bluuebunny/crossref_metadata_2025 huggingface dataset:
Activation of membrane-bound adenylcyclase by thyroid stimulating antibodies
Authors: Karlsson F. Anders , Dahlberg Per Anders , Wålinder Olov
Published: December 2008

Human thyroid plasma membranes isolated from thyroids from patients with Graves' disease or non-toxic nodular goitres produced, under basal conditions, about 100 pmol cAMP per mg membrane protein in 30 min at 37°C. TSH increased the membrane response from a Graves' thyroid by up to 11-fold. cAMP production with immunoglobulins from patients with Graves' disease was four times that from normal immunoglobulins. The onset of action of thyroid stimulating antibodies (TSAb) was rapid and persisted for 30 min of incubation. A change of incubation buffer from 20 mm to 200 mm Tris-HCl reduced the degree and altered the pattern of immunoglobulin stimulation, whereas maximal TSH stimulation was unchanged. The in vitro interaction between the TSH receptor system and TSAb or TSH will differ according to the conditions used.
The synthesis and release of TSH in the thyroidectomized rat: c) the effect of T3 on hypothyroidism of varying duration
Authors: Spira Ofra , Gross Jack , Gordon Amirav
Published: December 2008

The effect of thyroid hormones on TSH synthesis and release from the anterior pituitary of the rat, at the various stages of hypothyroidism was studied by injecting L-Triiodothyronine (T3) iv (1.5 μg/100 g b.w.) to rats 5 days and 3 months post thyroidectomy (Tx-5d and Tx-3m rats). The changes in plasma and pituitary TSH levels, as well as in the metabolic clearance rate (MCR) of the TSH were followed for 3 days after the T3 injection. From these data TSH synthesis and release rates were determined. TSH release was inhibited in both experimental groups between 3 and 24 h after the injection. TSH synthesis was suppressed in the Tx-5d group to 35% of the initial value. However in the Tx-3m group it was stimulated to approximately 270%, 24 h after the T3. The data suggest that thyroid hormones may affect the synthesis of TSH in two opposite pathways, the first through the stimulation of protein synthesis and the second, inhibitory, as part of the feedback mechanism. Under short-term hypothyroidism, when protein synthesis is not yet diminished, the administration of thyroid hormones results in the inhibition of both TSH synthesis and release through the feedback regulation. In prolonged hypothyroidism, however, when protein synthesis is depressed, the effect of thyroid hormones on the stimulation of TSH synthesis predominates.
Thyroid hormone-catecholamine interrelationships during exposure to cold
Authors: Storm H. , van Hardeveld C. , Kassenaar A. A. H.
Published: December 2008

Basal plasma levels for adrenalin (A), noradrenalin (NA), l-triiodothyronine (T3), and l-thyroxine (T4) were determined in rats with a chronically inserted catheter. The experiments described in this report were started 3 days after the surgical procedure when T3 and T4 levels had returned to normal. Basal levels for the catecholamines were reached already 4 h after the operation.

The T3/T4 ratio in plasma was significantly increased after 3, 7, and 14 days in rats kept at 4°C and the same holds for the iodide in the 24-h urine after 7 and 14 days at 4°C. The venous NA plasma concentration was increased 6- to 12-fold during the same period of exposure to cold, whereas the A concentration remained at the basal level.

During infusion of NA at 23°C the T3/T4 ratio in plasma was significantly increased after 7 days compared to pair-fed controls, and the same holds for the iodide excretion in the 24-h urine. This paper presents further evidence for a role of the sympathetic nervous system on T4 metabolism in rats at resting conditions.
The TSH response to TRH is exaggerated in primary testicular failure and normal in the male castrate
Authors: LeRoith D. , Liel Y. , Sack J. , Livshin Y. , Laufer N. , Schenker J. , Spitz I. M.
Published: December 2008

Basal TSH levels and the TSH response to TRH have been evaluated in 26 males aged 20–48 years with primary testicular failure, and 6 males aged 58–69 years who had been orchidectomised for prostatic carcinoma. The patients with testicular failure were sequentially challenged at 30 min intervals with iv LRH (100 μg), TRH (200 μg) and the dopaminergic antagonist, metoclopramide (10 mg). The castrates received a bolus of LRH and TRH given together. The responses in the 2 patient groups were compared to a group of 28 healthy male controls aged 20–40 years, who received the sequential protocol and 8 elderly controls aged 65–79 years, who were given the LRH, TRH bolus.

Mean ± SD basal TSH levels were 3.0 ± 1.2 μU/ml in primary testicular failure and significantly greater than both control and castrate groups. The peak TSH response to TRH was 18.4 ± 7.4 μU/ml in testicular failure and significantly greater than in the young controls, where it was 11.5 ± 5.0 μU/ml. The peak levels in the castrates and in the elderly controls were similar to the young male controls. Total T4 and T3, as well as FTI, were similar in all groups, although the subjects with primary testicular failure had a reduction in their T3 resin uptake. The normal TSH profile in the castrates indicates that a testicular factor produces the exaggerated responses in primary testicular failure.
Direct evidence in men for a role of endogenous oestrogens on gonadotrophin release
Authors: D'Agata R. , Vicari E. , Aliffi A. , Gulizia S. , Palumbo G.
Published: December 2008

In six healthy subjects serum oestradiol was selectively decreased by administering an aromatase activity inhibitor, hydrotestolactone (HT). After HT administration serum oestradiol (Oe2) decreased from 18.7 ± 2.3 (sem) to 6.7 ± 0.6 pg/ml whereas testosterone (T) and dihydrotestosterone (DHT) blood levels were not modified. These oestradiol changes were associated with a significant increase in serum LH and FSH concentrations (P < 0.001). The administration of tamoxifen, an oestrogen antagonist, to 5 subjects caused a sharp increase in LH and FSH levels (P < 0.001).

Oe2 was unchanged after the treatment with tamoxifen, whereas T levels were significantly higher.

The sum of these data suggests that oestradiol under physiological conditions plays a specific role in the feedback mechanism of gonadotrophin release.
Opiate receptors and anterior pituitary hormone secretion in man. Effect of naloxone infusion
Authors: Delitala G. , Devilla L. , Arata L.
Published: December 2008

The role of endogenous opioid receptors on anterior pituitary hormone secretion was evaluated by the administration of the opioid receptor antagonist naloxone. The infusion of naloxone (8 mg iv followed by 4 mg/h for 3 h) did not alter basal growth hormone (GH), prolactin (Prl) and thyrotrophin (TSH) secretion but produced a significant rise in cortisol and gonadotrophins in normal man. The infusion of the opiate antagonist appeared to increase the rate and amplitude of luteinizing hormone (LH) pulsatility.

Naloxone pre-medication (10 mg iv 30 min before testing) did not alter the pituitary response to TRH and LRH stimulation.

These results demonstrate that naloxone can modify basal anterior pituitary hormone secretion and strongly suggest an endogenous opioid modulation of some of these hormones.
Gonad-gonadotrope interactions: plasma gonadotrophin levels and tumour induction in long-term castrated rats
Authors: Linkie Daniel M. , Furth Jacob , Kourelakos Diane
Published: December 2008

The patterns of gonadotrophin secretion in intact controls and in male and female rats castrated for up to 36 months were established utilizing specific radioimmunoassay methods. Plasma LH increased 14– 16-fold and FSH rose 4–8-fold in rats of either sex in the first 30 days following gonadectomy. The subsequent 30 day interval showed an additional 76% increase of LH in both sexes and increases in FSH of 32 and 61% in males and females, respectively. These levels were maintained for an additional 34 months. The number of hypophyseal gonadotrophin containing cells, studied by immunohistochemical localization techniques, increased following gonad removal in a pattern similar to that for the circulating hormones. Development of gonadotrophin secreting tumours did not correlate with plasma gonadotrophin concentrations which suggests that the gonadotropes are uniquely resistant to tumourogenesis unlike mammotropes, thyrotropes, and corticotropes.
A radioimmunoassay of serum 3,5-diiodothyronine
Authors: Kirkegaard Carsten , Faber Jens , Siersbæk-Nielsen Kaj , Friis Thorkild
Published: December 2008

A radioimmunoassay (RIA) for serum 3,5-diiodothyronine (3,5-T2) was developed using small Sephadex G 25 (fine) columns. Prior to the RIA an alcohol extraction of 3,5-T2 from serum and an evaporation of the extract was performed. The recovery of 3,5-T2 added to serum was in mean (± sem) 101 ± 11%. The lower detection limit was 0.012 pmol/column corresponding to 14 pmol/l using 3 ml serum. Due to a 5% cross-reaction of the 3,5-T2 antibody with 3,5,3'-triiodothyronine (T3) individual correction for T3 present in serum was necessary. Serum 3,5-T2 levels in 52 éuthyroid controls were (mean ± SD) 105 ± 51 pmol/l. Serum levels were higher in men (125 ± 56 pmol/l) than in women (84 ± 34 pmol/ l, P < 0.005). In 17 hyperthyroid subjects serum 3,5-T2 levels were elevated (232 ± 187 pmol/l, P < 0.005). In hypothyroid patients and patients with non-toxic goitre serum 3,5-T2 levels did not differ significantly from control values, whereas 8 patients with liver cirrhosis had severely reduced serum 3,5-T2 concentrations (20 ± 23 pmol/l, P < 0.001).
Effect of inhibition of protein synthesis on thyroid cyclic AMP accumulation in vitro
Authors: Nilsson Hans , Ahrén Bo , Gustafson Åsa , Hedner Pavo
Published: December 2008

When thyroid cells in vitro are stimulated by TSH for 2 h cyclic AMP (cAMP) is synthetized at a high rate during the first 25 min of stimulation, thereafter at a lower rate. The mechanism for this reduction of adenyl cyclase activity was studied in vitro using mouse thyroid tissue. As some of the cAMP formed is released from the cells the sum of cAMP in tissue and incubation medium was studied and considered to reflect the accumulated cAMP synthesis as breakdown by phosphodiesterase was minimized by 1 mm theophylline.

The TSH stimulated tissue did not release any adenyl cyclase inhibiting factor into the incubation medium. Cycloheximide, 5 μg/ml, enhanced the cAMP response to a single or repeated stimulation by TSH. Its effect was visible after 25 min of incubation and remained at about the same size for 2 h, but the levelling off of cAMP synthesis was not prevented but took place at a higher level. The effect of puromycin, 500 μg/ml, was similar to that of cycloheximide. Also actinomycin D, 1 μg/ml, enhanced the cAMP response to TSH.

It is concluded that a protein synthesis dependent inhibitor of adenyl cyclase is activated by TSH, but it accounts only for a minor part of the adenyl cyclase inhibition that takes place in the later part of a TSH stimulation of the thyroid. Additional adenyl cyclase inhibiting mechanisms must be considered.
Radioimmunoassay for 4-hydroxyoestrone in human urine
Authors: Emons Günter , Mente Claudia , Knuppen Rudolf , Ball Peter
Published: December 2008

Under the protection of ascorbic acid a 4-hydroxyoestrone-bovine serum albumin conjugate was prepared containing intact 4-hydroxyoestrone as determined by gas chromatography-mass spectrometry. Using this antigen, antibodies with high affinity and specificity for 4-hydroxyoestrone were raised in rabbits. An assay procedure for the determination of 4-hydroxyoestrone in human urine and the assessment of its reliability are described. The following urinary excretion rates were found: male children 0.29 μg/24 h, female children 0.35 μg/24 h, men (20–40 years) 1.6 μg/24 h, men (>50 years) 1.8 μg/24 h, women, follic. 2.0 μg/24 h, pre-ov. 5.3 μg/24 h, luteal 2.4 μg/24 h, women, pregnant, first trim. 30.0 μg/24 h, second trim. 64.0 μg/24 h, third trim. 48.0 μg/24 h, women, post-men. 1.5 μg/24 h. Thus the amounts of 4-hydroxyoestrone excreted in human urine are about 1/3 to 1/10 of those of 2-hydroxyoestrone. During the menstrual cycle the excretion rates of 4-hydroxyoestrone are in the same order of magnitude as those of oestradiol and show a clear-cut pre-ovulatory peak.
Gel filtration and sedimentation behaviour of receptor-gonadotrophin complexes from rat ovary
Authors: Jääskeläinen Kalle , Rajaniemi Hannu , Reichert Leo E.
Published: December 2008

Membrane particles of luteinized rat ovaries and immature and mature granulosa cells of rat ovarian follicles were labelled with [125I]human chorionic gonadotrophin (hCG), membranes of mature granulosa cells were also labelled with [125I]ovine follitropin (oFSH). Hormone-receptor complexes were solubilized with Triton X-100 and their physical properties were characterized by sedimentation and gel filtration. No difference in the macroscopic physical properties of the specific receptor-hCG-complex was observed between different developmental stages of granulosa cells. The Stokes radius of the specific receptor-[125I]hCG-complex was 58 Å and the sedimentation coefficient 6.7 ± 0.3 S.

The physical properties of free LH/hCG-receptor of luteinized ovaries were also characterized. The Stokes radius was found to be 57–59 Å and the sedimentation coefficient 4.8–5.6 S. Both [125I]hCG and [125I]oFSH formed non-specific complexes with ovarian as well as with non-gonadal membrane components. The sedimentation coefficient of the non-specific complex was 1.3 ± 0.5 S and the Stokes radius 49 Å. These results show that the macroscopic physical properties of the receptor-hCG-complex do not change during the maturation and subsequent luteinization of the granulosa cells. The methods used were not enough discriminating to reveal the existing structural differences between receptor-oFSH-complex and receptor-hCG-complex.
The interaction of sialidase-treated hCG with ovarian cellular membranes
Authors: Brand E. C. , Odink J. , Klok G. , van Hall E. V.
Published: December 2008

The potency of human chorionic gonadotrophin (hCG) in competition for binding to a gonadal membrane fraction is remarkably enhanced by sialidase treatment. The present study was undertaken to investigate the specificity and characteristics of the binding of sialidase-treated hCG (asialo-hCG) in a particulate hCG-binding system from luteinized rat ovaries.

The competitive potency of asialo-hCG relative to hCG was 2.5, irrespective of whether [125I]hCG or [125I]asialo-hCG was used for tracer. This was due to a 2.1 times higher equilibrium association constant for asialo-hCG, whereas the estimated number of binding sites did not differ. There was no apparent difference in the stability of hCG and asialo-hCG, or in the stability of the respective hormone-receptor complexes. The effect of variation of the incubation conditions on the binding of both tracers was similar.

In accordance with the difference in the equilibrium association constant, the association velocity of asialo-hCG was more than double that of hCG.

With all of the tracers used the dissociation curves were biphasic, the size of the initial fast-dissociating fraction being inversely related to the pre-incubation time. Under identical conditions, the fast-dissociating fraction was smaller for the [125I]asialo-hCG complex than for the [125I]hCG complex. The dissociation velocities of these fractions appeared to be similar.

The results indicate that asialo-hCG binds to the hCG receptor in a way similar to the binding of the unmodified hormone, but with a higher affinity. The smaller size of the fast-dissociation form of the asialo-hCG-receptor complex may be related to the lower biological potency of the hormone derivative.
Convergence of two types of familial short stature in a pedigree
Authors: Mollica F. , Li Volti S. , Pavone L. , Vigo R. , Raiti S.
Published: December 2008

This study reports an unusual family with coexistence of isolated growth hormone deficiency transmitted as an autosomal dominant trait (Rimoin Type II) and constitutional short stature.
On the mechanism of action of progestins
Authors: Pérez-Palacios Gregorio , Fernández-Aparicio María A. , Medina Martha , Zacarías-Villareal Jesús , Ulloa-Aguirre Alfredo
Published: December 2008

The effect of two synthetic injectable progestins, norethisterone oenanthate3 (NET-e) and medroxyprogesterone acetate (MPA) upon the hypothalamic pituitary unit was evaluated in post-menopausal women (PMW) and in castrated individuals with androgen un-responsiveness in order to gain insight into their mechanism of gonadotrophin inhibition. Continuous administration of natural progesterone (P4) to PMW by medicated vaginal rings was used as the experimental control. Elevated base line levels of serum immunoreactive gonadotrophins and normal pituitary LRH responses were found in PMW and pseudohermaphrodites. Progesterone did not affect circulating gonadotrophin levels or the pituitary LRH response in PMW.

Administration of MPA 150 mg induced a clear decrease in serum gonadotrophins and a significant decrease in LRH pituitary responsiveness in a post-menopausal woman whereas no effect was observed on serum gonadotrophins and pituitary response to LRH in a patient with androgen unresponsiveness. Administration of NET-e 200 mg resulted in a significant decrease in circulating gonadotrophins in PMW and pseudohermaphrodites, while LRH pituitary sensitivity was diminished in all subjects except one post-menopausal woman.

These results demonstrated that two structurally different synthetic progestins (NET-e and MPA) had a potent gonadotrophin inhibitory activity in PMW while natural progesterone did not, thus indicating a different mode of action. Furthermore their differing effect on individuals with complete androgen unresponsiveness suggested that antigonadotrophic activity of NET-e is mediated by its oestrogenic-progestational effect, while MPA acts through its androgenic potency and therefore requires the presence of androgen receptors.
Changes in serum somatomedin A and its binding to kidney membranes in growing rats
Authors: Hizuka Naomi , Takano Kazue , Shizume Kazuo , Hasumi Yoko
Published: December 2008

Changes in serum somatomedin A levels and [125I]somatomedin A binding to membrane fractions from kidney were studied in rats 1–80 days of age. The mean level of serum somatomedin A was 0.80 U/ml at birth and increased with age; at 80 days the mean level was 7.41 ± 0.67 U/ml. There was a close correlation between serum levels of somatomedin A and body weight. Labelled somatomedin A binding to membrane fractions from kidney was highest at birth and decreased with age up to 50 days. In Scatchard analysis of the data the affinity constant did not show a clear change with age, but the binding capacity decreased with age up to 30 days. An inverse correlation was observed between serum somatomedin A levels and labelled somatomedin A binding to membrane fractions from kidney. Compared to changes in circulating somatomedin A, the change in tissue binding was modest. This observation suggests that other circulating growth factors not measured by this radioreceptor assay or altered post-receptor sensitivity to somatomedins may be involved in growth.
Effect of different calcium intakes on bone mineral composition in rats with a calcitonin secreting tumour
Authors: Myhre Lisbeth , Hongslo Cecilie F. , Gautvik Kaare M. , Ekeland Arne
Published: December 2008

The effects of hypercalcitoninaemia and different calcium intakes on bone composition were studied in rats with and without a transplanted calcitonin secreting tumour (MCT). The serum concentrations of immunoreactive calcitonin (iCT) increased progressively after transplantation. After 32 weeks the serum iCT concentrations in MCT rats were about 5-fold higher and serum ionized calcium was significantly reduced compared to control animals. In rats with hypercalcitoninaemia eating a standard calcium (0.9%) diet for 32 weeks, the dry weight and calcium and sodium content of the long bones were reduced compared to control rats without tumours or rats with a prolactin secreting tumour.

The feeding of low (0.09%), medium (0.4%) and high (1.8%) calcium diets to MCT-rats resulted in corresponding levels of total and ionized serum calcium, but there was no difference in iCT concentrations. The MCT-rats taking the low calcium diet had decreased bone mass and calcium content compared to the other dietary groups.

In conclusion, rats on normal calcium intake and carrying a calcitonin secreting tumour, but not a prolactin secreting tumour, had reduced femoral dry weight and bone mineral calcium content. Different calcium intake regimens did not affect hypercalcitoninaemia due to a tumour, but parallel changes in femoral dry weight and calcium content were found.
Presence of TRF immunoreactivity in marginal islet cells in rat pancreas
Authors: Koivusalo F. , Leppäluoto J. , Knip M. , Rajaniemi H.
Published: December 2008

Isolated rat pancreatic islet extracts were submitted to reverse phase high pressure chromatography (HPLC) and assayed for thyrotrophin releasing factor (TRF), glucagon and insulin in radioimmunoassays (RIA). Our anti-TRF serum was prepared by immunizing rabbits with TRF conjugated to bovine thyroglobulin (bTG) by bisdiazobenzidine. Anti-glucagon and anti-insulin sera were from a commercial source (Novo, Denmark). The concentrations of TRF, glucagon and insulin were 0.05 ± 0.02, 0.06 ± 0.02 and 1.0 ± 0.2 pmol/islet, respectively.

Formalin-fixed pancreatic sections were stained for TRF, glucagon and insulin by peroxidase, antiperoxidase (PAP) complex method. When the adjacent sections were stained for glucagon or insulin, it was observed that TRF and glucagon-specific peroxidase reactions were confined to the marginal islet cells, but insulin reactions to the central cells. The TRF-specific peroxidase reaction was clearly reduced when the anti-TRF serum was adsorbed with TRF-TG-Sepharose, whereas it was unchanged when the antiserum was pre-incubated with synthetic TRF.

The present HPLC results suggest that the islets contain TRF. Immunocytochemical studies show that the TRF-immunoreactive material, either synthesized or bound, is localized in the marginal islet cells.
Immunochemical characterization and distribution of calcitonin in the lizard
Authors: Galan F. Galan , Rogers R. M. , Girgis Samia I. , Arnett T. R. , Ravazzola Mariella , Orci L. , Maclntyre I.
Published: December 2008

Immunological and chromatographic methods were used to investigate the distribution of calcitonin (CT) in various tissues of Lacerta muralis, a common wall lizard. Salmon CT-like immunoreactivity was found in high concentration in extracts of ultimobranchial gland (UBG) and in significant amounts in lung and brain extracts, but not in other tissues (oesophagus, stomach, duodenum, liver, skin, muscle and thyroid). Serial dilution of UBG, lung and brain extracts gave parallel displacement curves to that of synthetic salmon CT (sCT), but no reactivity was found in the human CT assay.

On Sephadex G-50, UBG, lung and brain extracts contained an sCT-like immunoreactive peak which co-eluted with synthetic sCT. However, on high performance liquid chromatography (HPLC) the sCT-like peak in UBG, lung and brain extracts eluted 2 ml later than synthetic sCT.

This paper describes the first immunochemical characterization of CT in the UBG of the lizard, demonstrates the distribution of extra-ultimobranchial CT and throws some light on the evolution of the calcitonins.
Inhibition of luteinizing hormone release by dopamine infusion in healthy women and in various pathophysiological conditions
Authors: Ferrari Carlo , Rampini Pietro , Malinverni Aurelio , Scarduelli Claudia , Benco Rosanna , Caldara Roberto , Barbieri Cristiano , Testori Gianpaolo , Crosignani Pier Giorgio
Published: December 2008

To investigate the effect of dopaminergic stimulation on gonadotrophin release, serum LH and FSH concentrations were measured during dopamine infusion (5 μg/kg/min for 120 min) in 8 healthy women in the early follicular phase, in 12 patients with hyperprolactinaemic amenorrhoea, in 5 subjects with premature ovarian failure and in 8 with polycystic ovarian disease and raised serum LH levels. Dopamine infusion produced a significant LH decrease compared with a control study using saline in all groups; there were no significant changes in FSH concentration. Between groups analysis showed a significantly greater LH fall in patients with polycystic ovarian disease than in the other groups.

Dopamine inhibits LH release in healthy women and patients with anovulatory states of varying aetiology, and enhanced sensitivity to this inhibitory mechanism exists in polycystic ovarian disease. This finding suggests reduced dopamine activity at the median eminence level in this condition.
Effect of synthetic thyrotrophin-releasing hormone and its analogues on growth hormone secretion in the domestic fowl (Gallus Domesticus)
Authors: Scanes C. G. , Harvey S. , Morgan B. A. , Hayes M.
Published: December 2008

Variations in plasma growth hormone (GH) concentrations following iv or sc administration of synthetic thyrotrophin-releasing hormone (TRH, Pyr-His-Pro-NH2) have been followed in immature and adult domestic fowl. TRH markedly stimulated GH secretion in newly hatched (1 and 2 day old) chicks and in 6-week-old cockerels but in adult male or female birds of two strains had very little effect, if any. Intravenous injection of 4 TRH analogues (Pyr-His-Mep-NH2, Pyr-Meh-Mep-NH2, Pyr-Meh-Mep-NH and Pyr-Meh-Pro-NH2) were also potent GH secretagogues in 6-week-old birds. The stimulatory effect of TRH or the TRH-analogues on GH secretion was not dose-related.
Thyroid uptake of 201Thallium and its control by TSH
Authors: Maayan Morelly L. , Volpert Eugene M. , Fine Eugene J. , Eisenberg Julius , Lopez Ernesto M. , Dawry Frank P.
Published: December 2008

Patients injected with 201Thallium (201Tl) for myocardial scanning present good thyroid visualization. Determinations in mice injected with 201Tl indicated a high thyroid/serum concentration ratio (T/S). The 201Tl biological half life (t½) in serum (30-135 s) was much shorter than in thyroid (53-55 h) for human subjects and experimental animals. The 1 h 201Tl T/S ratio was comparable to that of 131I and 99m Tc, indicating presence of a gradient for 201Tl also. Increase of endogenous TSH induced by propylthiouracil led to a significant rise in T/S for 99mTc, 131I and 201Tl, whereas TSH inhibition by feeding l-thyroxine led to decrease in T/S for 99mTc and 201Tl. In vitro thyroid/medium concentration ratio (T/M) of 99mTc and 201Tl was decreased after 20' incubation with ouabain, an inhibitor of the Na+,K+, activated ATP-ase. However, perchlorate in vitro or in vivo failed to diminish the 201Tl T/M ratios or to affect the t½ of 201Tl in human subjects, whereas T/M of 201Tl was depressed by KCl addition to the medium.
The effect of insulin-like growth factor (IGF) and of human serum on steps in proteoglycan synthesis
Authors: Silbergeld Avivah , Mamet Rivka , Laron Zvi , Nevo Zvi
Published: December 2008

Embryonic chick pelvic cartilages were incubated in the presence of insulin like growth factor (IGF) (1–100 μU/ml), as well as normal human serum (5%), with radiolabelled precursors of proteoglycan (PG) synthesis: L-[3-3H]serine, D-[6-3H]glucosamine and [35S]Na2SO4. IGF alone (1–15 μU/ml), stimulated in a dose-dependent manner D-[6-3H]glucosamine incorporation into tissue-bound and soluble isolated glycosaminoglycan (GAG) chains. L-[3-3H]serine incorporation into PG molecules was not stimulated by IGF (1–100 μU/ml), despite the increase in the uptake of this precursor into intact cartilage. [35S]Na2SO4 incorporation was unaffected by IGF. Serum promoted the uptake of all three precursors into tissue-bound glycosaminoglycans. It was postulated that IGF could stimulate proteoglycan synthesis not only by elongating existing chondroitin sulphate chains but also by increased synthesis of other sugar chains e.g. keratan sulphate and oligosaccharides.
Corticotrophin stimulation test: inverse correlation between basal serum cortisol and its response to corticotrophin
Authors: Kukreja Subhash C. , Williams Gerald A.
Published: December 2008

Serum cortisol response to synthetic corticotrophin (B1-24-ACTH) was evaluated in 21 normal subjects. There was significant negative correlation (r = −0.633, P < 0.001) between the basal serum cortisol and the increase in serum cortisol level in response to ACTH. Two subjects had an increase in serum cortisol of less than 194 nm/l (7.0 μg/100 ml) and two additional subjects had an increase of less than 278 nm/l (10.0 μg/100 ml). All subjects had an absolute peak value greater than 583 nm/l (21.0 μg/100 ml) at 30 or 60 min post-ACTH. Inverse correlation between basal serum cortisol and the increase in serum cortisol suggests that in patients who have high basal serum cortisol levels, endogenous ACTH may already have reduced the cortisol reserve of the adrenal gland.
Effect of bromocriptine, somatostatin, and oestradiol-17 β on hormone secretion and ultrastructure of human pituitary tumours in vitro
Authors: Prysor-Jones R. A. , Kennedy S.J. , O'Sullivan J. P. , Jenkins J. S.
Published: December 2008

The effect of bromocriptine and somatostatin on hormone secretion and the ultrastructure of human pituitary adenomas was studied in vitro. Prolactin secretion was inhibited by bromocriptine in 3 out of 10 prolactin-secreting tumours and in explants from 2 normal pituitaries. GH secretion was reduced by bromocriptine in 4 out of 6 GH-secreting adenomas but was not affected by the drug in the incubations of normal pituitaries. Somatostatin inhibited GH secretion in 2 out of 5 pituitary adenomas and the effect was comparable with that of bromocriptine. Incubation of prolactin-secreting adenomas with oestradiol for as long as 24 days produced no change in hormone secretion. Examination of tumour explants by electron microscopy showed that somatostatin and bromocriptine produced accumulation of secretion granules but no changes in the secretory organelles. Long term bromocriptine treatment of 'nude' athymic mice bearing xenografts of human pituitary adenomas suppressed hormone secretion and produced some increase in secretion granules but there were no morphological changes in the secretory organelles or other vital structures of the adenoma cells.
The relationships between surgical histometry, outcome and pre-treatment in Graves' disease
Authors: Wilkin T.J. , Gunn A. , Moussa M. Al , Isles T. E. , Crooks J. , Beck J. Swanson
Published: December 2008

Quantitative histometric methods were used to established the relationship between the extent of thyroid lymphocytic infiltration at operation, and outcome exactly 18 months later in 50 surgically-treated Graves' disease patients prepared by carbimazole and triiodothyronine. Periods of pre-operative treatment, surgical technique, histometric analysis and diagnostic criteria were all standardised. Controls (107) were obtained from the forensic laboratory. Thirty-seven patients became euthyroid, but there was no relationship between outcome and epithelial or lymphoid content of the thyroid gland. Neither was there any correlation between the size of lymphoid infiltrate and epithelial mass of the resected thyroids, suggesting that simple lymphocyte infiltrations do not replace thyroid tissue as once thought.

The variation in thyroid epithelial content was nearly 3-fold, so that a surgeon, even if able accurately to judge the anatomical mass of the remnant, would still have little or no idea of its functional mass. The scatter of epithelial content was even greater in glands from patients prepared for surgery by propranolol alone (38 glands, variation × 5.5) or propranolol and iodide (32 glands, variation × 5.9).

Outcome after sub-total thyroidectomy for Graves' disease seems unrelated to the lymphocyte content of the gland and it is questionable to what extent the surgeon can either predict or control the outcome of thyroidectomy in individual Graves' disease patients.
Different effects of oestradiol, oestriol, oestetrol and of oestrone on human breast cancer cells (MCF-7) in long term tissue culture
Authors: Jozan S. , Kreitmann B. , Bayard F.
Published: December 2008

The effects of oestradiol (Oe2), oestrone (Oe1), oestriol (Oe3), oestetrol (Oe4) on the induction of the progesterone receptor (PgR) and growth of MCF-7 cells are compared. All the four oestrogens increase cell PgR concentration. Analysis of the dose-response curves shows induction by Oe2 to be 10 times and 50 times greater than Oe3 and Oe4, respectively. Oe1 and Oe2 are equally effective, even with consideration of metabolic conversion of Oe1 into Oe2. When compared with untreated cells, Oe2, Oe3 and Oe4 do not influence significantly the plating efficiency but all 3 hormones increase thymidine incorporation of cells in log phase growth. Oe2, Oe3 and Oe4 are able to rescue the growth inhibition induced by antioestrogens. The respective potency compared to Oe2 is again in the range of 10 and 50 times lower for Oe3 and Oe4, respectively. On the other hand Oe1 decreases plating efficiency, thymidine incorporation and does not rescue the growth inhibition induced by antioestrogens when the metabolic conversion of Oe1 into Oe2 is prevented. Thus, Oe3 and Oe4 behave like complete Oe2 agonists whereas Oe1 has dissociated effects, agonist on PgR induction and antagonist on cell growth.
Effect of bromocryptine on 20α-hydroxysteroiddehydrogenase regulation in the corpus luteum of the pregnant rat
Authors: Loewit K. , Kofler R. , Tabarelli M. , Schwarz S.
Published: December 2008

Pregnant Sprague Dawley rats were passively immunized with antiserum to bovine luteinizing hormone (anti-LH) on day 10 of pregnancy, and treated with 1 mg/day or 1.5 mg/day of the prolactin (Prl) inhibitor bromocryptine (BEC) between days 10 to 12 or 9 to 12, respectively. On day 12 a laparotomy was performed to assess the state of pregnancy and to remove the ovaries for histochemical detection of 20α-hydroxysteroiddehydrogenase (20α-OHSD) in the corpora lutea of pregnancy. In a second experiment pregnant rats were treated with 1.5mg BEC/day from days 17 to 22, checked for foetal state and ovariectomized on day 22 before giving birth. Treatment with BEC in effective doses did not interfere with anti-LH-induced termination of pregnancy and consequent reappearance of 20α-OHSD activity on day 12, or with spontanenous recurrence of enzyme activity at the end of gestation. It is concluded that Prl has no direct and immediate role in 20α-OHSD regulation, at least on day 12, although substitution by endogenous rat placental lactogen at the end of pregnancy cannot be excluded.
Inherited male pseudohermaphroditism due to gonadotrophin unresponsiveness
Authors: Pérez-Palacios Gregorio , Scaglia Hugo E. , Kofman-Alfaro Susana , Saavedra O. Dolores , Ochoa Sergio , Larraza Oscar , Pérez Ana E.
Published: December 2008

An inherited form of incomplete male pseudohermaphroditism was studied in two post-pubertal and one pre-pubertal sibling. All patients presented a 46XY karyotype, infantile female external genitalia, lack of breast development and sexual hair. Persistently elevated serum levels of gonadotrophins with normal pituitary responsiveness to LRH were found. Serum 17-OH progesterone, androstenedione, and testosterone levels were extremely low before and after gonadal stimulation with hCG. Laparotomy revealed absence of Wolffian and Mullerian derivatives. Testes were small and cryptorchidic. Microscopic and ultrastructural examination revealed seminiferous tubules with absence of spermatogenesis and normal Sertoli cells. The interstitial spaces were mainly occupied by poorly differentiated cells although in the post-pubertal patients there were small and randomly distributed nodules of Leydig cells without crystaloids. Incubation of testicular tissue from one post-pubertal patient with [14C]acetate showed lack of 14C-incorporation into appropriate steroid carriers. These data were interpreted as demonstrating that gonadotrophin resistance was the underlying abnormality of this syndrome, representing the human counterpart of the 'vet' pseudohermaphroditic rat.
The effect of low dose oestrogens on short-term growth and concomitant biochemical phenomena in girls with tall stature
Authors: van den Bosch John S. G. , Smals Anthony G. H. , Kloppenborg Peter W. C. , Valk Ignace M.
Published: December 2008

Using a simple non-invasive ulnar length measuring technique a 70 to 80% decrease in ulnar growth velocity was found during one interval of 9 weeks of low dose ethinyloestradiol administration (0.050 mg daily) in girls with tall stature. This decrease in ulnar growth velocity was found to be statistically significant within 6 and even 3 weeks after starting oestrogen loading whereas the change in body growth velocity was only significant after 9 weeks. After interrupting oestrogen administration, ulnar growth velocities increased again but to values tending to be lower than before ethinyloestradiol loading.

Serum alkaline phosphatase activities and plasma inorganic phosphorus and calcium levels also decreased significantly during oestrogen therapy within 9 weeks. The results found illustrate that the measuring technique used enables evaluation of the short-term effect of hormonal treatment on growth and thereby related biochemical phenomena.
Pituitary apoplexy in acromegaly during bromocriptine therapy
Authors: Yamaji Tohru , Ishibashi Miyuki , Kosaka Kinori , Fukushima Takanori , Hori Tomokatsu , Manaka Shinya , Sano Keiji
Published: December 2008

Two cases of pituitary apoplexy occurring in the course of long-term bromocriptine therapy for active acromegaly are described. Although bromocriptine was effective in lowering serum growth hormone levels and concomitant clinical improvement was achieved, both patients developed an acute episode suggesting pituitary apoplexy when the therapy was continued for 6 and 24 months, respectively. Surgery verified marked haemorrhage and necrosis of an eosinophilic pituitary adenoma in each case. Bromocriptine may have suppressed the growth of these pituitary adenomas resulting in necrosis of the tumour, followed by haemorrhage into the adenoma. Pituitary apoplexy has not been documented as a complication of bromocriptine therapy. This report points out a possible role of bromocriptine in the development of this catastrophe and that careful follow-up is required when long-term treatment with bromocriptine is attempted.
Serum thyroglobulin in differentiated thyroid carcinoma: histological and metastatic classification
Authors: Shah D. H. , Dandekar S. R. , Jeevanram R. K. , Kumar Ajay , Sharma S. M. , Ganatra R. D.
Published: December 2008

Serum thyroglobulin (tg) levels were measured in 112 patients with proved differentiated thyroid carcinoma (6 pre-operative, 32 post-operative and 74 in whom thyroidectomy was followed by radioiodine treatment). The tg levels were within the normal range in patients who had a residual mass in the neck region after surgery and who were in remission. The patients with metastases showed a wide range (undetectable to microgram quantities) of tg in circulation. The analysis of serum tg with respect to histology showed that the follicular variety of carcinoma tends to show higher tg in serum than the papillary type.

Metastatic involvement of bone was associated with much higher serum tg levels than other sites such as lung and lymph node.

Thirteen patients with bone metastases of non-thyroidal primary origin had tg levels within the normal range. Serum tg estimation is useful in excluding thyroid as a primary site in patients with bone metastases of unknown primary origin.
Iodide transport of thyroid plasma membranes
Authors: Endo Y. , Nakagawa H. , Aikawa E. , Ohtaki S.
Published: December 2008

Plasma membranes consisting of closed vesicles were isolated from hog thyroid homogenate. The membrane vesicles showed uphill transport of iodide from an external medium containing monovalent cations, of which K+ induced iodide transport more potently than Na+. The activity of the iodide transport expressed as T/M[I−] was as little as 3 to 11 in the presence of K+, but was invariably present. The ratio reached a maximum within about 10 min and then decreased fairly rapidly to unity. The addition of SCN− or ClO−4 to the external medium inhibited iodide transport. The transport activity was found to be maximum at pH 7.0 to 7.5 in the external medium. A kinetic study showed that the transport rate was saturated with respect to the iodide concentration.

These observations suggested the presence of a carrier-mediated iodide transport system which was coupled with K+ flux across the plasma membrane.
Autoregulation of 3, 3′,5′-triiodothyronine production by rat liver microsomes
Authors: Kaminski T. , Köhrle J. , Ködding R. , Hesch R.-D.
Published: December 2008

Conversion of thyroxine (T4) to 3,3′,5′-triiodothyronine (rT3) was studied in rat liver microsomes. Addition of rT3 at a physiological concentration to the incubation medium inhibited the deiodination of thyroxine to rT3. With a concentration of rT3 greater than 37.6 nM no net rT3 production at pH 8.0 was observed. Further increases in rT3 concentration resulted only in degradation of added rT3 and no net synthesis of rT3 from T4 could be detected. The inhibitory effect of rT3 upon its own production from T4 was pH dependent, 5 fold lower amounts of hormone being required to inhibit completely rT3 production at pH 7.4 than at pH 8.0. With the same experimental conditions no significant effect of rT3 on the conversion of T4 to 3,5,3′-triiodothyronine (T3) could be observed at pH 8.0 with all concentrations of added iodothyronine. A linear production of 3,3′-T2 from added rT3 was determined over the whole range of rT3 concentration, suggesting a lack of saturation of deiodinating enzyme. Binding of rT3 by anti-rT3 antibody added to the incubation mixture enhanced rT3 production from T4 by protecting rT3 from being degraded and/or diminishing the inhibitory effect of this iodothyronine on its own production. It was concluded that rT3 influenced its own production and that this effect may represent an important autoregulatory process in the iodothyronine metabolism.
Virilization of a post-menopausal woman by a testosterone-secreting Leydig cell type adrenal adenoma
Authors: Trost B. N. , Koenig M. P. , Zimmermann A. , Zachmann M. , Müller J.
Published: December 2008

In a 60 year old virilized woman the plasma testosterone concentration was markedly elevated, whereas the plasma cortisol and ACTH as well as urinary 17-ketosteroids, 17-hydroxycorticoids, pregnanetriol and dehydroepiandrosterone were normal. The plasma levels of LH and FSH were in the post-menopausal range. Dexamethasone suppressed the urinary 17-ketosteroids, 17-hydroxycorticoids and pregnanetriol normally, but had no effect upon the plasma testosterone. These findings led to the tentative diagnosis of an ovarian hilus cell tumour. However, bilateral oophorectomy revealed bilateral hyperthecosis without a tumour and did not result in any decrease of the plasma testosterone level. An attempt of adrenal vein catheterization succeeded only on the left side. The lack of a gradient in the testosterone concentration between blood from the left adrenal vein and a peripheral vein prompted a surgical exploration of the right adrenal gland, which led to the discovery and removal of an encapsulated Leydig cell type adenoma, characterized by Reinke's crystalloids. A testosterone concentration gradient between right adrenal and peripheral venous blood obtained intra-operatively, rapid normalization of the plasma testosterone concentration post-operatively, results of a tumour incubation study as well as the clinical outcome proved that this adenoma had been the source of the excessive androgen. A history of a late menarche and persistent menstrual irregularities together with elevated gonadotrophins in spite of excessive testosterone pointed to the possibility of a longstanding gonadotrophin-dependent gonadal cell population in the adrenal, which was fully activated only by the menopausal gonadotrophin rise.
Methacholine, a cholinergic agent, stimulates catecholamine release in man
Authors: Hata Shunichi , Shigetomi Shu-ichi , Fukuchi Soitsu
Published: December 2008

To study the effect of cholinergic stimulation on catecholamine release, methacholine, a choline ester, was injected im into normal subjects.

Significant increases in plasma norpinephrine and plasma epinephrine concentrations were observed in response to methacholine administration with significant haemodynamic changes, but there was no correlation between the rise in plasma catecholamines and the haemodynamic changes.

These results suggest that the increases in plasma catecholamines induced by methacholine did not result from reflex responses to haemodynamic changes and thus could be a direct effect of methacholine on sympathetic nerves and the adrenal medulla.
Local placental influence on the uterine concentration of oestradiol-17β and progesterone in the pregnant guinea-pig
Authors: Batra S. , Thorbert G.
Published: December 2008

Oestradiol-17β (Oe2) and progesterone (P) concentration in the various regions of the uterus, and in ovaries with or without corpora lutea, were determined in the unilaterally pregnant guinea-pig at mid-term and full-term of pregnancy. The concentrations of both Oe2 and P were highest in the non-pregnant horn, and lowest in the perifoetal and juxtaplacental tissue in mid-term and term pregnancies, respectively. The Oe2 concentration in corpus luteum bearing ovaries was much lower than in those without corpora lutea, whereas the P concentration was higher. Ovariectomy performed at term resulted in a decrease of about 40% in plasma P concentration and no significant change in Oe2 concentration. This suggests that there is at least some contribution of P by the ovary even at term of pregnancy. The present data also provide strong evidence for the lack of local placental influence on the concentration of Oe2 and P in the uterus.
Effect of inhibin on rat testicular desoxyribonucleic acid (DNA) synthesis in vivo and in vitro
Authors: Franchimont P. , Croze F. , Demoulin A. , Bologne R. , Hustin J.
Published: December 2008

When injected in vivo 3 h before sacrifice or when incubated in vitro with testicular fragments for 3 h, tritiated thymidine, a reliable index of DNA synthesis and of mitotic activity, was incorporated into the DNA of differentiated spermatogonia, as shown by autohistoradiography. The maximum DNA specific activity was obtained in pubertal rats aged 42 days, weight 150 g. Two preparations of inhibin extracted from ram rete testis fluid (RTF) of different molecular weight (> 10 000 for RTF1 and < 5000 for RTF3) but which possess the same biological properties were investigated for their effect on thymidine uptake in vivo and in vitro. In vivo both preparations specifically inhibited tritiated thymidine incorporation into testicular DNA of pubertal animals (42 days). No change in thymidine uptake into hepatic DNA was observed. Tritiated thymidine incorporation into testicular DNA was lower in normal adult rats and in hypophysectomized pubertal animals. RTF1 and RTF3 did not affect thymidine incorporation in either case. The reasons for this lack of effect are discussed. In vitro, both preparations induced a dose-dependent decrease in DNA synthesis in testis fragments from rats aged 42 and 49 days. The preparations lost their in vivo and in vitro inhibitory effects when denatured by heating and trypsin digestion. The inhibin preparations probably reduced testicular DNA synthesis and spermatogonial multiplication by reducing FSH secretion in vivo but also had a direct effect on the germ cells as shown by the in vitro experiments. These in vivo and in vitro actions of inhibin preparations are similar to those of the testicular chalones. The relationship which might exist between inhibin and the chalones is discussed.