bluuebunny/crossref_metadata_2025 huggingface dataset:
SYMPATHECTOMY AND PROSTAGLANDIN DEFICIENCY DO NOT PREVENT GASTROGENIC HYPERGLYCAEMIA AND HYPERINSULINAEMIA
Authors: Schusdziarra V. , Rouiller D. , Unger R. H.
Published: December 2008

To examine the mechanism of the recently reported effect of an acidified intragastric test meal on insulin release and glucose homeostasis, a liver extract test meal at either pH 2 or pH 7 was instilled into the stomach of normal dogs and dogs with a chemical sympathectomy or indomethacin-induced prostaglandin deficiency, all of which had a bisected pylorus and gastric fistula. In the normal dogs the instillation of the liver meal at pH 2 elicited a significant rise in plasma glucose, glucagon and insulin levels, while in response to the meal at pH 7 only glucagon rose significantly. This was not altered in chemically sympathectomized dogs, nor during the infusion of indomethacin. In all experiments gastrin or gastric glucagon release in response to the meal at pH 2 was either lower than or similar to the response to the meal at pH 7. These data suggest that the influence of the stomach upon islet cell function and glucose homeostasis does not depend on either adrenergic innervation or the presence of prostaglandins, but rather is mediated by a yet undetermined mechanism.
THE MECHANISM OF THE ACID ACTIVATION OF RABBIT UTERINE RENIN
Authors: Jørgensen Jørgen
Published: December 2008

Besides active renin an inactive form of renin could be demonstrated in uterine tissue. On gel filtration it was eluted as a molecule of slightly higher molecular weight than active renin, and it could be irreversibly activated by acidification at 37°C. The activation had a pH optimum between pH 3.8 and pH 5.3. Acid activated uterine renin was found identical to active uterine renin by 1) the formation of angiotensin I with time after addition of rat substrate, 2) the pressor response in the rat, 3) neutralization by antirenin and 4) similar Michaelian constants. Repeated freezing and thawing, acidification at 4°C and dialysis against 4 mol/l NaCl did not give any activation. A lower rate of activation of diluted samples and activation by trypsin at pH 7.4 suggest that proteolytic enzymes are involved in the activation.
Dose and sex related effects of aromatic aminoacids decarboxylase inhibitors on serum prolactin in humans
Authors: Polleri Alessandro , Masturzo Paola , Murialdo Giovanni , Carolei Antonio
Published: December 2008

Single doses of carbidopa and benserazide, two inhibitors of aromatic aminoacids decarboxylase, have been given orally to healthy women and men aged 19 to 32 years. Serum prolactin levels increased in respect to baseline levels when 80, 125 or 250 mg of carbidopa and 10, 20, 30, 50, 80 or 125 mg of benserazide were given. The carbidopa doses of 20 and 50 mg were ineffective. Carbidopa induced the enhancement of serum prolactin at a later time and over a longer time span than benserazide. The effect on serum prolactin is dose dependent for both drugs. The hyperprolactinaemia obtained with 250 mg of carbidopa and with 125 mg of benserazide is significantly larger in women than in age matched men. The observed prolactin increase fits with the hypothesis that a diminution of the inhibitory effect of dopamine at the pituitary and/or at the median eminence levels may occur in connection to the pharmacologically impaired monoamine synthesis. An effect of serotonin cannot, however, be excluded.
The effect of hGH on hypothalamic-pituitary-thyroid function in patients with pituitary dwarfism
Authors: Demura Reiko , Yamaguchi Hajime , Wakabayashi Ichiji , Demura Hiroshi , Shizume Kazuo
Published: December 2008

The effect of growth hormone (hGH) on the hypothalamic-pituitary-thyroid function was studied in patients with pituitary dwarfism. Twenty-six patients were given KABI hGH, 0.5 U/kg/week, for a period of 4—18 months. Three groups of patients were identified according to their T4 levels before and during the treatment. Group 1: T4 levels were initially normal and stayed in the normal range throughout a course of treatment. Group 2: T4 levels were initially normal but dropped to the subnormal range after hGH. Group 3: T4 levels were initially subnormal and decreased further after hGH. Changes in T4 levels after hGH in groups 2 and 3 were accompanied by a decrease in plasma T3RSU without concomitant decrease in plasma T3. Clinically, most of them lacked symptoms and signs of hypothyroidism and exhibited a good growth response to hGH. Plasma TSH response to TRH in these patients revealed a sustained delayed pattern, which was suggestive of hypothalamic hypothyroidism. This pattern of TSH response to TRH became further exaggerated after hGH therapy. In contrast, TSH response to TRH among patients in group 1 was normal and was not influenced by hGH. Administration of 4.0 U of KABI hGH daily for 21 consecutive days to 3 patients resulted in a shortened half-life of T4 and inversely prolonged that of T3.

These results suggest that various degrees of TRH deficiency exist among patients with idiopathic pituitary dwarfism. Therapy with hGH discloses a mild TRH deficiency by accelerating the half-life of T4. This also causes a further drop in the T4 levels in those with marked TRH deficiency. The development of clinical hypothyroidism is not so obvious in these patients because of inverse delay in half-life of T3 by hGH.
Congenital goitre due to "thyroid peroxidase-iodinase defect"
Authors: Niepomniszcze Hugo , Coleoni Aldo H. , Targovnik Héctor M. , Iorcansky Sonia , Degrossi Osvaldo J.
Published: December 2008

A 16-year-old male cretin with congenital goitrous hypothyroidism and 95% discharge in the perchlorate test underwent thyroidectomy. Thyroid studies disclosed negligible peroxidase (TPO) activity in the tyrosine iodinase assay, 6 nmoles I− inc./g (normals: 220—410). Using the same particulate preparations, a high activity was obtained in the guaiacol assay, 485 U/mg vs. 176 U/mg of a control gland. Goitre TPO was solubilized by treating the thyroid pellets with deoxycholate, trypsin and acetone. Soluble goitre TPO was further purified on Sephadex G-200. By this procedure we obtained a single peak of enzyme activity for oxidizing guaiacol, although no activity was found for iodinating tyrosine. I2 formation, as measured by the triiodide assay, was only 28% of that expected for normal TPO when compared for guaiacol oxidation. It is concluded that this abnormal TPO was the cause of the congenital hypothyroidism of the patient. We suggest the term "thyroid peroxidase-iodinase defect" for defining this newly found inborn error.
Effects of propylthiouracil and methylmercaptoimidazole on thyroglobulin synthesis
Authors: Monaco F. , Santolamazza C. , De Ros I. , Andreoli A.
Published: December 2008

The effect of 6-propyl-2-thiouracil (PTU), and 1-methyl-2-mercaptoimidazole (MMI) on thyroglobulin (Tg) biosynthesis has been studied in vivo and in vitro. In vivo experiments were performed in rats treated for 20 days with PTU or MMI. analyzing soluble and particulate, cold and 125I-labelled, Tg. Thyroglobulin biosynthesis was also investigated by in vitro experiments, incubating thyroid tissue with labelled amino acid and carbohydrate in the presence of antithyroid compounds.

It has been found that in vivo antithyroid agents decrease the amount of soluble Tg and increase the proportion of particulate Tg. Tg from treated animals is poorly iodinated being mainly represented by its 12S subunit.

In vitro studies demonstrate that PTU and MMI inhibit Tg biosynthesis which is impaired in the polypeptide synthesis as wellas in carbohydrate chains addition.

Thus the inhibition of the hormonogenetic processes induced by antithyroid treatment leading to a depressed iodinating activity also appears to be related to a significant impairment of the production of the Tg molecule, the specific iodine acceptor.
Inhibition of allogeneic lymphocyte E-rosettes induced by sera from newly diagnosed type I diabetics
Authors: Pozzilli P. , Di Mario U. , Javicoli M. , Menzinger G. , Andreani D.
Published: December 2008

Sera from 64 juvenile onset insulin-dependent diabetics (Type I diabetics) and 30 normal subjects were tested for their ability to inhibit sheep red blood cell rosette formation (E-rosette) by normal allogeneic lymphocytes.

Inhibition of E-rosette formation by greater than 20% was found with 16 (66%) sera from newly diagnosed patients, 3 (16%) sera from patients with duration of disease between 2 and 12 months and with 4 (18%) sera from diabetics with duration of disease between 1 and 7 years. On the other hand, only 2 (6%) control sera showed inhibitory effect.

No relationship between E-rosette inhibition and islet-cell antibodies presence, anti-lymphocyte antibodies occurrence, anti-HLA activity, blood glucose levels, respectively, was found.

Investigation of the properties of this inhibitory factor suggests that it is different from other substances that reportedly inhibit E-rosette formation.
Different dynamics of insulin secretion in the perfused pancreas of mouse and rat
Authors: Berglund Ove
Published: December 2008

The dynamics of insulin release were studied in the perfused pancreas of rats and mice. Perfusion of the rat pancreas with 20 mm D-glucose resulted in the classical biphasic release of insulin with a rising second phase. However, in normal C57BL/KsJ-mice and noninbred mice, whether fed or starved, the second phase was nearly constant. The secretory dymanics of KsJ-mice were essentially the same, whether the glucose concentration was 30 or 20 mm, whether the medium contained 2.56 or 8 mm Ca2+, and whether or not the medium was supplemented with 5 mm pyruvate, 5 mm glutamate, and 5 mm fumarate. Insulin secretion in these mice was almost totally inhibited by omission of Ca2+, and was markedly enhanced by 3-isobutyl-1-methylxanthine. Insulin release during the constant phase was reversed by lowering the glucose concentration. A second rise of glucose from 3 to 20 mm produced a secretory pattern very similar to the first response. These studies indicate that the dynamics of insulin secretion are somewhat different in rats and mice. Since similar results were obtained with C57BL/KsJ-mice and non-inbred mice, the liability of KsJ-mice to develop β-cell failure when stressed by the mutated db gene is not related to the constancy of the second insulin secretory phase.
Serum somatomedin activity measured as sulphation factor in peripheral, hepatic and renal veins of mongrel dogs: basal levels
Authors: Schimpff Rose-Marie , Donnadieu Marcel , Duval Michel , Leduc Brigitte
Published: December 2008

Serum somatomedin (SM) activity measured as sulphation factor on chick embryo cartilage was determined in peripheral (PV), hepatic (HV) and renal (RV) veins or 36 mongrel dogs. Mean SM activity ± sem was 0.53 ± 0.03 U/ml in peripheral and hepatic veins, and 0.61 ± 0.04 U/ml in renal vein (P<0.005). When the gradient of SM activity in hepatic or renal vein to that in peripheral vein, [HV]-[PV] or [HV]-[PV], was plotted versus SM activity in peripheral blood [PV], a negative correlation was found in the case of hepatic but not of renal blood. These data indicate that the kidney may be a production site of SM activity, whereas the liver is differently implicated in the overall regulation of SM activity.
Somatomedin production by rat liver in organ culture
Authors: Binoux M. , Lassarre C. , Seurin D.
Published: December 2008

Inhibitors of cartilage sulphation have been found to be released by the rat liver in organ culture. They cause a decrease in [35S]sulphate uptake by embryonic chick cartilage and, when added to a constant amount of serum, counteract the somatomedin (SM) activity of the serum. Both of these effects are dose-dependent. Their antagonistic action, investigated in the presence of increasing concentrations of serum, appeared to resemble non-competitive inhibition which would suggest different sites of action for SM and inhibitors.

Incubation of the liver explants with cortisol (0.01—1 μg/ml) increased the sulphation-inhibiting activity of the culture medium and the effect was dose-dependent. Simultaneous addition of cycloheximide suppressed the inhibition.

Gel filtration of the culture medium on Sephadex G 75 showed that: a) at pH 7.9, inhibitors eluted in the same fractions as [125I]SM-A bound to its carrier (apparent molecular weight ∼45 000); b) at pH 2.4, inhibitors still eluted as large molecules, but SM activity appeared in the same fractions as the dissociated [125I]SM-A. The question arises whether the cartilage sulphation inhibitor might not be the same molecule as the SM-carrier protein released by the liver.
Gastrinoma and phaeochromocytoma: is there a mixed multiple endocrine adenoma syndrome?
Authors: Nathan David M. , Daniels Gilbert H. , Ridgway E. Chester
Published: December 2008

A 51 year old man was found to have a malignant gastrinoma. A phaeochromocytoma had been diagnosed and removed previously. The occurrence of these two rare tumours in a single patient suggests the possibility of a crossover between MEA I and MEA II. Reported cases of the "crossover syndrome" are reviewed and the status of this phenomenon as a syndrome is discussed.
Congenital adrenal hyperplasia due to 11 β-hydroxylase deficiency: final diagnosis in adult age in three patients
Authors: Glenthøj A. , Nielsen M. Damkjær , Starup J.
Published: December 2008

Three patients, one male and two females, in whom the diagnosis of congenital adrenal hyperplasia (CAH) was made in early childhood were studied. The two females were treated with cortisone acetate from the age of 2 and 4 years, respectively, and later they both proved to be fertile. The male patient was only treated sporadically with cortisone acetate until the age of 33 years. He also became fertile when a more consistent treatment with prednisolone was started. The two female patients had a slight hypertension in childhood before the treatment was initiated but became normotensive on treatment. The male patient revealed a blood pressure of 180/130 mmHg at the age of 33 years. In this patient the treatment with prednisolone produced a moderate decrease in the blood pressure, but additional treatment with antihypertensive drugs was needed to make him normotensive. All three patients were originally thought to have a 21-hydroxylase deficiency and the correct diagnosis of an 11β-hydroxylase deficiency was first established between the age of 26 and 33 years. It is concluded that an early diagnosis and an uninterrupted treatment with glucocorticoids are important in order to prevent hypertension and infertility problems.
Fludrocortisone suppression test in normal subjects, in patients with essential hypertension and in patients with various forms of aldosteronism
Authors: Lund Jens Otto , Nielsen Meta Damkjær
Published: December 2008

The response of urinary diurnal tetrahydroaldosterone (TH-aldo) excretion to fludrocortisone administration (0.3 mg q.i.d. for 3 days) was studied. In normal subjects (n = 13) and in patients with essential hypertension (n = 8), urinary TH-aldo decreased to 36 per cent (range 19–48) and to 51 per cent (range 33–61) of the control value, respectively.

Twenty-four patients with primary aldosteronism were studied. Twenty-two of these showed no significant suppression of urinary TH-aldo in that the excretion of TH-aldo was 79 per cent of the control value or more. Nineteen of these patients were submitted to operation, and an adrenal aldosterone-producing adenoma was disclosed in every single case. Two patients with primary aldosteronism demonstrated a significant suppression of aldosterone production to 62 and 68 per cent, respectively. Adrenal micronodular hyperplasia was verified in one case and suspected in the other.

A significant suppression of aldosterone production was observed in 4 of 5 patients with aldosteronism and normal or high plasma renin levels.

The combination of low plasma renin and autonomy of aldosterone production offers a high degree of certainty for the presence of an aldosterone-producing adenoma.
Effects of oestradiol and progesterone on the alkaline phosphatase activity of a human endometrial cancer cell-line
Authors: Suzuki Mitsuaki , Kuramoto Hiroyuki , Hamano Mieko , Shirane Hideo , Watanabe Keiichi
Published: December 2008

The alkaline phosphatase (ALPase) activity of a human endometrial caner cell-line, established and designated as HEC-50-B in our laboratory, was investigated biochemically and histochemically in relation to its cell growth pattern and to the effects of the sex steroid hormones, oestradiol and progesterone. The ALPase activity increased sharply in the early stationary phase to reach an activity almost 2.5 times higher than that obtained in earlier stages of the culture. On administration of oestradiol to the culture medium, a sharp elevation of the ALPase activity was induced on an average of 2 days earlier (late logarithmic phase) than in the case of an ordinary culture (no hormone administration), without causing a notable change in cell growth pattern. It should be noticed, however, that progesterone at such a low concentration that had very little effect on cell growth in the culture could clearly prohibit the elevation of ALPase activity. This hormonal effect on the ALPase activity resembled that on the enzyme activity of the endometrium of adult women. The ALPase activity of both the cultured endometrial cancer cells and the endometrium was found to be a sensitive indicator of the effect of progesterone. It would be a useful tool for future study in elucidating the mechanism of hormonal control of the neoplasm.
The rise of plasma ACTH induced by ether is mediated through neural pathways entering the medial basal hypothalamus
Authors: Kárteszi M. , Makara G. B. , Stark E.
Published: December 2008

The effect of ether stress on the release of immunoreactive ACTH was studied in rats with an antero-lateral cut around the medial basal hypothalamus. Ether failed to raise the plasma ACTH level of rats in which an antero-lateral hypothalamic cut and adrenalectomy had been performed 7 to 8 days previously. Plasma ACTH was also unchanged in rats exposed to ether 2 h after an antero-lateral cut. These data suggest that intact neural pathways entering the medial basal hypothalamus from the antero-lateral direction are necessary for the ACTH releasing action of ether stress.
A new pharmacological approach to the diagnosis of hyperprolactinaemic states: the nomifensine test
Authors: Genazzani Andrea R. , Camanni Franco , Massara Ferdinando , Picciolini Enrico , Cocchi Daniela , Belforte Luisa , Müller Eugenio E.
Published: December 2008

The prolactin-(Prl) lowering effect of nomifensine (Nom), an antidepressant drug which activates dopamine (DA) neurotransmission mainly by inhibiting DA re-uptake in the central nervous system (CNS), was investigated in normoprolactinaemic subjects, in subjects with physiological puerperal hyperprolactinaemia or pathological hyperprolactinaemia. Nom (200 mg po) administered to 23 normoprolactinaemic women induced a significant decrease in baseline Prl, which was more marked (about 50% inhibition at 120 min) and prompt (30 min) in the subjects who had 'high' Prl levels (>12<20 ng/ml) (13 subjects) than in those with 'low' Prl levels (≤ 12 ng/ml). Also in 9 puerperal women (postpartum day 2) oral administration of 200 mg Nom was followed by a clear-cut decrease of base-line Prl, which started at 30 min and reached nadir values at 150–180 min (about 60% inhibition). Administration of Nom (200 mg po) to 47 subjects with pathological hyperprolactinaemia evidenced the presence of Nom non-responder (36 cases) or responder (11 cases) subjects. In 22 of the Nom non-responder subjects the existence of a Prl-se creting pituitary tumour was established at surgery by selective removal of an adenoma via the transsphenoidal route; of the 14 subjects who did not undergo surgery, 1 had evident and 5 had minor alterations of the sella turcica and, in addition, in 3 subjects the duration of amenorrhoea was longer than 5 years. Only 5 subjects of this group had no radiological alterations of the sella turcica, in presence of basal Prl levels ranging between 50–126 ng/ml. In contrast, 10 out of the 11 Nom-responder subjects had a radiologically normal sella turcica and basal Prl levels lower than 50 ng/ml. Administration of 2-Br-α-ergocriptine (2.5 mg po), a direct stimulant of pituitary DA receptors, to subjects with pathological hyperprolactinaemia (39 cases) induced a striking fall in plasma Prl levels (about 80% inhibition at 240 min), irrespective of the type of Prl responsiveness to Nom.

These results indicate that Nom lowers plasma Prl levels in both normoprolactinaemic and hyperprolactinaemic subjects; in the latter, by virtue of its ability to affect selectively DA neurotransmission in the CNS, the drug appears capable of discriminating between individuals with and without pituitary adenoma.
The effects of iopodate on the serum iodothyronine pattern in normal subjects
Authors: Beng C. G. , Wellby M. L. , Symons R. G. , Stuart Sandra , Marshall Janet
Published: December 2008

The ingestion by normal subjects of 3 g of sodium iopodate, which is widely used in routine oral cholecystography, resulted in significant decreases of serum total and free T3 to a nadir on day 4 which averaged 43% and 40%, respectively, below initial mean values. Total and free rT3 increased markedly to a peak on day 3, 244% and 189%, respectively, above initial mean values. Total and free Ti and free T4 index rose to a maximum on day 4, but these changes were not statistically significant. A marked TSH increase was also seen, most evident on day 3. All these changes reverted to baseline values by day 14 at a time when serum total iodide was still markedly elevated. It is concluded that the changes observed after iopodate were not due to alterations in serum binding proteins nor to an effect on thyroid gland by the large iodine component of iopodate, but were consistent with an effect on the peripheral metabolism of T4. Difficulty in ipterpreting routine thyroid function tests may occur for up to 14 days after oral cholecystography with iopodate.
Insulin release and carbohydrate tolerance in hyperthyroid patients during non-selective or selective β-l-adrenoceptor blockade
Authors: Nilsson Ove R. , Kågedal Bertil , Tegler Lennart
Published: December 2008

The insulin release and the glucose disappearance rate (K-value) during an iv glucose tolerance test were evaluated in 20 hyperthyroid patients before and during treatment with either a non-selective (propranolol, n = 10) or a selective (metoprolol, n = 10) β-l-adrenoceptor blocking agent. Mean daily doses were 240 mg of propranolol and 280 mg of metoprolol, administered four times daily for 10 to 14 days. The insulin increase after glucose injection remained unchanged during treatment with each drug. Fasting blood glucose concentrations and the K-values were not altered during treatment.

Sixteen patients were re-investigated 10 to 36 weeks later when euthyroid due to treatment by surgery, thyrostatic drugs or radioiodine. In the euthyroid state mean serum insulin concentrations after the glucose load were not significantly different from the values found when the patients were hyperthyroid. However, mean fasting blood glucose concentrations decreased from 5.5 mmol/l to 5.0 (P < 0.01) and the mean K-value increased from 1.5 to 2.0 (P < 0.05) when the patients were euthyroid.

It is concluded that short-term treatment of hyperthyroid patients with non-selective or selective β-l-adrenoceptor blocking agents does not impair the glucose stimulated insulin secretion or the carbohydrate tolerance.
Parathyroid hormone release from the perfused canine thyroid-parathyroid complex isolated in situ
Authors: Pedersen Bjarne Bach , Laurberg Peter , Christensen Merete Sanvig , Nielsen Stig Pors
Published: December 2008

A model for direct measurement of hormone release from the canine parathyroid gland is described. The two separate thyroid-parathyroid gland complexes were isolated in situ and perfused independently using a synthetic medium with a welldefined concentration of ionized calcium (Ca++). The concentration of parathyroid hormone (PTH) in the effluent was measured by radioimmunoassay, using an antiserum to bovine PTH that cross-reacts with canine PTH. Displacement curves of dilutions of effluent samples were similar to those of bovine PTH (1–84). During infusion of 1.49 mmol/l Ca++ the PTH release was constant for more than 4 h. Variations in Ca++ from 1.56 to 1.15 or 2.15 mmol/l induced rapid and sustained stimulation or suppression of PTH release. The retained ability of the preparation was ascertained by recording the response to infusion of calcium free medium at the end of each experiment.
The role of insulin absorption and sensitivity in determining a diabetic's daily insulin dosage
Authors: Asplin C. M. , Hartog M. , Goldie D. J. , Smythe P. , Alberti K. G. M. M.
Published: December 2008

The change of serum free and total insulin, and of blood intermediary metabolites, growth hormone and cortisol have been determined after separate tests using 0.3 units/kg 'Actrapid MC' given by sc injection and 0.04 units/kg/h by iv infusion in 16 fasted chronic-bovine-insulin-treated diabetics. Eight of these diabetics normally received 32 units or less of conventional, mainly bovine insulin a day and the other eight 128 units or more. Paradoxically the high dose group had a greater fall (5.6 V 3.1 mmol/l; P < 0.05) in blood glucose four h after the sc insulin injection despite similar pre-insulin values (8.2 and 6.9 mmol/l respectively). Otherwise the responses were markedly similar in the two groups to both sc and iv insulin. Thus the gross differences in daily insulin dosage could not be explained in terms of insulin absorption or sensitivity as assessed by several metabolic parameters.
Beta-cell function and metabolic control in insulin treated diabetics
Authors: Madsbad S. , McNair P. , Faber O. K. , Binder C. , Christiansen C. , Transbø I.
Published: December 2008

In a random one day study beta-cell function was evaluated in 210 insulin treated diabetics by the serum C-peptide concentration 6 min after iv injection of 1 mg of glucagon. Sixty-five patients (31%) had residual beta-cell function. As a group these patients were characterized by having a higher age at onset of diabetes (P < 0.01), a shorter duration of disease (P < 0.01) and by receiving a smaller dose of insulin (P < 0.01). However, their quality of metabolic control did not differ from the patients without beta-cell function. Although the concentrations of post-stimulatory C-peptide correlated inversely with both the 24-hour glycosuria (P <0.01) and the fasting blood glucose concentrations (P < 0.02), only a subgroup with C-peptide concentrations exceeding 0.30 pmol/ml showed a definitely better degree of metabolic control than those without beta-cell function. As this subgroup also received the smallest dose of insulin these observations suggest that maintenance of beta-cell function above this level facilitates good metabolic control.

Evidence is presented suggesting that measurements of the 24-hour glycosuria undertaken in a diabetes clinic create a too optimistic impression of the quality of metabolic control during every day life.
Diurnal change of serum androstenedione and testosterone and response to hCG and dexamethasone in women with polycystic ovaries, adrenal hyperandrogenism and unexplained hirsutism
Authors: Lisse K. , Schürenkämper P. , Friedrich W. , Rutkowsky J.
Published: December 2008

The diurnal change in peripheral serum concentration of androstenedione (A) and testosterone (T) and their response to dexamethasone (DXM) and hCG was measured in 6 women with unexplained hirsutism (H), and the results compared to those from 4 women with proven polycystic ovaries (PCO) and 3 women with proven adrenal hyperandrogenism (AHA). The DXM suppression study was performed on the basis of short-term tests measuring the change in the steroid levels after iv infusion of 20 mg DXM. Response to hCG was assessed by measurement of steroids in serum collected before and for 5 days after im administration of 10 000 IU hCG. The AHA group showed a greater diurnal change than the PCO and the H group. The mean post-administration levels of A and T following DXM infusion in the AHA group were relatively lower than the levels found in both the PCO group (P < 0.05 for A, P < 0.10 for T) and the H group (P < 0.05 for A, P < 0.01 for T), but were not different between the PCO and H group (P < 0.80 for A, P < 0.20 for T). The mean post-administration levels of these androgens following hCG injection in both the PCO group (P < 0.02 for A, P < 0.01 for T) and the H group (P < 0.10 for A, P < 0.10 for T) were relatively higher than the levels found in the AHA group. These results suggest that in most women with unexplained hirsutism normal-sized ovaries are the source of excessive androgens.
Glycine stimulates growth hormone release in man
Authors: Kasai Kikuo , Suzuki Hitoshi , Nakamura Tsutomu , Shiina Hiroaki , Shimoda Shin-Ichi
Published: December 2008

The influence of glycine, the simplest amino acid, on pituitary function has been investigated in the present study.

Different doses (4, 8 or 12 g) of glycine were intravenously infused over 15 or 30 min in normal subjects. Serum levels of GH (growth hormone) and Prl (prolactin) were measured before and after the infusion, and also blood sugar levels were determined.

The dose of 4 or 8 g glycine induced a significant increase in serum GH (P < 0.05 or P< 0.001, respectively); however, a more pronounced and significant increase in serum GH levels was observed after infusion at a dose of 12 g glycine (P < 0.001). It was clearly observed that the dose-dependent GH release to intravenous glycine occurred in normal subjects. On the contrary, serum Prl level was not changed significantly, and blood sugar level was transiently, but significantly (P < 0.05), increased after the infusion of 12 g glycine.

The present data suggest that glycine might play an important role in the control of hypothalamic-pituitary function.
Somatomedin and analogues of cyclic AMP increase the number of cells synthesizing DNA in cartilage from hypophysectomized rats
Authors: Hough Aubrey , Bomboy James D. , Salmon William D.
Published: December 2008

The effects of somatomedin and certain nucleotides on nuclear labelling of cartilage cells with [3H] thymidine were determined by autoradiography. Segments of costal cartilage from hypophysectomized rats were incubated for 24 h in a basal medium with or without additions and then pulsed for 2 h with [3H]thymidine in the basal medium. Both somatomedin (0.1 U/ml) and Bt2cAMP (10−4m) increased the number of labelled nuclei, and the combined effects were more than additive. A parallelism between the effects of these agents on nuclear labelling and their effects on total thymidine incorporation into DNA was demonstrated. The 8-bromated derivative of cAMP (10−4m) also enhanced chondrocyte nuclear labelling, but neither 8-Br5'-AMP (10 −4m) nor 8-Br-cGMP (10−4m) exhibited actions of the cAMP analogues. It is concluded that in cartilage obtained from hypophysectomized rats and incubated under the specified conditions (1) both somatomedin and cAMP analogues increase the number of cells synthesizing DNA as well as total thymidine incorporation into DNA, (2) the effects of the hormone and cyclic nucleotide in combination are synergistic, and (3) the increased incorporation of labelled thymidine into DNA reflects increased DNA synthesis and not merely an alteration of the specific activity of the intracellular thymidine nucleotide pool.
Serum prolactin responses to metoclopramide in Cushing's syndrome and Nelson's syndrome
Authors: Kasperlik-Zaluska Anna A. , Jeske Wojciech
Published: December 2008

Serum prolactin (Prl) levels in basal conditions and those following metoclopramide administration (10 mg orally) were determined in 10 women with Cushing's syndrome, 9 patients bilaterally adrenalectomized for adrenal hyperplasia without clinical evidence of a pituitary tumour, and one after adrenal adenoma removal, 8 women with Nelson's syndrome and 12 normal subjects. Blood samples were taken at 1 and 2 h after metoclopramide administration.

In patients with hyperadrenocorticism the Prl responsiveness was reduced compared into the bilaterally adrenalectomized patients and the control group. In the bilaterally adrenalectomized patients without features of a pituitary adenoma, Prl responses to metoclopramide were significantly higher than those in the remaining subjects under investigation. In the patients with Nelson's syndrome mean baseline Prl was higher than that in the other groups studied; serum Prl responses to metoclopramide were significantly lower than those in the bilaterally adrenalectomized patients with no evidence of a pituitary tumour.

These results indicate that: 1) hypercortisolaemia of Cushing's disease diminishes Prl responses to metoclopramide, 2) the elimination of hypercortisolaemia by adrenalectomy results in a hyperresponsiveness of serum Prl to metoclopramide, 3) the development of Nelson's tumours is associated with increased baseline Prl and with significantly lower Prl responses to metoclopramide compared with those found in the other patients adrenalectomized for Cushing's syndrome, without clinical evidence of a pituitary adenoma.
Effects of intraventricular injection of Sar1-Ala8-angiotensin II on plasma vasopressin level increased by angiotensin II and by water deprivation in conscious rats
Authors: Yamaguchi K. , Hama H. , Sakaguchi T. , Negoro H. , Kamoi K.
Published: December 2008

The effects of intraventricular injection of Sar1-Ala8-angiotensin II (a specific antagonist of angiotensin II) on the plasma vasopressin level increased by intraventricular injection of angiotensin II and by water deprivation (46 h) were examined in conscious male rats with an indwelling cannula in the third cerebral ventricle. Blood samplings were made by decapitation and the plasma level of vasopressin was determined by radioimmunoassay. Twenty-five, 50 or 100 ng of angiotensin II produced significant (P<0.05) increase in plasma vasopressin level 90 sec after the injection. The effect of 50 ng of angiotensin II was inhibited significantly (P<0.05) at least with 100 ng of Sar1-Ala8-angiotensin II given 2 min before the injection of angiotensin II. The dehydrated rats to which 1000 ng of Sar1-Ala8-angiotensin II was given 5 min before the decapitation showed the significantly (P<0.05) lower median plasma vasopressin level than that of the dehydrated controls. No significant difference in plasma osmolality was noted between them. These results suggest that the plasma vasopressin response to intraventricular angiotensin II is produced via angiotensin II receptors in the brain and that Sar1-Ala8-angiotensin II inhibits the effect of endogenous angiotensin II on plasma vasopressin level under dehydration.
Oral administration of TRH in puerperal women: effect on insufficient lactation, thyroid hormones and on the responses of TSH and prolactin to intravenous TRH
Authors: Ylikorkala O. , Kivinen S. , Kauppila A.
Published: December 2008

Thirteen puerperal women with insufficient lactation were treated with thyrotrophin releasing hormone (TRH) 20 mg twice daily for two weeks. Intravenous (iv) TRH stimulation tests were done before the TRH therapy and within 3–5 h after the last dose of oral TRH. Plasma samples were assayed for prolactin (Prl), thyrotrophin (TSH), triiodothyronine (T3) and thyroxine (T4) by radioimmunoassays, and the lactational response was objectively monitored in 11 women. Oral TRH treatment was associated with significantly (P < 0.05) depressed Prl levels (23.0 ± 7.9 μg/l vs. 61.4 ± 26.2, mean ± sem), no change in TSH levels (3.7 ± 0.4 IU/1 vs. 4.0±0.4) but significantly (P<0.01) elevated T3 (2.17±1.14 nmol/l vs. 1.83 ± 0.09) and T4 (131.6 ± 7.9 nmol/l vs. 96.6 ± 5.8) levels. Oral TRH entirely blocked the TSH response and significantly (P<0.01) blunted the Prl response to iv TRH stimulation. No improvement in lactation was observed.
Increased plasma pancreatic polypeptide (PP) in diabetic ketoacidosis; normalization following treatment
Authors: Skare S. , Hanssen K. F. , Lundqvist G.
Published: December 2008

As both hypoglycaemia and hyperglycaemia may modify plasma levels pancreatic polypeptide (PP), we measured plasma PP by a homologous radioimmunoassay in seven diabetics who were admitted to the hospital in overt diabetic ketoacidosis (initial blood glucose 27.1–55.0 mmol/l). None had circulating PP-antibodies. All were treated with continuous infusion of insulin and fluids.

Before starting treatment, plasma PP ranged from 2585–136 pmol/l (mean 629 pmol/l). Following treatment plasma PP decreased gradually in all patients. The following morning mean plasma PP was 242 pmol/l, 67 pmol/l when one uraemic patient was excluded. The normal value is less than 100 pmol/l.

This study shows that plasma PP is clearly elevated in diabetic ketoacidosis and decreases following treatment.
Ontogeny and immunoreactive forms of vasoactive intestinal peptide (VIP) in rat brain
Authors: Maletti M. , Besson J. , Bataille D. , Laburthe M. , Rosselin G.
Published: December 2008

Immunoreactive vasoactive intestinal peptide (IR-VIP) was assayed in rat brain between day 17 postcoitum (pc) and day 60 post-partum (pp). IR-VIP was detectable at day 17 pc (0.1 ± 0.01 pmol/organ), increased up to day 20 pp (142 ± 13.6 pmol/organ) and then reached a plateau up to day 60 pp (140 ± 14 pmol/organ). On a concentration basis, IR-VIP increased slightly during the perinatal period and rose more sharply between day 8 pp (17.2 ± 0.09 pmol/g of wet weight) and day 20 pp (105 ± 10 pmol/g of wet weight). Thereafter, the concentration decreased slowly up to day 40 pp (81.2 ± 12 pmol/g of wet weight) and day 60 pp (69.7 ± 6.9 pmol/g of wet weight). Ion-exchange chromatographic separation of extracts from rat brain obtained by two different procedures indicated the presence of two forms of VIP-like components measured in column effluents by both radioimmunoassay and radioreceptorassay. One molecular form emerged in a similar position to intestinal porcine VIP and was equally effective in radioimmunoassay and radioreceptorassay using rat liver membranes. Another component, which emerged after ion-exchange chromatography in front of porcine VIP, had on a Sephadex G-50 superfine column an elution position identical to that of intestinal porcine VIP. The immunoreactivity of the latter was significantly higher than the biological activity; it could thus be a deamidated form of VIP.
Plasma 11-deoxycortisol, androstenedione, testosterone and ACTH in comparison with the urinary excretion of tetrahydro-11-deoxycortisol as indices of the pituitary-adrenal response to oral metyrapone
Authors: de Lange W. E. , Sluiter W. J. , Pratt J. J. , Doorenbos H.
Published: December 2008

Plasma levels of ACTH, 11-deoxycortisol, androstenedione and testosterone and urinary tetrahydro-11-deoxycortisol were determined during a two day oral metyrapone test using doses of 1.5 g every 6 h. The level of 11-deoxycortisol 48 h after the start was distinctive regarding the assessment of pituitary ACTH secretory capacity. The rise of androstenedione concentration after 48 h is distinctive in a similar way, whereas ACTH determination is of little diagnostic value in this respect. Further, an increase in testosterone level can be observed in cases of low basal testosterone production. This increase is probably the result of peripheral conversion of androstenedione to testosterone. Where the basal testosterone concentration was high, no change could be measured.
Potentiation of sulpiride-induced prolactin secretion by sodium deprivation in man
Authors: Mori Masatomo , Kobayashi Isao , Ohshima Kihachi , Maruta Sakae , Shimomura Yohnosuke , Fukuda Hitoshi
Published: December 2008

Previous studies suggest that prolactin is not an important osmoregulatory hormone in man, while aldosterone is well known to be important in osmoregulation. The present investigation was undertaken to ascertain whether serum osmotic changes affect pituitary prolactin secretion following sulpiride administration. Five normal subjects were placed on a constant isocaloric diet with different sodium content. Serum prolactin and aldosterone level were measured by specific radioimmunoassay. The basal serum level of prolactin was unaffected by changes in sodium content of the diet, in contrast to the basal level of aldosterone. On the other hand, the maximum levels of serum prolactin in response to sulpiride (50 mg, im) were significantly higher on a low sodium diet (3 g of salt/day) than on a control diet (12– 15 g of salt/day). When the content of diet changed from low salt to high salt (25 g of salt/day), sulpiride-induced prolactin response decreased, though it was not significantly lower than that on a control diet. However, sulpiride administration could not stimulate aldosterone secretion under any of the various sodium contents of the diet.

The present study provides evidence that lowering of serum osmolarity stimulates serum prolactin response to sulpiride administration in man and this response is not modulated by aldosterone secretion.
Hormonal profile of the cycle in 68 normally menstruating women
Authors: Landgren B.-M. , Undén A.-L. , Diczfalusy E.
Published: December 2008

The peripheral plasma levels of immunoreactive LH, FSH, oestradiol and progesterone were analyzed daily throughout the cycle in 68 normally menstruating women, exhibiting a cycle length of 25 to 36 days during the period of blood sampling. The (geometric) mean length of the follicular phase was 15 days, with an individual variation between 9 and 23 days. The mean length of the luteal phase was 13 days, with an individual variation between 8 and 17 days. The mean ratio of the length of the follicular to luteal phase (F/L ratio) was 1.13, and 62 of 68 subjects (91%) exhibited an F/L ratio between 0.75 and 1.80. In one-third of the cycles studied. the pre-ovulatory oestradiol and LH peaks occurred before the 12th, or after the 18th day of the cycle, and the length of the luteal phase was shorter than 12, or longer than 15 days.

The length of the follicular phase was positively correlated to the mean LH level of days LH-7 to LH-3 before the midcycle surge (P< 0.001) and negatively correlated to the mean oestradiol level of the first 6 days of the cycle (P< 0.001) and to the height of the preovulatory oestradiol peak (P<0.01). There was also a positive correlation between the length of the entire cycle and the mean LH level throughout the cycle (P< 0.01) or during days LH-7 to LH-3 (P < 0.001), or the height of the midcycle LH surge (P<0.01), and a negative correlation between cycle length and the mean oestradiol level of the first 6 cycle days (P < 0.001), or of the entire follicular phase (P < 0.001), or of the complete cycle (P < 0.01). Hence a combination of high initial oestradiol levels with low LH levels is associated with relatively short cycles and the opposite combination with relatively long ones.

In agreement with previous findings in 32 normally menstruating women, 94%, or 64 of the 68 subjects of the present study had plasma progesterone levels higher than 16 nmol/1 for a minimum of 5 days. Hence, progesterone levels lower than this value or exceeding this value for a shorter period than 5 days are considered to reflect an insufficient or partially suppressed luteal function.

In addition, 62 of the 68 subjects studied (91%) fulfilled a series of criteria concerning the minimal and maximal levels of LH, FSH, oestradiol and also progesterone during different cycle phases. It is suggested that these criteria together with the progesterone levels indicated above are characteristic of a normal ovulatory cycle, at least in the local population. The acquisition of similar 'critical levels' in other populations may provide a useful approach towards the establishment of generally accepted criteria for distinguishing a normal from an abnormal cycle.
Zinc induced changes in the progesterone binding properties of the human endometrium
Authors: Habib F. K. , Maddy S. Q. , Stitch S. R.
Published: December 2008

The binding of progesterone to plasma and endometrial cytosol is markedly influenced by Zn++, the degree and magnitude of this influence being dependent on the concentration of the metal ion. There is a critical protein concentration (approximately 10 mg/ml) beyond which the zinc exerts either a stimulatory or inhibitory effect.

Maximum increases in binding of over 60% were attained in solutions of plasma containing 30 mg of protein whereas increases of 10% were measured in cytosol specimens with 10 mg protein/ml. This metal mediated effect was however progressively diminished with increasing zinc concentration resulting finally in the return of the binding to the levels observed in the absence of added Zn++.

The zinc induced inhibition was most evident in plasma and cytosol with a protein concentration less than 10 mg/ml. The magnitude of this effect was inversely proportional to the levels of protein in solution.

Scatchard analysis of the the data revealed that the number of progesterone bindings sites in the receptor are affected by the presence of the metal while the association constants remained unchanged. The study also suggests that the zinc induced changes are partially reversed by dithiothreitol and EDTA. We believe that the metal interferes directly with the SH groups at the receptor binding sites.
The development of the pituitary-adrenal axis in the guinea pig
Authors: Jones Colin T. , Roebuck Margaret M
Published: December 2008

The concentration of cortisol and ACTH in the umbilical vein plasma of the foetal guinea pig has been measured over the later half of gestation. Between 55–60 days there is a large increase in the concentration of both. Injection of ACTH1-24 into the foetal guinea pig elicits a relatively small increase in plasma cortisol at 46–55 days, a somewhat greater response at 56–60 days and a large response at 61–66 days. Between 47–55 days and 58–63 days cells prepared from the foetal adrenal show a large increase in their responsiveness to ACTH stimulation as measured by cortisol and androstenedione output. However, there was no clear difference in responsiveness between 58–60 days and 61–63 days. Thus between 56–60 days the foetal adrenal appears less responsive to ACTH stimulation in vivo than in vitro. ACTH in the circulation of the guinea pig is present in high-molecular-weight and low-molecular-weight forms and the ratio of concentration of ACTH1-39 to that of the high-melcular-weight forms rises after 60 days. It is proposed that this is an important factor in inducing an increased steroid response from the foetal adrenal.
Effects of high dose oestrogen and testosterone treatment in adolescents upon trabecular and compact bone measured by 125I computed tomography. A preliminary study
Authors: Exner Gerhard Ulrich , Prader Andrea , Elsasser Urs , Anliker Max
Published: December 2008

125I Computed Tomography (CT) allows for the selective determination of trabecular and compact bone mineral parameters in the radius. Using this technique the effects of high dose oestrogen treatment in 11 tall girls, and of high dose testosterone treatment in 5 tall boys were monitored. In both groups trabecular bone density (TBD) increased steadily during treatment at a rate of about 1% per month. Also in both groups the compact bone mineral increased steadily. These results are compared with those from a cross sectional study on 49 normal children and 36 normal adults, in whom TBD was found to be independent of age and sex, so that the increases in TBD in both treatment groups can be attributed directly to the influence of the sex hormones. Since the compact bone mineral is higher in adults than in children it cannot yet be decided whether the increases seen in the treated patients are related to the sex hormone treatment, or reflect only the normal development of the bone during adolescence.