation of insulin-biosynthesis. The data support the concept that low concentrations of interleukin-1 may play a role in priming the physiological secretion of insulin.
Localization of oxytocin and neurophysin in baboon (Papio anubis) corpus luteum by immunocytochemistry
Authors: Khan-Dawood Firyal S.
Published: December 2008

Abstract. Immunoreactive oxytocin is detectable in the corpora lutea of women and cynomolgus monkeys by radioimmunoassay. To localize the presence of oxytocin and neurophysin I in ovarian tissues of subhuman primates, three corpora lutea and ovarian stromal tissues and two Fallopian tubes obtained during the menstrual cycle of the baboon and decidua from two pregnant baboons were examined using highly specific antisera against either oxytocin or neurophysin I and preoxidase-antiperoxidase light microscopy immunohistochemistry. Oxytocin-like as well as neurophysin I-like immunoreactivities were found in some cells of all the corpora lutea only, but could not be demonstrated in ovarian stromal tissues, Fallopian tubes and decidua. Specificity of the immunocytochemical reaction was further confirmed by immunoabsorption of the antiserum with excess oxytocin or neurophysin, after which the immunoreactivities for both oxytocin and neurophysin in the luteal tissue were negative. Similar controls using normal rabbit serum gave no positive staining for either oxytocin or neurophysin. Counterstaining of the positive immunoreactivities for oxytocin and neurophysin I with Mayer's haematoxylin and eosin demonstrated clearly that the oxytocin and neurophysin I appeared as granular material mainly within the cytoplasm of the luteal cells. The localization of immunoreactive oxytocin and neurophysin I in the corpus luteum of the baboon demonstrates directly the presence of these two neurohypophysial peptides within primate luteal cells and suggests their local production.
Growth promoting effect of head activator in cultured chick embryo brain cells
Authors: Kajiwara Sohei , Sato Tamotsu
Published: December 2008

Abstract. To investigate the regulatory role of head activator (HA) and its synthetic analogue, (Arg1,Phe5)-HA(AHA) on brain cell growth, we measured serial uptakes of [3H]thymidine, [3H]uridine and [3H]leucine and changes in cyclic AMP content in cultured chick embryo brain cells. HA stimulated all of these uptakes at a concentration of 10−10m, while 10−9m AHA suppressed them. The stimulatory effect of HA on [3H]thymidine uptake was observed after 4 h of the treatment, reached a maximum of 200% of the initial value at 8 h and declined to the pre-treatment level at 14 h. [3H]uridine uptake began to increase after 6 h of HA treatment, and the effect lasted for 4 h. Increase in [3H]leucine followed after 12 h and sustained for 4 h. Prior to the initiation of HA stimulation, cyclic AMP also began to rise, reaching 170% of the pre-treatment level at 6 h. In contrast, depression of [3H]thymidine uptake by AHA was noted at 6 h and continued for 8 h. Uptake of [3H]uridine and [3H]leucine showed similar tendency. Cyclic AMP in AHA-treated cells at 6 h was significantly lower than that in non-treated cells. These results indicate that HA stimulates DNA, RNA and protein synthesis in an early stage of growing brain cells, in which cAMP may be involved as a regulator of nerve cell growth.
The pituitary TSH response to TRH is inversely related to the plasma TSH concentration and directly related to the pituitary TSH content during hypothyroidism in the rat
Authors: DeVito William J. , Connors John M. , Hedge George A.
Published: December 2008

Abstract. We studied the effects of degree and duration of hypothyroidism on the pituitary TSH concentration and the pituitary TSH secretory response to TRH. Varying degrees of hypothyroidism were achieved in thyroparathyroidectomized rats (THYREX) by continuous sc infusion of T3 (0.2, 0.3, 0.4, or 0.5 μg/100 g · day) or T4 (0.6, 1.2, or 1.8 μg/100 g · day). While T3 was more potent than T4, both resulted in a dose-dependent suppression of the post-thyroidectomy rise in TSH. After 7 or 14 days of severe hypothyroidism (non-replaced THYREX rats) the pituitary TSH secretory response to TRH (250 ng/100 g body weight, iv) was found to be decreased when compared to that of euthyroid rats. Decreasing the degree of hypothyroidism increased the pituitary secretory response to TRH and the pituitary TSH content. The results indicate that in the hypothyroid rat: 1) severe hypothyroidism results in a blunted pituitary TSH response to TRH through 14 days after thyroidectomy, 2) at 7 and 14 days after thyroidectomy the pituitary TSH response to exogenous TRH is inversely related to the basal plasma TSH concentration, 3) the pituitary TSH concentration increases with the duration of hypothyroidism, 4) the pituitary TSH content is increased by low rates of thyroid hormone replacement, and 5) the pituitary TSH response to exogenous TRH is directly related to the pituitary TSH content.
Diabetogenic action of streptozotocin: essential role of membrane permeability
Authors: Beppu Hidehiro , Maruta Kazuhiro , Kürner Thomas , Kolb Hubert
Published: December 2008

Abstract. A single high dose of streptozotocin was found to cause a transient increase in islet capillary permeability 2-4 h after administration. Staining of areas of increased vascular permeability by Evans blue showed that islets, but not exocrine tissue, were affected. The permeability increase seems to involve vasoactive substances released by mast cells. A mast cell inhibitor (disodium cromoglycate) and a serotonin antagonist (methysergide) were found protective. Furthermore, administration of methysergide partially prevented the development of hyperglycaemia in streptozotocin-treated rats. In mice, almost full protection from diabetes development was reached by both methysergide and disodium cromoglycate. Our observations indicate an important role of mast cell controlled membrane permeability in this model of β-cell destruction and diabetes development.
Failure to induce puberty in a man with X-linked congenital adrenal hypoplasia and hypogonadotropic hypogonadism by pulsatile administration of low-dose gonadotropin-releasing hormone
Authors: Kikuchi Kiyoshi , Kaji Masayuki , Momoi Toru , Mikawa Haruki , Shigematsu Yosuke , Sudo Masakatsu
Published: December 2008

Abstract. To elucidate the mechanism of hypogonadotropic hypogonadism in a patient with X-linked congenital adrenal hypoplasia, we studied the effects on serum LH and FSH of repeated iv administration of GnRH (400 μg, over 2 h, once a day, for 14 consecutive days), pulsatile sc administration of GnRH (5 μg every 90 min during days 1 ~ 56, 10 μg every 90 min during days 57 ~ 91) and an iv bolus injection of 10 mg of naloxone. The repeated administration of GnRH restored the hyporesponsiveness of serum FSH and increased serum testosterone level from < 1.0 to 1.7 nmol/l, but the impaired LH response to the standard GnRH test was not improved. The pulsatile administration of GnRH for 91 consecutive days did not induce a clinical or a biochemical change of puberty. Serum testosterone remained undetectable < 1.0 nmol/l, the hyporesponsiveness of serum LH was not improved, but basal FSH level was significantly increased and the impaired FSH response to the standard GnRH test was slightly improved. Naloxone had no effect on serum LH or FSH before or during the pulsatile administration. We conclude that hypogonadotropic hypogonadism in our patient is due to the pituitary dysfunction and that the endogenous opioid peptides may not play a role in the mechanism of inhibited gonadotropin secretions.