bluuebunny/crossref_metadata_2025 huggingface dataset:
Improved sensitivity to adrenocorticotrophin after purification and pre-incubation of isolated rat adrenal cells
Authors: Goverde H. J. M. , Pesman G. J. , Benraad Th. J.
Published: December 2008

A highly sensitive bioassay for adrenocorticotrophin (ACTH) has been developed, in which isolated adrenal cells, purified previously by passage through a 5% BSA layer were pre-incubated for 1 h. The detection limit for hACTH1-39 in this system is 0.19 ± 0.10 (sd) fmol/ml. As a result of the purification step the ED50 for hACTH1-39 decreased from 14.1 ± 4.8 to 6.9 ± 1.2 fmol/ml. Pre-incubation of the purified cells decreased this value significantly to 4.0 ± 1.5 fmol/ml. For ACTH1-24 the increase of sensitivity after purification was even higher, the ED50 changing from 7.1 ± 4.2 to 1.6 ± 0.2 fmol/ml. After pre-incubation of the purified cells this value amounted to 0.8 ± 0.3 fmol/ml. After purification and pre-incubation of the adrenal cells the changes observed for the ED50's of hACTH1-32 and of a highly purified human hypophyseal extract paralleled exactly the change observed for hACTH1-39.

The improved sensitivity of the purified cell suspension might in fact represent a decrease in ACTH degradation. Both purification and pre-incubation could lead to removal or inactivation of enzymes which attach the polypeptide hormone. This hypothesis is supported by experiments in which the cell suspension has been contaminated with an adrenal homogenated prior to the purification and pre-incubation steps.

The present results indicate that pre-incubation of purified isolated adrenal cells has increased the sensitivity and that the amino acid sequence 33–39 is not involved in protecting the molecule from proteolytic attack.
Effects of immunizing rabbits against oestradiol-6-oxime-BSA on ovarian follicular development
Authors: Wielgosz G. J. , Low M. J. , YoungLai E. V.
Published: December 2008

Female rabbits were actively immunized either against bovine serum albumin (BSA) or oestradiol-6-oxime BSA. When the antibody titres were elevated they were sacrificed and various parameters measured. Uterine weights were significantly lower, and a large number of haemorrhagic and some cystic follicles were present in the ovaries of the oestradiol immunized group. Increased serum gonadotrophins, testosterone, oestradiol, and progesterone levels as well as greater serum binding of oestradiol were also noted. Examination of the response of isolated follicles to gonadotrophin treatment in vitro indicated that oestradiol immunization decreased the ability of isolated follicles to form androgen and oestrogen following gonadotrophin treatment; however, progesterone levels were high regardless of the presence or absence of gonadotrophins. These data suggest that oestradiol plays an important role in follicular development.
The effect of bromocriptine during early pregnancy in the rat: inhibition of implantation
Authors: Müller U. , Bauknecht Th. , Siebers J. W.
Published: December 2008

The increase in the number of the ovarian LH/hCG-receptors and of serum progesterone concentration during pregnancy in the rat is highly dependent on the presence of prolactin during the luteinization process. Blocking of the hypophyseal prolactin secretion by twice daily injections of 2 μg/g body weight bromocriptine into rats from the first day of pregnancy onwards prevents the increase in ovarian hCG-binding and progesterone production. Similar results are obtained by application of bromocriptine during the first three days only or either at day 1, 3 or 5 after mating. In all bromocriptine treated rats implantation of blastocysts does not occur. The failure to implant is not due to a teratogenic effect of bromocriptine onto preimplantation embryos, but is probably the consequence of changes of the uterine mucosa caused by the lack of progesterone production in the luteal cells.
Post-pubertal female psychosexual orientation in incomplete male pseudohermaphroditism type 2 (5α-reductase deficiency)
Authors: Cantú J. M. , Corona-Rivera E. , Díaz M. , Medina C. , Esquinca E. , Cortés-Gallegos V. , Vaca G. , Hernández A.
Published: December 2008

An 18 year-old 46,XY female-reared patient with incomplete male pseudohermaphroditism type 2 (5α-reductase deficiency) was studied. She had a male habitus, Wolffian ducts derivatives, normal testes and small phallus; there were no Mullerian duct derivatives nor gynaecomastia. Clinical and genetic data were typical of the diagnosis which was corroborated by endocrinological studies. Normal LH, FSH, testosterone (T) and oestradiol and decreased dihydrotestosterone (DHT) plasma levels before and after hCG administration were found; the T:DHT ratio was highly increased. The histopathological studies of a testis biopsy showed a normal adult male pattern, and the meiotic chromosomes were interpreted as normal. After assessment of her psychosexual orientation, successful surgical and medical therapy to maintain and improve her femaleness was effectuated. The post-pubertal gender role switch commonly observed in these female-reared patients is discussed.
Renal handling of 3,3',5'-triiodothyronine (reverse T3) compared to thyroxine and 3,5,3'-triiodothyronine in different thyroid function states in man
Authors: Rogowski Preben , Faber Jens , Siersbæk-Nielsen Kaj
Published: December 2008

The aim of the present work was to investigate the renal clearance of 3,3',5'-triiodothyronine (reverse T3, rT3) compared to thyroxine (T4) and 3,5,3'-triiodothyronine (T3) clearance. The urinary excretion of T4. T3 and rT3 was estimated by radioimmunoassay, serum unbound hormones (AFT4, AFT3, AFrT3) were measured using ultrafiltration technique. In 27 euthyroid controls the 24 h urinary T4 excretion was in median 1.7 nmol. T3 excretion 0.8 nmol and rT3 excretion 0.08 nmol. Serum AFT4 was in median 59 pmol/l, AFT3 7.9 pmol/l and AFrT3 2.2 pmol/l. Creatinine clearance was in median 93 ml/min. Median renal clearance of T4, T3 and rT3 were 26, 70 and 25 ml/min, and apparent tubular re-absorption was in average 77, 27 and 77%, respectively. In 18 hyperthyroid patients urinary hormone excretion was highly increased and was found parallel to the increase in serum concentrations of free hormones. Clearance and per cent tubular re-absorption of T4 and rT3 were equal to and not different from control values, but T3 clearance seemed to be increased to values higher than glomerular filtration rate (GFR). In 8 patients with hypothyroidism low urinary hormone excretion was found. Clearance of T4 and rT3 did not differ from control values, but T3 clearance was reduced.

Our data show that T4, T3 and rT3 are excreted by glomerular filtration of free hormones and suggest that tubular transport mechanisms are involved. The hypothesis is put forward that the renal handling of the thyronines is influenced by the number of the outer phenolic ring iodine atoms.
Diabetes in pregnancy: effects on the foetal and newborn rat with particular regard to body weight, serum insulin concentration and pancreatic contents of insulin, glucagon and somatostatin
Authors: Eriksson Ulf , Andersson Arne , Efendić Suad , Elde Robert , Hellerström Claes
Published: December 2008

Streptozotocin (SZ) treated virgin female rats, classified as either manifest diabetic (MD) or subdiabetic (SD) according to intraperitoneal glucose tolerance tests, were mated. Normal untreated rats (N) were also mated and used as controls. On gestational day 20 the MD foetuses showed decreased litter sizes, elevated blood glucose values and glucose-to-insulin ratios, decreased body and pancreatic weights and markedly diminished pancreatic insulin contents. The MD pregnancy was prolonged by two days and about 50 per cent of the offspring died perinatally. Both the wet and dry carcass weights of the non-viable MD offspring were increased, but when correction was made for the prolonged gestational period both the viable and non-viable newborns were lighter than those of the other groups. In the viable newborns of MD mothers the blood glucose concentration was elevated and the pancreatic contents of insulin and somatostatin decreased while that of glucagon remained unchanged. The 20-day-old SD foetuses showed increased pancreatic insulin and somatostatin contents but were identical to N foetuses in all other respects. Similarly, the newborns of SD mothers remained indistinguishable from those of the N mothers.

It is concluded that, in the rat, severe SZ-diabetes induced before pregnancy causes foetal growth retardation and decreased pancreatic insulin stores. The observations suggest that excessive hyperglycaemia in the foetus hampers the normal development of the pancreatic B-cell. The absence of macrosomia and hyperinsulinism in both the MD and SD newborns suggests a difference between human and rat foetal development in diabetic pregnancy.
Relationship between insulin secretion, insulin content and dry weight of single rat pancreatic islets
Authors: Wolters G. H. J. , Konijnendijk W.
Published: December 2008

Single islets were incubated at glucose 5 mm for 60 min and subsequently at glucose 15 mm for 30 min. The insulin content of the incubated islets was proportional to the dry weight of the islets. The insulin secretion (Y) demonstrated a curvilinear relationship with the dry weight (X) of the islets, which could be described by the function Y = aX⅔ (a being a constant). On basis of this function it can be calculated that the insulin secretion of a particular islet is proportional to its outer surface. The consequence of this is that small sized islets secrete relatively much more insulin than large islets. Islets isolated with either purified or crude collagenase gave the same results except that a higher basal insulin secretion was observed with crude collagenase.
Urinary tetrahydrocortisone and tetrahydrocortisol glucosiduronates in normal newborns, children and adults
Authors: Aranoff Gaya , Rosier Ariel
Published: December 2008

Utilizing a simple, highly specific radioimmunoassay (RIA), we measured the excretion of the glucosiduronate conjugates of tetrahydrocortisone (THE-gluc) and tetrahydrocortisol (THF-gluc) in adults (n = 16), children (n = 58) and newborns (n = 5), in order to establish a normal range of values for age and surface area. Both tetrahydrometabolites showed a linear inrease with age but became constant for all individuals except newborns when results were calculated per square meter. Newborns excreted disproportionately low levels of these metabolites for their size. In children of similar ages, when 24h urine collections (n = 13) were compared to spot AM specimens (AM-Sp) (n = 45) in which the daily volume was estimated by creatinine excretion, THE-gluc/m2 levels were significantly higher in AM-Sp urines but THF-gluc/m2 levels were similar. Levels of both metabolites were markedly elevated in two patients with hyperadrenal states and low in three patients with hypoadrenal states compared to normal values per m2. These results indicate that the RIA for THE-gluc and THF-gluc can be a useful indirect test of cortisol secretion in children as well as in adults. Although 24h urine collections are more accurate, creatinine corrected AM-Sp urines may be clinically useful when values of these metabolites per m2 are compared to appropriate controls.
Direct effects of medroxyprogesterone acetate (MPA) and megestrol acetate (MGA) on rat testicular steroidogenesis
Authors: Barbieri Robert L. , Ryan Kenneth J.
Published: December 2008

The effects of MPA and MGA on rat testicular steroidogenesis were examined by studying: 1) serum testosterone in hCG primed animals treated with MPA or MGA, 2) testosterone synthesis in rat Leydig cells cultured with MPA or MGA, 3) MPA and MGA binding to rat testis microsomal cytochrome P-450 and 4) MPA and MGA inhibition of enzymes of rat testicular steroidogenesis. In immature rats receiving 1.0 IU of hCG per day 20 mg/kg of MPA or MGA reduced serum testosterone by 57 and 56%, respectively. In mature male rats receiving 50.0 IU of hCG per day 20 mg/kg of MPA or MGA reduced serum testosterone by 40 and 29%, respectively. In rat interstitial cells cultured with 10 ng of rat LH, 1 μm MPA or MGA inhibited testosterone production by 32 and 23%, respectively. Addition of MPA or MGA to microsomal preparations resulted in a type I cytochrome P-450 difference spectrum. MPA and MGA inhibited rat testicular 17α-hydroxylase, 17,20-lyase, and the 3β- and 17β-hydroxysteroid dehydrogenases. These findings suggest that MPA and MGA inhibit rat testicular steroidogenesis in vivo and in vitro.
Effect of cyproterone acetate on platelet aggregability, fibrinolytic activity and fibrinolytic capacity in normal men
Authors: Føgh Marie , Knudsen Jens Bjerrre , Gormsen Johannes
Published: December 2008

Nine healthy men were treated with a daily dose of 5 or 10 mg of the anti-androgen cyproterone acetate. Patelet aggregability was increased in 6 of 9 men; fibrinolytic activity decreased in 7 of 7 and the fibrinolytic capacity decreased in 5 of 7 volunteers. We conclude that platelet aggregability, fibrinolytic activity and capacity may be modified by anti-androgen treatment and therefore attention should be paid to the coagulation parameters when cyproterone acetate is used.
Urinary 3',5'-cyclic adenosine monophosphate in relation to serum and urinary calcium in acromegaly and primary hyperparathyroidism
Authors: Halse Johan
Published: December 2008

A comparison of the interrelations between serum and urinary calcium values and the urinary excretion of cAMP in acromegaly (No. of subjects: 26), patients with primary hyperparathyroidism (n = 18) and control subjects (n = 42) is presented.

The cAMP excretion was greatest in primary hyperparathyroidism, but acromegalics also exhibited higher values for this parameter than controls. A positive correlation was found between serum calcium values and cAMP in primary hyperparathyroidism, while acromegalics showed no correlation between these parameters. In controls there was a negative correlation between serum calcium and cAMP. Serum calcium levels corrected for variations in total protein concentrations were elevated both in acromegaly and primary hyperparathyroidism, mostly in the latter.

Acromegalics and patients with primary hyperparathyroidism exhibited an increase in 24 h calcium excretion. While there was a negative relationship between urinary calcium excretion and cAMP in acromegaly, a positive correlation between these parameters was found in primary hyperparathyroidism. Controls showed a negative correlation between urinary calcium values and cAMP.

It is concluded that the role of the parathyroids in the regulation of calcium metabolism in acromegaly is different from that of both normal controls and primary hyperparathyroidism. It is postulated that an active form of Vitamin D plays a major role in the regulation of calcium metabolism in acromegaly.
Growth hormone dependent human serum stimulation of thymidine and sulphate incorporation into embryonic chicken cartilage
Authors: Jennings John , Buchanan Fred , Levitsky Lynne , Garland John T.
Published: December 2008

The embryonic chicken cartilage somatomedin bioassay was modified so that human serum stimulation of simultaneous [3H]methylthymidine and H2[35S]04 incorporation could be assessed. The assay consisted of a 6 h pre-incubation of 10 day pelvic rudiments in enriched buffer, followed by a 24 h incubation with buffer and low (0.5, 2 and 5% v/v) serum concentrations. Both labels were present for the final 6 h. Other modifications were shortening of washing, elimination of drying and weighing, and simplification of digestion.

Normal human serum produced a linear log dose-response with these serum concentrations. Potency ratios in patients with GH deficiency were less than those of normal adults for both thymidine 0.39 ± 0.05 (mean ± sem, n = 16, range 0.22-0.71) vs. 0.90 ± 0.05 (n = 19, 0.62—1.36, P< 0.001) and for sulphate 0.40 ± 0.04 (0.15—0.65) vs. 94 ± 0.05 (0.61—1.29, P< 0.001). Potency ratios for both labels rose following administration of a single dose (0.2 IU/kg im) of hGH to 4 GH deficient children.

The reliability of prediction of GH deficiency, reproducibility, and precision were similar to other Sm bioassays. The major advantages of these modifications were the ability to examine 2 cartilage metabolic processes simultaneously and the small amount of serum (350 μl) necessary for patient assays.
Hypothalamic-pituitary-testicular function in rats after supraphysiological doses of a highly active LRH analogue (buserelin)
Authors: Sandow J. , Rechenberg W. v. , Jerzabek G. , Engelbart K. , Kuhl H. , Fraser H.
Published: December 2008

Male pre-pubertal rats (60 g) were treated with the LRH analogue, [D-Ser(But)6]LRH(1—9)-nonapeptide-ethylamide (buserelin, Hoe 766), during 4 weeks by daily sc injections of 5, 50 or 500 ng peptide (group I, II and III). At the end of treatment, hypothalamic LRH content and arylamidase activity (LRH degrading enzyme) were not changed. Pituitary arylamidase activity was reduced, but the pituitary LRH receptors (tested by analogue binding in vitro) were not diminished. Pituitary accumulation of [125I]buserelin 60 min after iv injection was not modified and organ distribution in liver and kidney was unchanged. Pituitary responsiveness to the analogue was reduced at the highest dose, but there was significant LH-release at all three dose levels. Testosterone production in vitro (stimulated by hCG) was unaltered in group I and dramatically reduced in group II and III. Testicular testosterone content and hCG binding by testes homogenates were dose-dependently reduced. Histology of the testes after 4 weeks treatment showed minimal impairment of spermatogenesis at the highest dose, whereas the epididymis was almost devoid of sperm. The results indicate, that low dose treatment with a highly active LRH analogue, buserelin, does not interfere with pituitary responsiveness (LRH receptors and LH-release) and testicular function (testosterone production, testosterone content, LH-receptor level). At higher doses, pituitary and testicular responsiveness are dose-dependently inhibited. At the pituitary level, LRH receptors were not reduced. The antifertility effect of supraphysiological doses at the testicular level is explained by an LH-dependent loss of LH-receptors.
24-h profile of serum rT3 and serum 3,3'-T2 in normal man
Authors: Weeke Jørgen , Laurberg Peter
Published: December 2008

In a previous study we found a night surge in serum free T3 varying in parallel with that of serum TSH. In order to evaluate whether diurnal alterations in peripheral iodothyronine monodeiodination may be involved we have measured two products of peripheral deiodination, 3,3',5'-T3 (rT3) and 3,3'-T2 in serum samples obtained at short intervals during a 24-h period in 5 normal male subjects. Serum rT3 was rather stable during the period albeit with a trend towards lower levels during the night when the subjects were in bed. In order to obtain a measure of free rT3 a free rT3 index was calculated using the combined variations in per cent free T4 and free T3. Night and day levels of this rT3 index were found identical, suggesting a lack of diurnal variation in serum free rT3. Likewise serum 3,3'-T2 levels were identical during the day and night periods.

The results suggest that variations in peripheral iodothyronine deiodinations are not involved in the night increase in serum free T3.
Immunochemical demonstration of human chorionic gonadotrophin (hCG) in tissue of breast carcinoma
Authors: Castro A. , Buschbaum P. , Nadji M. , Voigt W. , Tabei S. , Morales A.
Published: December 2008

Immunoreactive human chorionic gonadotrophin (hCG) was found in 9 of 65 surgically removed malignant breast tumours. The concentrations found ranged from 5 to greater than 500 mIU hCG/g tumour. Of the nine, seven extracts were assayed for total protein content; when expressed as mIU/mg extract protein, the hCG concentrations ranged from 0.28 – > 18.2 mIU/mg protein. Comparison of oestrogen receptor and hCG presence in the tumours showed no strong correlation. All tumours in which hCG was detected were shown to be of ductal origin.

The hCG was measured by a β-chain specific radioimmunoassay which measures only hCG even in the presence of high levels of other gonadotrophin hormones. In further study of these specimens an immunoperoxidase staining technique was used to stain for hCG in formalin-fixed sections of the same tumours assayed by RIA. This technique confirmed hCG in the positive specimens examined (tissue was available for 7 of the 9 positives) and no significant staining in any negatives. The hCG was shown to be localized within the cytoplasm and on the surface of the malignant cells but not in surrounding normal cells. This intracellular localization demonstrates that the malignant cells may produce hCG, rather than stimulating the pituitary to do so.
Familial Cushing's syndrome with primary adrenocortical microadenomatosis (primary adrenocortical nodular dysplasia)
Authors: Schweizer-Cagianut M. , Froesch E. R. , Hedinger Chr.
Published: December 2008

Cushing's syndrome was found in 2 of 4 siblings all of which also had other malformations. After bilateral adrenalectomy no hyperpigmentation was noted. Morphologically the adrenals of both siblings with Cushing's syndrome showed the typical lesions of the so-called microadenomatosis or primary adrenocortical nodular dysplasia with foci of eosinophilic giant cells. This is a new form of Cushing's syndrome due to an inborn error of the adrenals and no hypothalamicpituitary dysfunction.
Circadian rhythms in plasma levels of cortisol, dehydroepiandrosterone, Δ4-androstenedione, testosterone and dihydrotestosterone of healthy young men
Authors: Guignard Michel M. , Pesquies Pierre C. , Serrurier Bernard D. , Merino Danielle B. , Reinberg Alain E.
Published: December 2008

Three healthy males (18, 22 and 30 years of age; 85 kg/177 cm, 82 kg/181 cm and 75 kg/168 cm, respectively), synchronized with a diurnal activity (06.00 to 23.00 h) and nocturnal rest, volunteered for this study. Blood was sampled (venous catheter) hourly during a 24 h span. A radiocompetition method was used for cortisol determinations. Other steroids were first extracted (ethyl-ether) from each plasma sample, then chromatographed on a celite column to isolate 3 fractions: 1) Δ4-androstenedione (Δ-4); 2) dihydrotestosterone (DHT) and dehydroepiandrosteone (DHA); 3) testosterone (T). A radioimmunological assay was used thereafter for the determination of androgenic steroids. Statistically significant (both conventional and cosinor methods) circadian rhythms were detected (P < 0.005). Acrophases (peak times) occurred in the following order: cortisol (07.28), DHA (08.43), Δ-4 (09.54), T (11.15) and DHT (16.37). The respective circadian amplitudes of DHA and Δ-4 were smaller than those of cortisol while the amplitudes T and DHT did not show differences statistically significant from each other.
Effects of pentobarbital on hypothalamic catecholamines and LRH activities
Authors: Kalra S. P. , Simpkins J. W. , Kalra P. S.
Published: December 2008

Pentobarbital (Pnt) injection at 12.30 h to ovariectomized rats suppressed the LRH contents of the medial basal hypothalamus (MBH) in association with a significant fall in serum LH 60–90 min later. The LRH contents in the preoptic area (POA) were unchanged in Pnt treated rats. A similar effect on LRH levels in the MBH was also evident in ovariectomized rats pre-treated with oestradiol benzoate. Pnt administration rapidly reduced the noradrenergic (NE) turnover in the MBH and POA, whereas dopamine (DA) turnover was unaltered. These studies show that: (i) the apparent decrease in LRH secretion (release + contents) following Pnt treatment was associated with a fall in the hypothalamic NE neurotransmission, and (ii) LRH neurons and fibres in the MBH alone respond to Pnt treatment.
Corticotrophin, growth hormone and prolactin deficiencies with hypoaldosteronism and corticosteroid-reversible hypothyroidism in Sheehan's syndrome. Clinical and anatomical correlations
Authors: Jordan Richard M. , Cook David M. , McDonald Walter J. , Houghton Donald C. , Kendall John W.
Published: December 2008

Deficiencies of corticotrophin (ACTH), growth hormone, and prolactin were documented in a woman with diabetes mellitus and Sheehan's syndrome. The patient's ACTH deficit appeared to be secondary to a hypothalamic abnormality since on two occasions the patient had a marked plasma ACTH response to vasopressin but not to insulin induced hypoglycaemia. It is postulated that the deficits of these three adenohypophysial hormones were instrumental in causing a severely impaired aldosterone secretory capacity in response to sodium restriction and an angiotensin infusion. In addition, the patient had an unusual form of thyroid dysfunction that was in part reversed with hydrocortisone replacement. The patient's unfortunate death during a hypoglycaemic crisis allowed correlation between her extensive antemortum endocrine testing and her pathologic anatomy.
Adrenocortical function in idiopathic haemochromatosis
Authors: Charbonnel B. , Chupin M. , Lucas B. , Chupin F. , Guillon J.
Published: December 2008

In idiopathic haemochromatosis, excessive iron deposits include adrenal cortex, and mainly the zona glomerulosa. In this view, we measured basal and poststimulative values of plasma cortisol, aldosterone and renin activity (RA) in two groups of patients: 1) 9 normal-salt repleted subjects (NSR) who were subjected to iv ACTH and furosemide tests, 2) 10 patients who were subjected to chronic salt depletion (CSD), to iv ACTH and furosemide tests. The results were compared with two groups of 7 healthy volunteers (NSR and CSD). In the patients, basal cortisol values were either normal or increased in cases of poorly controlled diabetes (21 ± 2.1 μg/100 ml, P < 0.01) and cortisol increase after ACTH injection was normal (to 43.3 ± 4.3 μg/100ml). In the 9 NSR patients, basal aldosterone (7.75 ± 1.5 ng/100 ml) and RA (1.55 ± 0.27 ng/ml/h) values were normal; aldosterone and RA rose after furosemide injection: these increases were similar in these patients (respectively to: 13.5 ± 2.2 ng/100 ml and 4.3 ± 0.6 ng/ml/h) and in the 7 NSR controls. In the 10 CSD patients, basal aldosterone and RA values were always increased (26.5 ± 3.2 ng/100 ml and 8.5 ± 2.3 ng/ml/h) as much as in the 7 CSD controls. After ACTH administration, aldosterone values (26.1 ± 4 in NSR patients, 54 ± 8 ng/100 ml in CSD patients) were the same as in the two control groups. This study suggests that there is no adrenocortical deficiency in idiopathic haemochromatosis, in spite of excessive iron deposits in the adrenal cortex.
No inhibition of corticotrophin (ACTH)-hypersecretion in adrenal insufficiency by somatostatin
Authors: Jara-Albarrán A. , Bayort J. , Caballero A. , Eusebio R. , García-Peris P. , Toledano E. , Pérez-Modrego S.
Published: December 2008

Somatostatin (250 μg as a bolus iv and 250 μg as a I h infusion) was administered to 6 patients with primary adrenal insufficiency (Addison's disease).

The fall in plasma ACTH during the infusion period ranged between 0–30% with a mean reduction of 11.2 ± 11.6%.

These findings suggest that with the method employed, somatostatin is not an inhibitor of ACTH secretion in a condition in which glucocorticoids are lacking.
Inhibition of LH-stimulated cyclic AMP formation in pre-ovulatory rat granulosa cells by follicular fluid
Authors: Nordenström Knut , Sjögren Anita , Hamberger Lars
Published: December 2008

Immature female rats were injected sc with a single dose of PMSG to induce growth and maturation of ovarian follicles. In the morning of prooestrus the rats were given a single ip injection of LH (10 μg/rat) or 0.154 m NaCl, 2 h prior to sacrifice. Granulosa cells were isolated from the pre-ovulatory follicles and incubated in Krebs bicarbonate buffer, for 1 h with or without in vitro addition of various test substances. Following incubation the amounts of cAMP in tissue plus medium were determined.

It was found that the isolated granulosa cells exposed to LH in vivo responded to the addition of LH in vitro with a production of high amounts of cAMP, i.e. these cells were not refractory to LH stimulation and in fact responded better than granulosa cells isolated from ovaries not exposed to LH in vivo. The addition to the incubation medium of follicular fluid (FFl) obtained from pre-ovulatory follicles decreased the effect of LH in vitro when added at a final concentration of 1% and completely abolished it at a concentration of 3%. Removal of steroids from the FFl did not influence the inhibitory effect and the addition of a phosphodiesterase inhibitor (IBMX) in vitro did not alter the results in principle.

These results point to the existence of a factor in the FF1 which interacts with the sensitivity of the isolated preovulatory granulosa cells to repeated exposures to LH. Characterization of this factor is subject to further investigations.
Reduced glucose incorporation to triglycerides following chronic exposure of human fat cells to growth hormone
Authors: Nyberg Gudrun , Boström Stig , Johansson Rolf , Smith Ulf
Published: December 2008

Using the tissue culture technique we have recently demonstrated that long-term exposure of human adipose tissue to human growth hormone (GH) in vitro leads to an impairment in glucose incorporation into triglycerides. This effect was further studied in the present investigation. Biopsies of human adipose tissue which had been cultured for one week with or without GH were studied in subsequent short-term incubations where the conversion of glucose to CO2 and to total lipids was determined. The formation of CO2 was not changed by previous exposure of the biopsies to GH whereas the incorporation of glucose into triglycerides was reduced by about one third. Total glucose metabolism, as determined from the sum of the two pathways, was significantly reduced.

The activities of three glycolytic enzymes were determined in biopsies of human adipose tissue which had been cultured with or without GH for one week. The activity of phosphofructokinase was reduced, while the hexokinase and the glucose-6-phosphate dehydrogenase activities were unchanged.

The diminished activity of phosphofructokinase, the enzyme considered to be rate-limiting for glycolysis in human fat cells, may be responsible for the decreased rate of glucose metabolism found.
Isolation of the insulin binding alpha-one serum globulin by gelfiltration and immunosorption1
Authors: Gjedde Flemming , Gjedde Bodil
Published: December 2008

A radioactive alpha-one globulin, formed after infusion of labelled insulin into cats, was purified by gelfiltration and by immunosorption on immobilized antibodies against insulin. Judged by crossed immunoelectrophoresis the protein appeared to be pure. Only a fraction, about 17 per cent, of the radioactive globulin was retained by the immunosorption column. However, antibodies raised in rabbits against this protein could precipitate nearly all of the alpha-one globulin.
Clinical trial with levo-norgestrel and testosterone oenanthate for male fertility control
Authors: Føgh Marie , Corker Charles S. , McLean Helen , Hunter William M. , Petersen Ivan Bruunshuus , Philip John , Schou Geert , Skakkebæk Niels E.
Published: December 2008

Two groups of six men took levo-norgestrel (250 or 500 μg daily) by mouth and testosterone oenanthate (200 mg monthly, intramuscurlarly) for six months. A three months placebo period preceded the medication which was followed by a recovery phase of 6–10 months. Two volunteers withdrew due to side effects. The five men taking the low doses of levo-norgestrel (250 μg) exhibited a reduction in sperm count, but not to azoospermia. The high dose of levo-norgestrel (500 μg) was more effective, sperm count was reduced to < 6 × 106/ ml in 3 of 5 volunteers and to < 17 × 106/ml in the remainder. s-Testosterone, LH and FSH were decreased by the treatment. The men had no toxicological side effects or changes in libido and potency. During the recovery period sperm counts, sperm morphology, s-testosterone, LH and FSH returned to normal levels.
Testosterone metabolism in human bone
Authors: Schweikert H. U. , Rulf W. , Niederle N. , Schäfer H. E. , Keck E. , Krück F.
Published: December 2008

The conversion of [1,2,6,7-3H]testosterone2 to [3H]dihydrotestosterone has been assessed in ground spongiosa of normal and osteoporotic bone. The tissue was obtained from 23 patients, 18 women, 3 men and 2 children who were undergoing orthopedic surgery.

The formation of dihydrotestosterone was demonstrated in all samples examined. The half maximum rate of dihydrotestosterone formation occurred at a substrate concentration of 0.3 μm a value similar to that reported for dihydrotestosterone formation in other androgen target organs.

Under the standardized conditions utilized in this study the rate of dihydrotestosterone formation did not differ significantly in normal as compared to osteoporotic bone. Furthermore, the conversion of testosterone to androstenedione was also similar in osteoporotic and normal bone.

Based on these studies it seems reasonable to conclude that dihydrotestosterone rather than testosterone is the active intracellular androgen in human bone since in other androgen target tissues androgen action is mediated by dihydrotestosterone if 5α-reductase is present.
The role of oestrogens on gonadotrophin secretion in the testicular feminization syndrome1
Authors: Medina Martha , Ulloa-Aguirre Alfredo , Fernández Maria A. , Pérez-palacios Gregorio
Published: December 2008

The role of oestrogens on gonadotrophin secretion was assessed in three related patients with the complete form of testicular feminization syndrome. Serum LH and FSH levels were measured before and after I.RH stimulation as well as before, during and after chronic clomiphene citrate administration. Moderately elevated LH basal levels with a significant LH rise following I.RH were observed. Normal or even low FSH level with poor response to LRH were found in all subjects.

Administration of clomiphene citrate resulted in a significant serum LH increase without any change of FSH. Following castration both LH and FSH rose and a normal response to LRH was observed.

These results were interpreted as demonstrating that, while endogenous oestrogens modulate LH secretion in patients with androgen unresponsiveness, it plays no role in regulating FSH secretion and suggested that a factor of testicular origin without androgenic or oestrogenic activity is responsible for FSH regulation.
Cyclic AMP release from normal human thyroid slices in response to thyrotrophin
Authors: Bidey Stephen P. , Marshall Nicholas J. , Ekins Roger P.
Published: December 2008

Slice preparations of normal human thyroid tissue were incubated in vitro with TSH. The cyclic AMP contents of slices were determined at intervals up to 120 min, and cyclic AMP in the incubation medium was also estimated for each incubation period. Slice cyclic AMP levels were related both to incubation time and TSH dose. In response to 10 mU TSH/ml, slice cyclic AMP levels were maximal within 60 min, and were not significantly changed at 120 min. Cyclic AMP was detectable in the medium within 10 min of slice exposure to TSH, and increased throughout the initial 60 min of incubation. Cyclic AMP release during this period was dependent on both TSH dose and incubation time. Between 60–120 min, however, cyclic AMP release partially lost its TSH dose-dependency, and 0.5–5.0 mU TSH/ml were equipotent with respect to the final medium cyclic AMP level attained. Slices incubated without TSH released only small amounts of cyclic AMP, and maximal levels were attained within 20 min. In contrast to the adenylate cyclase response of thyroid membrane preparations, which was stimulated by NaF, suggesting that cyclic AMP release was not a result of the stimulation of damaged cells.

These findings demonstrate the importance of cyclic AMP release from human thyroid slices, following in vitro exposure to TSH, and suggest that, after incubation periods such as are used for the functional biodetection of thyroid stimulators, the magnitude of cyclic AMP release may be of quantitative significance.
The relation between gastrin, gastric acid and thyroid function disorders
Authors: Wiersinga W. M. , Touber J. L.
Published: December 2008

Hvpergastrinaemia was found in 11 out of 24 untreated hyperthyroid patients (Graves' disease or nodular goitre). Seven patients had a co-existent (autoimmune) atrophic gastritis. In the remaining 17 patients plasma T3 was positively related to plasma gastrin, and negatively to gastric acid output; there was no relation between gastrin levels and acid output. Acid instillation into the stomach revealed a normal negative feedback of acid upon gastrin release.

Sixteen hyperthyroid patients were restudied when euthyroid. Plasma gastrin decreased from 171 (51–1188) ng/l before treatment to 69 (39–392 ng/l after treatment (P < 0.002), and maximal acid output increased from 1.55 (0.00–22.75) to 8.03 (0.00–26.60) mmol H+/h (P < 0.01) (median values; range in brackets). However, in 4 patients with complete achlorhydria before and after treatment plasma gastrin decreased to the same extent as in the patients with gastric acid secretion.

We conclude that thyrotoxic hypergastrinaemia cannot be fully explained by the low gastric acid output in hyperthyroidism.
Uptake of L-triiodothyronine into human cultured lymphocytes
Authors: Holm Ann-Charlotte , Wong K. Y. , Pliam Nathan B. , Jorgensen Eugene C. , Goldfine Ira D.
Published: December 2008

The cellular uptake of [125I]L-triiodothyronine and its analogues was investigated in IM-9 human cultured lymphocytes. Uptake of L-triiodothyronine was one half maximal within 15 min of incubation and maximal within 45 min. The efflux of the hormone followed first order kinetics having a one half time of 15 min. Treating the cells with either the mitochondrial inhibitors antimycin-A and potassium cyanide, or lowering the incubation temperature to 12°C, markedly reduced uptake.

The uptake of [125I]L-triiodothyronine was saturable having an affinity constant (Kd) of 110 nm. When thyroid hormone analogues were studied D-triiodothyronine and triiodothyroacetic acid (analogues known to bind avidly to nuclear receptors) competed only weakly with [125I]L-triiodothyronine for uptake. These findings indicated the importance of the intact L-alanine side chain of the thyroid hormone molecule for its uptake into lymphocytes. Other studies, with cultured rat hepatocytes, demonstrated a similar saturable uptake system for [125I]L-triiodothyronine. These studies suggest, therefore, that the uptake of thyroid hormones and their analogues into cells may be an important step in the biological actions of these hormones.
Stimulation of residual insulin secretion by glibenclamide in insulin dependent diabetics
Authors: Burke B. J. , Sherriff R. J.
Published: December 2008

Residual insulin secretion, reflected by the presence of C-peptide in serum and urine, has been demonstrated in 5 of 10 insulin-requiring diabetics of less than 10 years' duration tested. The C-peptide response, in the C-peptide secretors, showed a significant increase in both serum and urine after 4 weeks' treatment with 15 mg glibenclamide daily in addition to their usual insulin regime although no beneficial effects in metabolic control were detected. It is suggested that glibenclamide might be a useful adjunct to insulin therapy in insulinrequiring diabetics who still secrete C-peptide.
Study of the role of adrenocortical cyclic AMP and cyclic GMP on ascorbic acid depletion and corticosteroidogenesis by analysis of circadian rhythms
Authors: Guillemant Josette , Reinberg Alain , Guillemant Serge
Published: December 2008

cAMP, cGMP and ascorbic acid were each measured in the adrenal cortex of young adult male rats killed in groups of 8 animals at around 08.00, 12.00, 18.00, 20.00, 00.00 and 04.00. The animals had been synchronized with natural daylight (07.00–19.00) and darkness alternation for 2 weeks. Plasma corticosteroids were determined in blood samples collected at the time of killing. The results were analyzed by both conventional and cosinor statistical methods. The existence of circadian rhythms was confirmed with P < 0.005 for the four variables studied. The extreme values ranged between 65 ± 4.3 (sem) and 745 ± 101 nm for corticosterone, 9.06 ± 0.4 and 13.23 ± 0.92 pmol/mg protein for cAMP, 0.69 ± 0.05 and 1.6 ± 0.17 pmol/mg protein for cGMP and 147 ± 7 and 218 ± 16 nmol/mg protein for ascorbic acid. The estimated acrophases were located at ≅ 21.00 for plasma corticosterone, at ≅ 11.00 for adrenocortical ascorbic acid (the corresponding nadir being located at ≅ 23.00), at ≅ 01.00 for cAMP and at ≅ 07.00 for cGMP. Expressing the data as the ratio of cAMP to cGMP reveals a circadian variation with a 21.00 peak synchronous with the corticosterone acrophase and just preceding the ascorbic acid nadir. A highly significant (P < 0.001) increase in corticosterone and a less significant (P < 0.05) decrease in ascorbic acid occurred until 16.00, whereas the cAMP levels remained low and constant. During the same period the cGMP levels decreased very significantly (P < 0.001). These phase relationships suggest that under physiological conditions, the action of corticotropin for both corticosteroidogenesis and ascorbic acid depletion might be mediated by the relative concentrations of cAMP and cGMP.
Effects of insulin treatment on the activities of phosphoprotein phosphatase and its inhibitors
Authors: Chang L. Y. , Huang L. C.
Published: December 2008

An increase in glycogen synthase phosphatase (phosphoprotein phosphatase) activity was observed in the rat skeletal muscle extract following insulin administration. The phosphoprotein phosphatase activity present in the muscle extract from insulin treated rats was observed to remain elevated after the extract had been subjected to a molecular sieve chromatography. These results indicate that the stimulatory effets of insulin is due to modification of phosphatase itself or some macromolecular weight modifiers.

The heat-stable protein inhibitors of the phosphoprotein phosphatase were isolated from skeletal muscle of insulin treated and control rats and their inhibitory potencies were compared over a wide range of protein concentrations. The inhibitory potency in the insulin treated rat skeletal muscle was found to be significantly less than that in the control muscle. Since type-1 inhibitor is well-known to be active only after being phosphorylated by cyclic AMP-dependent protein kinase, we suggest that the observed change in phosphoprotein phosphatase inhibitor potency is most likely mediated by an alteration in the phosphorylation state of type-1 inhibitor.
In vivo sequential model for thyroglobulin iodination
Authors: Miquelis R. , Simon C.
Published: December 2008

In order to study sequential events at the follicular level, thyroglobulin (Tg) iodination kinetics were followed by double labelling experiments. The experiments were performed on two groups of rats receiving 50 μg (group 50) and 5 μg (group 5) of iodine daily. The rats were isotopically equilibrated with 125I. Each subgroup received a single dose of 131I at various periods of time between 2 and 48 h. The renewal kinetic curves, displayed by the iodine specific radioactivity (SRA = 0/00 of injected dose, μg 127I) show that, in both groups, Tg SRA presents two maxima, the first at about 6 h, the second at about 48 h, when, as shown for group 50, the SRA of the precursor iodide decreases monotically. This is interpreted as the result of two iodination steps: 1) a direct iodination of newly exocytosed Tg molecules, 2) a delayed iodination on Tg molecules previously stored within the colloid. The Tg SRA ratio between the two maxima indicates that the renewal assured by the delayed iodination is 2.5 times greater than that assured by direct iodination in group 50, while resting equal in group 5. For both groups, the hormonal renewal, in comparison to the iodotyrosine renewal, increases during the direct iodination, but stays constant after the delayed maximum value is reached: it is concluded that the higher hormogenesis efficiency could only be reached after the delayed iodination, probably because of higher iodine content of Tg molecules. These results emphasize the importance of the role of the Tg molecules stored in the colloid in the process of iodide organification and indicate that iodination, for the greater part, does not take place on de novo synthesized Tg molecules.
Comparison of intraperitoneal, intraportal and intravenous insulin infusion
Authors: Poulsen J. S. Dirch , Smith Mogens , Deckert Marja , Deckert Torsten
Published: December 2008

In order to avoid complications induced by long-term infusions of insulin into the portal vein, we examined the effect of intraperitoneal (ip) insulin infusion on arterial plasma insulin and glucose concentrations in 6 pigs, made diabetic by a constant intravenous (iv) infusion of glucose, epinephrine and propranolol.

Insulin was infused by an electromechanical programmable mini-pump (Pharmaject Micro Infusion System®, Pharmacia Electronics) as a booster injection of 46 mU highly purified porcine insulin Leo®/kg body weight, followed by 3 infusion periods of 30 min each with stepwise decreasing infusion rates of 1.6–0.8 and 0.2 mU/kg/min in a total volume of 192 μ1. Insulin was infused in a peripheral vein, a portal vein and into the peritoneal cavity.

A steep rise of arterial plasma insulin was demonstrated followed by a slow and identical decline in the peripheral and portal experiments, whereas only a small increase of plasma insulin was seen in the ip experiment, indicating insufficient absorption of insulin from the peritoneal cavity. The decrease of plasma glucose was identical in the peripheral and portal vein experiments, indicating that insulin infused in the portal vein does not seem to have a higher hypoglycaemic effect, than insulin infused in a peripheral vein.

Intraperitoneal insulin infusion seems not to be a practical substitute for iv insulin infusion.
Corticotropin- and lysine-vasopressin induced changes of plasma corticosteroids and testosterone in the adult male pig
Authors: Hahmeier W. , Fenske M. , Pitzel L. , Holtz W. , König A.
Published: December 2008

Intravenous injection of 10.0 μg/kg body weight synthetic corticotropin (1-24 ACTH) into chronically cannulated boars resulted in significantly elevated plasma corticosteroid and testosterone levels between 20 and 140 min (corticosteroids) and 20–80 min (testosterone) after injection. Administration of lysine-vasopressin (LVP) at doses of 0.1, 0.2 and 0.4 IU/kg body weight elicited a significant increase of plasma corticosteroids between 20 and 40 min after injection; on the other hand, plasma testosterone concentrations tended to fall when compared to pre-treatment levels.

From our results it can be concluded that exogenously applied ACTH can effectively stimulate the release of corticosteroids and testosterone. Intravenous administration of LVP results in significantly, although not maximally increased plasma corticosteroid concentrations; the release of endogenous ACTH induced by LVP injection, on the other hand, appeared to be too small to stimulate testosterone release significantly.
Disturbances in sexual differentiation of rat foetuses following spironolactone treatment
Authors: Hecker A. , Hasan S. H. , Neumann F.
Published: December 2008

Pregnant rats were treated with 40 mg spironolactone (sp) po from the 13th to the 21st day p.c. The foetuses were prepared and histologically examined on day 22. The male foetuses showed distinct signs of feminization especially of the external genitalia. The anogenital distance was nearly 48% shorter than that of the controls. The prostatic utricle persisted more distinctly, and the number and size of the prostatic buds were significantly reduced. The degree of feminization of the male foetuses which is achieved under the influence of sp (40 mg/day) is the same as that which can be induced by 1–3 mg cyproterone acetate.