bluuebunny/crossref_metadata_2025 huggingface dataset:
Appraisal of endocrine function of segmental autotransplanted pancreas in dogs
Authors: Jonung M. , Berlatzky Y. , Chen M.-H. , Munda R. , Banks I. G. , Brackett K. , Murphy R. F. , Joffe S. N.
Published: December 2008

Abstract. There is increasing interest in pancreatic transplantation for patients with diabetes. In experimental models, endocrine function is usually monitored by determination of insulin and glucose levels in plasma. In this study following a segmental pancreatic autotransplant to the iliac fossa in dogs, a combined analysis of three pancreatic islet hormones, insulin, pancreatic polypeptide (PP) and glucagon was undertaken by radioimmunoassay of plasma. These were measured under basal conditions and following provocation with a standard meal, arginine, secretin and bombesin infusions. Immunohistochemical and electron microscopic examination of transplanted tissue was also performed.

Circulating insulin and glucose levels in the surviving dogs with transplants reflected normoglycaemia with a normal tolerance to iv glucose and immunohistochemical detection of endocrine cells producing insulin, PP and glucagon. Secretory granules were found in A and B cells by electron microscopy. The normal circulating glucagon immunoreactivity could have originated in gastric antral A cells as well as in pancreatic tissue. It was not possible, however, to stimulate the autotransplanted pancreas to release detectable PP into the circulation.
Effect of gonadotrophin releasing hormone upon the pattern of steroidogenesis in isolated preovulatory rat follicles
Authors: Hillensjö Torbjörn , Ekholm Carl , Hedin Lars
Published: December 2008

Abstract. The effects of GnRH and a potent GnRH analogue (D-Ala6-des-gly-NH2-GnRH-ethylamide) on steroidogenesis in isolated preovulatory follicles of PMSG-treated immature rats were examined in short-term incubations and compared to the effect of LH. Steroids were analyzed by RIA. GnRH stimulated the accumulation of pregnenolone (2-fold), progesterone (4-fold), 20α-OH-progesterone (38-fold), androstenedione (4-fold), testosterone (3-fold), and oestradiol-17β (2-fold) during a 6 h incubation. The time-course of stimulation was the same for each of the steroids analyzed, with a significant effect at 4 and 6 h, but not at 2 h of incubation. Dose-response curves were similar for each steroid, and the GnRH analogue and GnRH gave parallel curves with minimal effective concentrations being 1 and 10 ng/ml, respectively. The stimulatory effect of LH was more pronounced and rapid (2 h) than that of GnRH. During prolonged incubation (6–8 h) with GnRH or LH there was evidence for an inhibition of testosterone production, probably due to suppression of the C21-side chain cleavage enzyme. Thus, the qualitative response to GnRH on follicular steroidogenesis resembled that of LH in some but not all respects. The differences in time-course and maximal steroid secretion between GnRH and LH are compatible with different mechanisms of action in the follicle.
A case of Klinefelter's syndrome with acquired hypopituitarism
Authors: Maisey D. N. , Mills I. H. , Middleton H. , Williams I. G.
Published: December 2008

Abstract. The association of Klinefelter's syndrome (KS) and hypopituitarism has been described in previous isolated case reports, in most of which the hypopituitarism was partial. A case is described of a man with KS who acquired hypopituitarism in adult life. The diagnosis of KS was made at the age of 25 years on standard laboratory tests when he presented with failure of ejaculation and typical clinical features. Thirteen years later he presented with anaemia and further regression of secondary sexual characteristics. All aspects of anterior pituitary function were abnormal. The cause of the hypopituitarism was not determined, but may have been post-traumatic.
The effect of D-Trp6-LRH upon secretion of gonadotrophin – a possible therapeutic application in anorexia nervosa
Authors: Zgliczyński S. , Baranowska B. , Jeske W. , Niewiadomska A. , Rozbicka G. , Schally A. V.
Published: December 2008

Abstract. The aim of this study was to evaluate the effect of the agonistic LRH analogue (D-Trp6-LRH) on LH, FSH and prolactin secretion, and its possible efficacy in female patients with anorexia nervosa. The study included 18 female patients with anorexia nervosa and 7 healthy women in the same age group. The patients with anorexia nervosa were divided into two groups of 9 women each. The first group consisted of patients in the weight loss phase of the disorder and the second of 9 women who had achieved normal body weight. Additionally, in 6 women with anorexia nervosa serum LH concentration was determined in response to native LRH before and 14 days after the treatment with D-Trp6-LRH.

Serum LH, FSH, prolactin concentrations were determined before and 5, 10, 24 and 48 h after administration of D-Trp6-LRH in a dose of 5 μg. The serum LH response to D-Trp6-LRH in the second group did not differ from that of the control group. However, in women with anorexia nervosa in the weight loss phase, LH release in response to administration of the analogue was significantly lower. FSH release after LRH analogue administration in both groups of patients with anorexia nervosa did not differ from that in the control group. The increased LH secretion in response to native LRH after treatment indicates that D-Trp6-LRH in low doses did not inhibit pituitary responsiveness. A dose of 5 μg of D-Trp6-LRH was administered in a therapeutic regimen every 48 h from 1 to 3 months to 7 of 9 patients with anorexia nervosa who exhibited amenorrhoea in spite of normalization of body weight.

All the patients treated with the analogue resumed menstruation. The results of this study suggest that D-Trp6-LRH may be of value in the treatment of amenorrhoea in women with anorexia nervosa.
Testosterone-induced hyperprolactinaemia in a patient with a disturbance of hypothalamo-pituitary regulation
Authors: Nicoletti I. , Filipponi P. , Fedeli L. , Ambrosi F. , Gregorini G. , Santeusanio F.
Published: December 2008

Abstract. A case of a patient with hypopituitarism due to a disturbance of hypothalamo-pituitary regulation is presented, who developed high-grade hyperprolactinaemia after the initiation of substitutive therapy with testosterone esthers.

The increase in serum Prl was strictly related to testosterone aromatization to oestradiol, since anti-oestrogen compounds were effective in reducing (clomiphene) or abolishing (tamoxifen) the enhanced Prl secretion. The oestrogen effect in raising Prl release was not attributable to a reduction in the dopamine inhibition of Prl-secreting cells, as the dopamine-antagonist domperidone failed to increase Prl serum levels in the same patient.

This suggests that, in man, the oestrogen effect in enhancing Prl release is mainly enacted directly on the pituitary lactotrophs rather than exerted through a reduction in the hypothalamic dopamine activity.
Long-term alprenolol treatment affects serum T4, T3 and rT3 in euthyroid patients with ischaemic heart disease
Authors: Perrild H. , Pedersen F. , Rasmussen S. L. , Jürgensen H. J. , Skovsted L.
Published: December 2008

Abstract. After treatment with alprenolol for 1 year, serum 3,3',5'-triiodothyronine (rT3) was significantly increased (P < 0.01) in a group (n = 20) of euthyroid subjects compared to a control group (n = 20) given placebo. All subjects had definite or suspected myocardial infarction one year previously. Serum thyroxine (T4), free T3 index (FT4I), serum 3,5,3'-triiodothyronine, (T3) and free T3 index (FT3I) were not significantly different in the two groups. Alprenolol and placebo were gradually withdrawn over 14 days. On the first day after withdrawal a significant decrease in serum rT3 in the alprenolol treated group was the only change observed. Fourteen days after withdrawal a significant fall in serum T4, FT4I, rT3 and a rise in serum T3 and FT3I was found in the alprenolol treated group. Six months after withdrawal the only further change observed in the alprenolol treated group was an increase in T3 and FT3I. No changes occurred in the placebo treated group in any of the hormones studied. The results are consistent with a direct effect of long-term alprenolol treatment on the peripheral levels of serum T4, T3 and rT3 in euthyroid subjects. The changes in the thyroid hormones after withdrawal further indicate withdrawal of a permanent inhibition of 5'deiodinase during long-term treatment with alprenolol in euthyroid subjects.
Rapid adaptations of serum thyrotrophin, triiodothyronine and reverse triiodothyronine levels to short-term starvation and refeeding
Authors: Hugues Jean-Noel , Burger Albert G. , Pekary A. Eugene , Hershman Jerome M.
Published: December 2008

Abstract. Nutrition influences thyroid function at the level of TSH secretion, at the level of monodeiodination, and possibly elsewhere. In order to study the effect of starvation on TSH secretion, 8 healthy male volunteers fasted for 30 h and were then refed with 800 kcal. Refeeding was performed at 19.00 h and blood was sampled at 20 min intervals until midnight. Control experiments were performed in the same subjects both when they were normally fed and when the starvation period was prolonged a further 5 h until midnight. Starvation decreased serum TSH levels to below 1 mU/l, and without refeeding the nocturnal peak of the TSH nycthemeral rhythm was abolished. With refeeding serum TSH tended to increase towards midnight and was significantly higher than during starvation. However, the serum TSH levels remained significantly below those at the same time of the day in the absence of a preceding starvation period.

Serum T3 levels were significantly lower than in the fed state. The mean values were 1.84 ± 0.03 vs 2.30 ± 0.06 nmol/l (120 ±2 vs 150 ± 4 ng/100 ml, mean ± sem P < 0.01). Refeeding did not result in a measurable change in serum T3 concentration (1.80 ± 0.05 nmol/l; 120 ± 3 ng/100 ml, mean ± sem, n.s.). The contrary was true for rT3 levels which increased in starvation and tended to fall with refeeding, but this decrease was not significant.

As glucocorticoids have been implicated in the control of monodeiodination and TSH secretion, serum cortisol levels were also measured. They did not differ during the 3 experimental periods. The results show that short-term starvation and refeeding may be a valuable tool for studying in vivo control of TSH secretion.

The results show that short-term starvation and refeeding may be a valuable tool for studying in vivo control of TSH secretion.
Plasma responses of pancreatic polypeptide, glucagon and insulin in normal and alloxan diabetic dogs, and their regional levels in the pancreas
Authors: Tasaka Yoshimasa , Inoue Sachiko , Marumo Koji , Hirata Yukimasa
Published: December 2008

Abstract. The plasma responses of pancreatic polypeptide (PP), glucagon (IRG) and insulin (IRI) after administration of beef soup were studied in normal and alloxan diabetic dogs kept in a poor metabolic state for 4 weeks, and their regional levels in the pancreas were determined and compared at the uncinate process, head, body and tail. The plasma PP levels of the diabetic dogs were significantly higher than those of the normal dogs and they increased after beef soup administration in both groups. The plasma IRG levels did not change significantly after beef soup administration in either group, but significantly high levels were found in the diabetic dogs. The IRI content in the normal dog pancreas was highest at the tail, followed in order by the body, head and uncinate process, and was decreased to about one-tenth to one-fortieth in the alloxan diabetic dogs. On the other hand, the amounts of PP in the pancreas of both normal and diabetic dogs were greatest at the uncinate process, followed in order by the head, body and tail. In an inverse relationship with the PP findings, the IRG content in the pancreas was highest at the tail and lowest at the uncinate process in both kinds of dogs. The differences in both PP and IRG between diabetic and normal dogs were generally not significant. These results show that irrespective of the high plasma levels of PP and IRG in the diabetic dogs, their levels in the pancreas did not change significantly.
Fluctuations in the number of germ cells during the late foetal and early postnatal periods in boys
Authors: Müller Jørn , Skakkebæk Niels E.
Published: December 2008

Abstract. Previous studies have shown marked elevations of serum concentrations of follicle stimulating hormone, luteinizing hormone, and testosterone during the first 6 months of life in boys. We have carried out a quantitative study of the changes in the total number of germ cells in 46 pairs of autopsy testes from normal boys between 28 weeks of gestation and 1000 days of postnatal life. The study demonstrated an increase in the total number of germ cells in boys up to 100 days of age (Spearman rho = 0.62, P < 0.01), and a successive decrease in boys older than this age (Spearman rho = −0.56, P < 0.01). Thus a peak in the total number of germ cells per boy was found somewhere between day 50 and 150 after birth, and the course of this variable was similar to that previously reported on the hormonal concentrations in serum.
Insulin-like growth factor I in the dog: a study in different dog breeds and in dogs with growth hormone elevation
Authors: Eigenmann J. E. , Patterson D. F. , Zapf J. , Froesch E. R.
Published: December 2008

Abstract. A radioimmunoassay (RIA) devised for the measurement of human insulin-like growth factor I (IGF I) was employed for the measurement of canine IGF I. Canine IGF I was extracted from plasma specimens by gel chromatography. Columns were eluted with 1 m acetic acid and the fractions representing the 55 to 85% bed volume were pooled, lyophilized and reconstituted with assay buffer. Serial dilutions of canine IGF I from both normal and acromegalic dogs when added to the RIA system gave a similar displacement pattern of human [125I]IGF I as the one obtained by the addition of unlabelled human IGF I. The dose-response curve obtained by canine IGF I paralleled the one obtained by human IGF I. Logit-log transformation and least squares fitting resulted in straight line fitting of the standard curve between 0.039 and 5 ng IGF I added per tube. The within-assay coefficient of variation (CV) was 16.7% and the between-assay CV was 21.8%. Plasma IGF I concentrations in normal dogs appeared to be a function of body size. The concentrations were 36 ± 27 ng/ml in Cocker Spaniels, 87 ± 33 ng/ml in Beagles, 117 ± 34 ng/ml in Keeshonds, and 280 ± 23 ng/ml in German Shepherds (mean ± sem). The mean IGF I level in a group of dogs with growth hormone (GH) elevation was 700 ± 90 ng/ml. Though this group of dogs comprised both small and large dogs, the mean IGF I level significantly differed from the one found in German Shepherds, the largest breed studied (P < 0.01). IGF I levels in dogs with GH elevation were similarly elevated in both dogs exhibiting acromegaly and dogs exhibiting GH-diabetes, but no signs of acromegaly. In dogs with GH elevation, drop in GH levels was associated with a significant drop in IGF I levels.
The role of inhibin in adult male rats: the effect of inhibin deficiency and androgen antagonism on serum and pituitary gonadotrophins
Authors: Lipner H. , Dhanarajan Pushparani
Published: December 2008

Abstract. We examined the ability of inhibin-F contained in porcine follicular fluid (pFF) to regulate serum gonadotrophins in male rats made deficient in endogenous inhibin and unable to respond to normal endogenous androgen levels. Efferent duct ligation (EDL) effected endogenous inhibin deficiency and the anti-androgen flutamide (F) (13.4 mg/dose, sc once per day) raised the set point for androgen control of the hypothalamus to a level intermediate between the intact and castrate serum gonadotrophin levels. EDL, F and EDL + F caused serum FSH levels to rise and administration of pFF (2 ml per day) suppressed the elevated serum FSH levels of these experimental models to intact animal levels. Though EDL had no effect on serum LH, F increased the serum LH levels and EDL plus F increased them further. Treatment with pFF suppressed the serum LH to intact levels. EDL rats had slightly increased serum androgen (6 ng/ml) but F and EDL + F treated rats had very greatly increased serum androgen concentrations (22 and 32 ng/ml, respectively) which treatment with pFF suppressed to intact levels. Pituitary FSH was increased by EDL and LH was increased by F. In both cases, the increased pituitary gonadotrophins were suppressed by treatment with pFF. We conclude that inhibin regulates synthesis and secretion of FSH and secretion of LH.
The response of plasma arginine vasopressin to 14 h water deprivation in the elderly
Authors: Li Ching Huai , Hsieh Shao Ming , Nagai Isamu
Published: December 2008

Abstract. The response of plasma arginine vasopressin (AVP) to 14 h water deprivation was investigated in 30 healthy elderly individuals ranging in age from 63 to 87 years, with a mean age of 76.5 years.

The mean AVP concentrations, both at normal hydration and after the water deprivation test, were significantly lower than those in the young. Moreover, the post-test mean value of Uosm/Posm in the elderly increased up to 1.55 ± 0.52, which is lower than that in the young in whom the value was greater than 2.

These results suggest that the aged are prone to incomplete diabetes insipidus. This pathological state might predispose to electrolyte imbalance in the elderly.
Post-parathyroidectomy restoration of normal calcium homeostasis in neonatal primary hyperparathyroidism
Authors: Ch'ng J. L. C. , Kaiser A. , Lynn J. , Joplin G. F.
Published: December 2008

Abstract. Total parathyroidectomy is required to cure neonatal primary hyperparathyroidism (NPH) as any parathyroid remnant quickly becomes hyperplastic, causing recurrent hypercalcaemia. We present a patient with NPH who had total removal of his eutopic parathyroid glands but continued to have parathyroid hormone secretion from presumed ectopic parathyroid tissue. Hypercalcaemia initially recurred but normal calcium homeostasis was established as the child grew older. We postulate that the underlying defect in NPH is decreased sensitivity to the serum ionic calcium feedback inhibition at the parathyroid receptor level and that this sensitivity can improve with age.
Effects of some hydroxylated sterols on the steroid production in isolated rat adrenal glomerulosa and fasciculata/reticularis cells in the presence of potassium, angiotensin II or ACTH
Authors: Huijmans J. G. M. , Falke H. E. , Degenhart H.J.
Published: December 2008

Abstract. 22S-OH-cholesterol and 25-OH-cholesterol are good aldosterone precursors in isolated rat adrenal glomerulosa cells. In the two concentrations tested (25 and 50 μm) 25-OH-cholesterol stimulated the aldosterone production in a (not-linear) dose-dependent way. An increase in the 22S-OH-cholesterol concentration from 25 μm to 50 μm led to a decrease in the aldosterone production.

The exogenous substrate deoxycorticosterone, entering the steroidogenic pathway after the cholesterol side-chain cleavage, is a much better substrate than the sterols mentioned. These results suggest that the cholesterol side-chain cleavage is the rate-limiting step in the aldosterone production from both sterols.

We found no effect of the sterols on the potassiuminduced aldosterone synthesis. This might be explained by the existence of separate pools of steroid intermediates within the adrenal cell.

In vitro a difference in steroid production rates exists between glomerulosa and fasciculata/reticularis cells. This may arise from differences in availability of endogenous steroid precursors like cholesterol. However similar differences can be observed if exogenous substrates like 25-OH-cholesterol or 22S-OH-cholesterol are used. These results therefore suggest that enzymatic activities in the steroidogenic pathway are more important than the cholesterol concentration in regulating steroid production in isolated rat adrenal glomerulosa and fasciculata/reticularis cells.
Renin-angiotensin system in hypothyroid rats: effects of potassium iodide and triiodo-L-thyronine
Authors: Jiménez E. , Montiel M. , Narváez J. A. , Morell M.
Published: December 2008

Abstract. Kinetic studies of the renin-angiotensin system (RAS) were carried out by measuring plasma renin activity (PRA), plasma renin concentration (PRC) and plasma renin substrate (PRS). Changes in this system were studied during hypothyroidism, after administration of propylthiouracil (PTU), and in thyroidectomized rats. A significant decrease in PRA and PRC was observed in those animals previously treated with PTU. However, a significant increase in PRC, and a decrease in PRS, were found in T animals, but no changes in PRA were observed. In these animals, after daily administration of potassium iodide for I week (T+KI), no changes in RAS were observed in comparison with T rats. Nevertheless, administration of daily doses of triiodo-ithyronine (T+T3) induced a significant increase in PRA, leaving PRC unaltered. In this case the changes in PRA were related to the increase in PRS after T3 treatment. These results suggest that two different mechanisms were involved in renin release, one activated in T rats and the other in pharmacological hypothyroidism.
Metabolic effects of physical exercise in insulin-dependent diabetics controlled by continuous subcutaneous insulin infusion or conventional injection therapy
Authors: Viberti G. C. , Home P. D. , Bilous R. W. , Alberti K. G. M. M. , Dalton N. , Keen H. , Pickup J. C.
Published: December 2008

Abstract. The metabolic and hormonal response to moderately severe exercise 2 h after breakfast was assessed in 8 insulin-dependent diabetics during conventional insulin injection therapy and after 3 weeks of continuous sc insulin infusion.

Blood glucose fell from 12.1 to 4.4 mmol/l on injection therapy; this was accompanied by a significant rise (P < 0.05) in free insulin to 57 mU/l. On infusion therapy plasma glucose fell and stabilised at 3.6 mmol/l from pre-exercise levels of 7.1 mmol/l, while free insulin level was unchanged at the end of the exercise period (31 mU/l). The fall in blood glucose on injection therapy was accompanied by an exaggerated growth hormone response to exercise that was normalised by 3 weeks of infusion therapy. Basal and post-prandial levels of intermediary metabolites, catecholamines and glucagon were comparable on the two insulin regimens. Responses during exercise were generally similar and no different from those of normal subjects, with the exception of plasma NEFA levels which became abnormally suppressed. Good metabolic control of diabetes is thus accompanied by nearly normal hormonal and metabolic response to moderately severe exercise.
Influence of progesterone, androstenedione and oestradiol-17β on the incorporation of [3H]proline in the human follicular wall
Authors: Tjugum Jostein , Dennefors Bo , Norström Anders
Published: December 2008

Abstract. The incorporation of proline, a precursor for collagen specific hydroxyproline, is regarded to reflect the metabolism of collagen. In vitro experiments were carried out to investigate the influence of sex steroids on the incorporation of [3H]proline into the human follicular wall. Tissue pieces from the apical wall of follicles at different stages of development were incubated in the presence of the steroids and [3H]proline, and the tissue bound radioactivity was determined.

Progesterone induced a decrease of radiolabelling in both unripe and pre-ovulatory follicles. Androstenedione caused a similar effect but only in pre-ovulatory follicles. The influence of oestradiol-17β on the incorporation of [3H]proline was less pronounced with a tendency towards a decrease of radiolabelling in both types of follicles.

It is suggested that the observed biochemical changes induced by sex steroids are of importance for connective tissue remodelling preceding human follicular rupture.
Immunoreactive calcitonin content in foetal thyroid glands and in placentae of rats
Authors: Jarzab Barbara , Kokot Franciszek , Bafdys Agata
Published: December 2008

Abstract. Immunoreactive calcitonin (I-CT) was assayed in rat thyroid glands from foetuses with a gestational age of 15.5–22 days. The mean content of the hormone was 455.0 ± 35.8 ng/gland. A positive linear correlation was found between the I-CT content in the thyroid glands and the gestational age of the foetuses. I-CT was also present in rat placentae from 10.5–21.5 days old pregnancies. A mean placental concentration of 4.5 ± 1.2 ng I-CT/mg wet tissue was found. The highest hormone concentrations were observed in placentae from 10.5 day old foetuses, displaying a progressive fall during the further course of pregnancy. It is concluded that the rat foetal thyroid gland produces I-CT beginning from a gestational age of 15.5 days'. The need for further investigations into a possible role of CT in transplacental calcium transport is also indicated.
Effect of the vasopressin antagonist d/CH2/5Tyr/Et/VAVP on the antidiuretic action of exogenous and endogenous vasopressin
Authors: László F. A. , Csáti S. , Baláspiri L.
Published: December 2008

Abstract. The effect of [1-(β-mercapto-β,β-cyclopentamethylene-propionic acid),2-0-ethyltyrosine,4-valine]-arginine vasopressin on the water metabolism was studied in rats. The compound decreases the antidiuretic action of exogenous vasopressin in Brattleboro rats; in rats without diabetes insipidus it causes temporary polyuria and eliminates the response of antidiuresis to an osmotic stimulus. The results indicate that this compound can block the antidiuretic action of both exogenous and endogenous vasopressin.
Prevention of hyponatraemia and cerebral oedema by the vasopressin antagonist d/CH2/5Tyr/Et/VAVP in rats treated with pitressin tannate
Authors: László F. A. , Csáti S. , Baláspiri L.
Published: December 2008

Abstract. A rat model of the Schwartz-Bartter syndrome was created by the administration of a high dose of a long-acting vasopressin preparation (pitressin tannate) together with a forced water intake. The treatment led to water retention, hypernatriuria, marked hyponatraemia (in 4–5 days) and severe cerebral oedema. These changes could be prevented by the simultaneous administration of [1-(β-mercapto-β,β-cyclopentamethylene-propionic acid),2-0-ethyltyrosine,4-valine]arginine vasopressin. The observations indicate that this vasopressin antagonist analogue might be of use in the future as an effective drug against the Schwartz-Bartter syndrome.
Isolation of thyroid stimulating immunoglobulins by affinity chromatography using protein A sepharose
Authors: Kjærulff Henrik , Bech Karine , Bliddal Henning
Published: December 2008

Abstract. Sera from a reference pool, 29 controls and 18 patients with Graves' disease were fractionated on sepharose CL-4B protein A. After a primary elution of the unbound fraction at normal pH, IgG subclasses 1, 2 and 4 were eluted using a discontinuous pH gradient. The eluate was monitored by UV-absorption at 280 nm and three peaks were observed within narrow pH ranges in all sera tested. From the reference pool (n = 10) peak A was eluted at pH 6.6 ±0.1. peak B at 4.2 ± 0.03 and peak C at 3.8 ± 0.01. This distribution was partially related to the IgG subclasses with IgG1 recovered in peak C, while IgG2 and IgG4 were distributed in both peak B and C.

Thyroid adenylate cyclase stimulating antibodies (TSAb) and thyrotrophin binding inhibiting immunoglobulins (TBII) were measured in the pooled fractions under these peaks. In the reference pool total assay variations (sd) were 10–22 per cent. The 95 percentiles of the 29 control values were used as reference range. In the 18 patients TSAb were positive in 4 in fraction A, 9 in B and 12 in C. TBII were found in one in fraction A, none in B and 13 in C. No correlation between TSAb and TBII values were found before or after fractionation. In most cases TSAb activity was highest in fraction C, however, in 3 patients fraction A was the more active and in these patients TBII were only found in fraction C.

It is concluded, that the present results indicate a heterogeneity of the thyroid stimulating immunoglobulins with separation of the TSAb and TBII activities in some patients.
Decreased T4 to T3 conversion in tissues of streptozotocin-diabetic rats
Authors: Ortiz-Caro J. , Obregón M. J. , Pascual A. , Jolin T. , González M.
Published: December 2008

Abstract. The effect of experimental diabetes on T4 to T3 conversion, T3-deiodination, and the pituitary response to a dose of T4 and T3 was studied. Pituitary GH and plasma TSH were determined as a measure of the biological response to thyroid hormones. Thyroidectomized rats, 5 days after injection with saline or streptozotocin (thyroidectomized-control (Th.C) and thyroidectomized-diabetic (Th.D) rats, respectively) received an ip dose of T4 + [125I]T4 or T3 + [125I]T3. Rats from each group were sacrificed at varying intervals after thyroid hormone injection. Th.D rats had hyperglycaemia, glycosuria, and a body weight of about 80% of that of Th.C rats. The concentrations of [125I]T4 and [125I]T3 were measured in several tissues after ethanol extraction, separation by thin-layer chromatography, and identification with markers. Plasma TSH and pituitary GH were measured by specific RIAs. Diabetes decreased the conversion of T4 to T3 in several tissues, including the pituitary, but did not affect the deiodination of T3. The decrease in pituitary T3 content after a dose of T4 was accompanied by a diminution of the biological effect of the T4 dose on pituitary GH. Since diabetes also interferes with this biological response to a T3 dose, it seems likely that the reduced biological effect of thyroid hormones on pituitary GH may be related to an alteration in the somatotrophin T3 receptors, or in post-receptor events. Moreover, the data indicate that although T3 generation in the pituitary was reduced, the same dose of T4 had a greater inhibitory effect on TSH secretion in Th.D rats than in Th.C rats. These results do not support the possibility that increased local pituitary T4 to T3 conversion mediates the decrease in circulating TSH levels observed in Th.D animals. The apparent increase of the effectiveness of the T4 dose on TSH release may be related to a diminution of pituitary TRH control.
Calcitonin in hepatoma and cirrhosis
Authors: Conte Nicola , Cecchettin Maurizio , Manente Paolo , Valmachino Guido , Roiter Ignazio , Pavan Pierantonio
Published: December 2008

Abstract. Plasma immunoreactive calcitonin (iCT) is elevated in primary liver cancer and its measurement has been proposed as a tumour marker. Since iCT is also frequently raised in alcoholic liver cirrhosis, it would be of practical relevance to distinguish this condition from primary hepatoma by measuring the plasma level of iCT. We measured plasma iCT levels in 23 subjects with primary liver cancer, in 27 with hepatic cirrhosis and in 42 healthy subjects who served as normal controls. A gel-chromatograpy analysis was carried out on the plasma of two cases of hepatoma, two of cancer and cirrhosis, and two of alcoholic liver cirrhosis.

The subjects with primary liver cancer had values of plasma iCT (pg/ml; mean ± se) of 342 ± 41; those with liver cirrhosis 159 ± 22, and normal controls 73 ± 3. The increase in primary liver cancer was significant in comparison both healthy subjects (P < 0.001) and with cirrhotic patients (P < 0.001). Twenty-two out of 23 patients with primary liver cancer and 13 out of 27 with liver cirrhosis had elevated iCT values (upper normal limit 113 pg/ml). There was no significant difference between plasma iCT values of patients with cancer and those with cirrhosis. However, we measured iCT values higher than 400 pg/ml only in patients with primary liver cancer. The gel-filtration analysis showed 3 or 4 peaks of iCT with a molecular weight higher than synthetic human calcitonin.

The results suggest that plasma iCT levels can be considered a reliable marker of liver cancer, whereas its discriminating power between liver cancer and cirrhosis was not entirely satisfactory.

The increase of plasma iCT in hepatoma and in alcoholic cirrhosis is related to the presence of macromolecular forms of calcitonin. The pathogenesis and meaning of large forms of iCT are unexplained.
Patterns of plasma melatonin with ageing and mental condition: stability of nyctohemeral rhythms and differences in seasonal variations
Authors: Touitou Yvan , Fèvre Michèle , Bogdan Andrè , Reinberg Alain , De Prins Jean , Beck Hervé , Touitou Catherine
Published: December 2008

Abstract. Effects of ageing and mental condition on the nyctohemeral and seasonal rhythms of plasma melatonin in human subjects were investigated. Four groups of subjects were formed for a transverse study: 7 healthy young men (24 years), 6 elderly women, 6 elderly men and 6 elderly patients (2 men and 4 women) suffering from senile dementia (70–80 years). The subjects were synchronized. Blood samples were taken every 4 h during 24 h in January, March, June and October. In comparison to young men, the plasma levels of melatonin were markedly decreased (by about one half) in elderly subjects without any difference according to sex or mental condition. Nyctohemeral rhythms of the hormone were validated in all groups and at all sampling sessions. The nyctohemeral acrophases were remarkably stable (around 03.00 h) whatever the season, age or sex. A seasonal variation was found in all groups (except elderly women) with differences between young and elderly subjects: plasma melatonin levels were significantly lower in January than in June in young men, whereas in elderly subjects they were significantly lower in October than in January/March. No significant difference was observed in mesor, amplitude or acrophase of nyctohemeral and seasonal rhythms of plasma melatonin in patients with senile dementia when compared with healthy elderly subjects. The stability of the nyctohemeral peak time whatever the age group or season as opposed to the differences in the seasonal pattern of plasma melatonin according to the age groups raises the problems of both outdoor photoperiod and ageing in ruling the secretion of melatonin in man.
In vivo and in vitro comparisons of biological activities of bovine, ovine and rat CRF (corticotrophin-releasing factor)
Authors: Yasuda Naoki , Yasuda Yuko , Aizawa Toru , Maruta Sakae , Greer Monte A.
Published: December 2008

Abstract. The biological activity of partially purified bovine hypothalamic CRF (corticotrophin-relasing factor) was compared to those of synthetic CRFs (ovine, rat) sauvagine and vasopressin in vivo and in vitro. ACTHprimed hypophysectomized rats with heterotopically transplanted pituitaries and medial basal hypothalamic ablation (H-T + MBHA), and intact rats pre-treated with chlorpromazine, morphine and Nembutal (C-M-N) were used for in vivo CRF assays. Perifused rat adenohypophyseal fragments were employed for in vitro studies. CRF-A (void volume fractions, 'big' CRF) and CRF-B (Kav = 0.583) purified from bovine hypophyseal stalk, synthetic ovine and rat CRF, and sauvagine all induced significant stimulation of ACTH and/or corticosterone secretion in these systems. Synthetic ovine and rat CRF and sauvagine showed comparable CRF potency. The CRF dose-response slopes for bovine CRF were somewhat steeper than those for ovine CRF or sauvagine in the in vitro system. Vasopressin had the least steep dose-response slope. Intravenous bolus administration of ovine CRF caused a more prolonged (>20 min) elevation of plasma ACTH compared to a relatively short duration after bovine CRF-A. These data suggest that bovine hypothalamus contains substance(s) which exhibits different CRF characteristics from those of ovine CRF.
Changes in plasma GH levels and clinical activity during bromocriptine therapy in acromegaly. The value of predictive tests
Authors: Nortier J. W. R. , Croughs R. J. M. , Donker G. H. , Thijssen J. H. H. , Schwarz F.
Published: December 2008

Abstract. Twenty-seven patients with active acromegaly despite previous treatment by surgery and/or radiotherapy received bromocriptine in a dose of 10–20 mg daily for a period of 6–9 months. The results of chronic bromocriptine treatment were evaluated by measurement of plasma growth hormone (GH) levels during the day and by subjective and objective criteria of clinical activity. The results of chronic bromocriptine treatment were also compared with four biochemical criteria obtained before treatment e.g. basal plasma prolactin (Prl) levels and the plasma GH response to oral administration of 2.5 mg bromocriptine respectively iv administration of 200 μg TRH and 500 μg somatostatin. The main observations may be summarized as follows: 1) The mean pre-treatment GH levels during the day ranged from 6–207 mU/l. Hyperprolactinaemia was present in 6 patients. 2) During bromocriptine treatment mean plasma GH levels decreased to less than 50% in 11 patients (GH responders) whereas in 19 patients changes of mean plasma GH and of subjective criteria of clinical activity were concordant. 3) Glucose tolerance improved significantly (P < 0.01) in 10 GH-responders and the urinary hydroxyproline/creatinine ratio decreased significantly (P < 0.05) in 8 GH-responders. 4) Five out of 6 patients with hyperprolactinaemia belonged to the group of GHresponders. 5) A single dose of 2.5 mg bromocriptine induced a more than 50% decrease of plasma GH in 8 of 11 GH-responders and in 5 of 16 GH non-responders. 6) The iv injection of 200 μg TRH was followed by a rise of plasma GH of more than 100% in 9 of 11 GHresponders and in 6 of 16 non-responders. 7) Responsiveness to both a single dose of bromocriptine and TRH was found in 8 of 11 GH-responders and in 3 of 16 GH non-responders.

Conclusions

Bromocriptine is effective as adjunctive therapy when active acromegaly persists after treatment with surgery and/or radiotherapy.

In general, a good correlation is found between GH responsiveness and subjective and objective criteria of clinical activity during bromocriptine treatment.

Hyperprolactinaemia predicts GH responsiveness to chronic bromocriptine treatment with high specificity.

The combination of a bromocriptine test and a TRH test are of best predictive value with respect to the results of chronic bromocriptine therapy in normoprolactinaemic acromegalics.
Altered parathyroid set point to calcium in familial hypocalciuric hypercalcaemia
Authors: Auwerx J. , Demedts M. , Bouillon R.
Published: December 2008

Abstract. Changes in calcium concentration were induced by an infusion of disodium-EDTA or calcium in 2 members of a family suffering from hypocalciuric hypercalcaemia (FHH) associated with interstitial lung disease. These changes in calcium demonstrated an inverse linear relationship with the changes in serum parathyroid hormone (PTH). Infusion of EDTA in control subjects and in patients with an adenoma or hyperplasia of the parathyroid glands also showed inverse relationships between calcium and PTH. The correlation between serum calcium and serum PTH was significant over the range observed during the induced hypo- and/or hypercalcaemia in controls and in patients with FHH or adenoma. The regressions were, however, shifted relative to each other: in comparison with controls, the FHH was displaced upwards and to the right, although not as far as the adenomas. These findings suggest the existence of an elevated set point for extracellular calcium (or calciostat) in FHH.
Release of cyclic AMP and progesterone from the isolated perfused luteal ovary of the PMSG treated rat
Authors: Sogn Jan , Abrahamsson Gun , Janson Per O.
Published: December 2008

Abstract. A model for in vitro perfusion of the isolated rat ovary was developed. In the luteinized ovaries of PMSG treated rats the relationship between perfusion flow and progesterone production was evaluated. A positive correlation was found indicating that a high blood flow rate may be necessary for an optimal secretion of progesterone from the fully developed corpus luteum in the rat.

Also the effects of a continuous exposure of LH on ovarian cyclic AMP and progesterone release was studied. A rapid and sustained increase in both cyclic AMP and progesterone release was seen and this release tended to have episodic pattern with elevations occurring at intervals between 30 and 90 min following LH.
Effects of oxytocin on cervical and uterine connective tissue
Authors: Wiqvist Ingrid , Norström Anders , Wiqvist Nils
Published: December 2008

Abstract. The effect of oxytocin on collagen metabolism in the cervix and lower uterine segment of pregnant women was studied by measuring the incorporation of [3H]proline in vitro. Oxytocin had a concentration related inhibitory effect on the labelling with [3H]proline. Addition of indomethacin did not influence the response to oxytocin indicating that the effect was not directly mediated by prostaglandins. Oestradiol-17β potentiated the effect of oxytocin. Vasopressin decreased the incorporation of [3H]proline slightly but the action of this hormone was significantly less than that of oxytocin. The results suggest that oxytocin under in vitro experimental conditions influences cervical connective tissue metabolism which is in contrast to current clinical experiences.
The effect of a luteinizing hormone releasing hormone (LRH) agonist (Wy-40,972), levonorgestrel, danazol and ovariectomy on experimental endometriosis in the rat
Authors: Jones Robert C.
Published: December 2008

Abstract. The effect of the LRH agonist, Wy-40,972, levonorgestrel or danazol on growth of endometrial explants in the intact female rat was studied. Sc injection of a single compound was begun 3 weeks after transplantation of a section of endometrium to the peritoneal wall. The animals were laparotomized to determine growth of the explant on day 1 of treatment. Injections were continued for 3 weeks at which time the animals were again laparotomized and the condition of the explant examined. Eight weeks after cessation of treatment the animals were sacrificed and the growth of the explant recorded. One or 30 μg of the LRH agonist produced a consistent inhibition of explant growth during treatment that was comparable to that obtained by ovariectomy. However, 8 weeks after cessation of injection, the majority of explaints exhibited renewed growth while all of the explants in the ovariectomized rats were only visually present. These result suggest that inhibiting or eliminating ovarian steroid production alone will not produce a permanent regression of the endometrial explant. Treatment with 30 μg danazol produced no effect and 1, 30 or 100 μg levonorgestrel produced none to limited inhibition of explant growth. However, 8 weeks after cessation of treatment explants in animals treated with either levonorgestrel or danazol were smaller in size than recorded prior to treatment. Thus, the inhibiting action of the peptide is rapid, whereas that of the steroids is, apparently, delayed. The observed activity of steroidal and non-steroidal compounds in this study demonstrates the usefulness of a rat model in the study of endometriosis.
Somatomedin A increments are diminished in acromegaly with concomitant hyperprolactinaemia
Authors: Hulting A.-L. , Hall K. , Werner S.
Published: December 2008

Abstract. The influence of prolactin (Prl) on growth hormone (GH) regulated somatomedin A (SMA) levels was studied in 30 patients with acromegaly before and after transsphenoidal pituitary surgery. Pre-operative GH levels were elevated in all patients and SMA levels in all but one patient. Eleven patients (33%) showed hyperprolactinaemia. There was no correlation between GH and SMA levels. Plasma GH did not differ in patients with GH and Prl producing adenomas compared to those with isolated GH hypersecretion. SMA levels, however, were significantly lower in patients with hyperprolactinaemia than in those with normal serum prolactin (P < 0.001).

After surgery GH decreased in all and SMA levels in all but one patient. Despite similar post-operative GH levels SMA decreased to significantly lower levels in patients with combined hypersecretion of GH and Prl compared to patients with normal prolactin levels (P < 0.05). Nine of the 11 patients with hyperprolactinaemia showed normal Prl after surgery.

The SMA levels in patients with acromegaly seem to be suppressed in patients with pre-operatively concomitant hyperprolactinaemia before as well as after adenomectomy regardless of the normalization of Prl. Our findings offer one explanation ot the lack of correlation between SMA and GH levels in acromegaly.
A new clonal strain of rat pituitary tumour cells: a model for non-regulated secretion of prolactin
Authors: Reymond Marianne J. , Nansel D. Dale , Burrows G. Howard , Neaves William B. , Porter John C.
Published: December 2008

Abstract. A new clonal strain of Prl-secreting cells derived from the transplantable rat pituitary tumour. 7315a, has been established in culture. The cells of this strain, designed 235-1, have a highly developed Golgi complex, an extensive rough endoplasmic reticulum, and a few small but no large dense-core granules. When inoculated into athymic mice and rats of the Buffalo strain, the 235-1 cells produce tumours, and the host animals have hypertrophied mammary glands that produce milk, indicating that Prl secreted by these cells has mammotrophic activity. In monolayer culture, the doubling time of 235-1 cells is 31 ± 1 h (mean ± se). The cells secrete Prl, a trace quantity of GH, but no LH, FSH, TSH, ACTH, or α-MSH. Prl is released at a rate of 257 ± 12 fg per h per cell. The cellular content of Prl is 424 ± 23 fg per cell. Prl secretion by 235-1 cells is not affected by dopaminergic agonists and antagonists, TRH, or oestradiol-17β but is inhibited in the presence of EGTA or monensin, an ionophore that is believed to act at the level of the Golgi complex. The subcellular distribution of Prl in 235-1 cells is different from that in rat pituitary cells. In 235-1 cells, Prl is associated not with a single set of dense particles as it is in pituitary cells but with 2 sets of subcellular particles, of which co-et co-sedimented with particles having lysosomal enzyme activity. These findings suggest that Prl secretion by 235-1 cells involves secretory pathways that are different from those seen in normal lactotrophs.
The differential diagnostic problems in unilateral euthyroid Graves' ophthalmopathy
Authors: Perrild Hans , Feldt-Rasmussen Ulla , Bech Karine , Ahlgren Preben , Hansen Jens Mølholm
Published: December 2008

Abstract. Nine consecutive patients with unilateral ophthalmopathy with suspected endocrine pathogenesis were investigated with a TRH test, a T3 suppression-test, thyroid autoantibodies and a subsequent computerized tomography (CT)-scan. All patients were clinically and biochemically euthyroid. Seven of 9 patients had a normal TRH test and 6 of 7 had a normal T3 suppression test. Slightly to moderately elevated microsomal and thyroglobulin (determined with radioimmunoassay) autoantibodies were found in 5 of 8 patients and in 1 patient thyroid stimulating immunoglobulins (TSI) were found. Three of the patients had normal thyroid function tests and no detectable thyroid autoantibodies. The subsequent CT-scan revealed that one of these had a maxillary tumour protruding into the orbita. The remaining 8 patients had enlargement of one (3 patients) or more (5 patients) eyemuscles. Two of the 8 patients had bilaterally enlarged eyemuscles, one of which was the patient with positive TSI. The remaining 6 patients had unilateral extraocular muscle enlargement. Thus, 2 of 9 patients had ophthalmopathy without thyroid dysfunction so-called isolated autoimmune ophthalmopathy or Graves' ophthalmopathy.

Thyroid function tests seem to be of limited value in the diagnosis between endocrine and non-endocrine eye disease, and we recommend the use of diagnostic imaging (e.g. CT-scan) in patients with unilateral exophthalmus in order to diagnose malignant processes.