bluuebunny/crossref_metadata_2025 huggingface dataset:
Thyroid stimulating immunoglobulins in Graves' disease with goitre growth, low thyroxine and increasing triiodothyronine during PTU treatment
Authors: Hegedüs Laszlo , Hansen Jens M. , Bech Karine , Kampmann Jens P. , Jensen Keld , Andersen Elo , Hansen Palle , Karstrup Steen , Bliddal Henning
Published: December 2008

Abstract. In 50 consecutive patients with Graves' disease treated with PTU, 7 (group 1) developed increasing goitre in spite of unmeasurable TSH. Thyroid variables were compared with those from 10 controls with an ordinary response to PTU (group 2). Serum T4 decreased in group 1 from 246 ± 47 nmol/l (mean ± sd) to 40 ± 9 nmol/l after 6 weeks of PTU treatment and continued to be below the normal range during the next 4 months. In group 2 serum T4 decreased from 190 ± 35 to 88 ± 47 nmol/l and stayed in the normal range. Serum T3 was normalized in both groups after 6 weeks but increased to values above the normal range in group 1 after that time. In spite of unmeasurable TSH during the 6 months of treatment in group 1, thyroid volume, determined ultrasonically, increased significantly from 60 ± 29 to 93 ± 68 ml (P < 0.05), but was unaltered in group 2 about 25 ml.

Thyroid stimulating antibodies (TSAb) measured by adenylate cyclase activation (normal below 109%) decreased in group 2 from 117 ± 23 to 90 ± 17% (P <0.01) (6 months of therapy), but increased significantly in group 1, from 201 ± 47% to a maximum value of 234 ± 69% (P < 0.05). TSH binding inhibitory immunoglobulins (TBII) (given as per cent inhibition, normal below 26%) decreased in group 2 from 43 ± 29 to 29 ± 27% (P < 0.05) but were unaltered high in group 1,66 ± 25% before therapy and 57 ± 26% after 6 months of therapy. A positive correlation was found between thyroid volume and TSAb and TBII levels (P < 0.05, P < 0.05) before treatment as well as during the treatment period of 6 months. In 5 of 7 patients of group 1 either 131I therapy or subtotal thyroidectomy were necessary to control the disease.

It is proposed that TSAb and TBII remaining abnormal in this subgroup of patients with Graves' disease, might in part explain the unusual response to PTU-treatment.
Changes in thyroxine monodeiodination in rat liver, kidney and placenta during pregnancy
Authors: Yoshida Katsumi , Suzuki Michiko , Sakurada Toshiro , Kitaoka Hirofumi , Kaise Nobuko , Kaise Kazuro , Fukazawa Hiroshi , Nomura Takashi , Yamamoto Makiko , Saito Shintaro , Yoshinaga Kaoru
Published: December 2008

Abstract. Monodeiodination of thyrxoine (T4) was studied in the liver, kidney and placenta of pregnant rats. Age matched female non-pregnant and pregnant Sprague-Dawley rats on the 7th, 14th, 17th and 21st days of gestation were used. The 800 × g supernatants of tissue homogenates (protein 1 mg/tube) were incubated with 1 μg of stable T4 in the presence of 5 mm dithiothreitol (DTT) at 37°C for 60 min at pH 7.5. Net triiodothyronine (T3) generation from T4 in rat liver homogenates on the 7th day of gestation was significantly lower than that in the non-pregnant rat. Thereafter it increased, but values on the 14th, 17th and 21st days of gestation were not significantly different from those obtained in the non-pregnant rat. Net renal T3 generation from T4 on the 14th day was significantly lower than that in the non-pregnant rat. It was increased thereafter and the values at the 17th and 21st days of gestation were not significantly different from those in the non-pregnant rat. Net reverse T3 (rT3) generation from T4 in the placenta rose from the 14th to the 17th day and then dropped by the 21st day and the value at the 17th day was significantly higher than those at the 14th and 21st days of gestation. These results indcate that 1) both T4 outer-ring monodeiodination in the pregnant rat liver and kidney, and T4 inner-ring monodeiodination in the placenta show significant variation with the progress of gestation; 2) the time course of the T4 outer-ring monodeiodination in pregnant rat liver and kidney is completely different from T4 inner-ring monodeiodination in the placenta.
6-methoxy-tetrahydro-β-carboline (pinoline): effects on plasma renin activity and aldosterone, TSH, LH and β-endorphin levels in rats
Authors: Airaksinen M. M. , Sainio E.-L. , Leppäluoto J. , Kari I.
Published: December 2008

Abstract. Plasma renin activity and the plasma concentrations of aldosterone, TSH, LH and β-endorphin were radioimmunologically determined in rats after ip administration of 15 mg/kg of 6-methoxy-tetrahydro-β-carboline (6-MeO-THBC, pinoline), a compound found to occur normally in mammalian and avian pineal gland. A 2.6-fold increase of plasma aldosterone concentration was found and it was preceded by increase of plasma renin activity. An increase was also found in β-endorphin/β-lipotrophin concentration while TSH and LH concentrations did not change significantly. The present results do not prove nor exclude the concept that 6-MeO-THBC is the 'adrenoglomerulotropin'. The effects of 6-MeO-THBC on plasma β-endorphin/β-lipotrophin levels may be mediated by the dopaminergic or 5-HT-neurones.
Effects of pregnant mare's serum gonadotrophin administered in vivo on steroid accumulation by isolated rabbit ovarian follicles
Authors: YoungLai E. V.
Published: December 2008

Abstract. Various doses (5, 50 and 100 IU) of pregnant mare's serum gonadotrophin (PMS) were administered to sexually mature female rabbits and steroids measured in follicular fluid, ovarian pieces and in incubation media of isolated follicles treated with ovine luteinizing hormone (LH). Follicular fluid progesterone, oestradiol and androgen were increased after PMS injection. Ovarian progesterone content was increased by all doses of PMS, and androgen and oestradiol content only by 50 and 100 IU PMS. Medium sized follicles from rabbits treated with 50 and 100 IU PMS accumulated more progesterone than all follicles from rabbits treated with saline or 5 IU PMS. Androgen accumulation by small follicles from 50 and 100 IU dose rabbits was higher than that by follicles from other treatment groups. Oestradiol accumulation mimicked androgen accumulation. The addition of LH to the medium stimulated the accumulation of progesterone and androgen by all follicles. LH caused an increase in oestradiol accumulation by medium follicles from saline and low dose PMS treated animals. No effect of LH on oestrogen accumulation was seen with large or medium follicles from animals treated with 100 IU PMS or 50 IU PMS for 2 or 3 days. These results suggest that priming of small follicles with PMS can increase their ability to produce androgen which is probably aromatized to oestrogen.
Impairment of adrenergic-induced proopiomelanocortin-related peptide release in heroin addicts
Authors: Facchinetti Fabio , Volpe Annibale , Nappi Giuseppe , Petraglia Felice , Genazzani Andrea R.
Published: December 2008

Abstract. The effects of iv stimulation with clonidine on plasma levels of β-lipotropin (β-LPH), β-endorphin (β-EP), cortisol, growth hormone (GH) and adrenocorticotrophic hormone (ACTH) were tested in a group of 10 healthy volunteers and in 8 heroin abusers.

Hormones were measured either by direct radioimmunoassay (RIA) (GH, cortisol) or after plasma extraction and Sephadex G-75 column chromatography (β-LPH and β-EP) or by immunoradiometric assay (IRMA) (ACTH). Plasma levels of GH increased in a similar fashion in the two groups. In the controls, clonidine induced release of β-LPH and β-EP after 30 min (from 8.9 ± 1.0 to 19.1 ± 4.6 fmol/ml, P < 0.01 and from 8.1 ± 0.6 to 17.9 ± 4.6, P < 0.01) and of ACTH after 60 min (from 12.1 ± 1.8 to 18.1 ± 1.8, P < 0.05) while in addicts β-EP but not β-LPH showed a significant increase (from 8.5 ± 0.7 to 19.8 ± 4.2, P < 0.05), 90 min after the injection.

In heroin addicts, plasma cortisol levels decreased continuously after clonidine stimulation while in controls they showed a biphasic pattern, decreasing until the 60th min (from 135.2 ± 30.4 ng/ml to 74.0 ± 13.3, P < 0.05) and regaining basal levels 1 h later (122.0 ± 24.8, P < 0.05 vs 60th min value).

These data demonstrate the existence in human beings of noradrenergic control of proopiomelanocortin (POMC)-related peptides and indicate that chronic opiate abuse greatly interferes with this control.

Clonidine-induced release of plasma β-EP may be of importance with regard to its therapeutic effects in detoxification.
Hyperglycaemic effect of glucagon administered intracerebroventricularly in the rat
Authors: Marubashi Seijiro , Tominaga Makoto , Katagiri Tadashi , Yamatani Keiichi , Yawata Yoshikazu , Hara Masao , Sasaki Hideo
Published: December 2008

Abstract. The intracerebroventricular (icv) administration of 100 ng glucagon resulted in more prolonged and pronounced elevations of plasma glucose levels than the intravenous injection of 100 ng glucagon. Insignificant changes in plasma IRI and IRG levels after icv glucagon administration contrasted to marked increases in both IRI and IRG levels after the iv injection.

Icv glucagon-induced hyperglycaemia was completely prevented by the prior administration of atropine, phentolamine or hexamethonium, and partially inhibited by bilateral adrenalectomy, but not by propranolol pretreatment. These findings suggested that the hyperglycaemic effect is brought about through cholinergic and α-adrenergic neural pathways and partly via the adrenal medulla.
Progression of cardiovascular disease in acromegalic patients treated by external pituitary irradiation
Authors: Baldwin A. , Cundy T. , Butler J. , Timmis A. D.
Published: December 2008

Abstract. Cardiovascular complications are a major cause of morbidity and mortality in acromegaly and seem to be related to the long duration of the disorder. Conventional external pituitary irradiation for acromegaly produces a consistent, but slow, fall in elevated serum growth hormone (GH) levels. It has not been established whether such treatment is effective in preventing the development of cardiovascular complications. The evolution of cardiovascular disease has therefore been studied in 11 acromegalic patients followed up for a mean 10 years (range 3–17) after external pituitary irradiation. At the final follow-up fasting serum GH were significantly (P < 0.01) lower than pre-irradiation levels, but cardiovascular events (myocardial infarction, dysrhythmias, hypertension, major arterial disease, heart failure) increased significantly in prevalence (P < 0.01) during this period. Electrocardiographic abnormalities also increased in prevalence. At the final follow-up 6 patients had cardiomegalv on chest X-ray and echocardiographs (10 patients) were abnormal in every case. All 11 patients had evidence of complete or partial anterior hypopituitarism. We confirm that external pituitary irradiation is effective in reducing elevated serum GH levels in acromegaly, but suggest that such a slow reduction in serum GH levels does not retard the development of cardiovascular complications.
Effect of iodide treatment on iodine concentration and volume of endemic non-toxic goitre in childhood
Authors: Leisner B. , Henrich B. , Knorr D. , Kantlehner R.
Published: December 2008

Abstract. In a total of 195 children and adolescents of both sex (mean age 12.9, range 5–17 years) with endemic non-toxic goitre the thyroidal iodine concentration (IC) was determined using X-ray fluorescent scanning on admission and during iodine (100 μg daily) and l-thyroxine (3 μg/kg body weight daily) treatment respectively. Additionally the thyroid volume was measured sonographically in a longitudinal study including 46 patients before and after 4–8 months of iodine supplementation (100 μg daily).

The IC was 305 ± 144 μg/g. It compared well with that of adult goitre patients (288 ± 109 μg/g) and was significantly inferior to the value of normal controls (389 ± 170 μg/g). Under l-thyroxine therapy the IC further decreased (243 ± 144 μg/g), whereas patients receiving iodide showed an increase of the IC (570 ± 197 μg/g). The mean TSH level fell from 2.3 ± 0.9 μU/ml to 1.4 ± 0.6 μU/ml. The average T4/TBG (thyroxine binding globulin) ratio showed a slight increase which, however, was not significant.

The mean goitre volume decreased by 40%.

It was evidenced that iodide is useful not only in the prophylaxis of non-toxic goitre but also as a more physiologic treatment than thyroid hormones, at least for young subjects with simple diffuse goitres.
Thyroid carcinoma and thyroiditis in an endemic goitre region before and after iodine prophylaxis
Authors: Harach H. R. , Escalante D. A. , Oňativia A. , Outes J. Lederer , Day E. Saravia , Williams E. D.
Published: December 2008

Abstract. Iodine prophylaxis was introduced to the moderately severe goitre endemic area in Salta, Argentina, in 1963. All thyroidectomies from a 20 year period were reviewed, and 148 thyroid malignancies carefully studied. The period from 5 to 15 years after iodization was associated with a lower frequency of follicular carcinomas and a higher frequency of papillary carcinomas than the period before and up to 5 years after prophylaxis. Lymphoid infiltration in the non-tumorous thyroid was relatively infrequent before iodine prophylaxis: it was much higher in each of the post-prophylaxis periods. These results, in agreement with other studies, support the view that an increased iodine intake is associated with an increased incidence of papillary carcinoma of the thyroid and thyroiditis.
Treatment of myxoedema coma factors associated with fatal outcome
Authors: Hylander Britta , Rosenqvist Urban
Published: December 2008

Abstract. Treatment of myxoedema coma has been associated with a high mortality. The causes of death were analysed in this paper by retrospective study of the records of 11 myxoedema coma patients. The serum thyroxine (T4) and triiodothyronine (T3) levels were estimated retrospectively from the amounts of hormone given to the patients by a two-compartment model. Seven patients died and 4 survived. The patients who died were significantly older (78.9 ± 2.2 years, mean ± sem) than those who survived (66.8 ± 3.7 years). The initial heart rate was lower in the deceased group, but both groups had increased their heart rate on treatment. The surviving patients showed an increase in body temperature during the first 3 days of treatment, in contrast to the patients who eventually died. The deceased patients had received larger amounts of thyroid hormone and had calculated levels of T3 that were nearly twice as high as those of the surviving patients. Old age and a high serum level of T3 are determinants for the fatal outcome of myxoedema coma. Our analysis underscores the importance of using a cautious replacement regimen in myxoedema coma patients.
Prolonged ACTH infusion suppresses aldosterone secretion in spite of high renin activity
Authors: Oelkers W. , Harendt H. , Exner P.
Published: December 2008

Abstract. Five normal young males on a low sodium diet received iv ACTH (1–24) infusions (10 IU/24 h) for 100 h in addition to diuretics. The aim of the study was to find out whether the biphasic effect of ACHT on aldosterone (initial stimulation followed by 'esacpe') could be prevented by keeping plasma renin activity (PRA) at a fairly constant high level. PRA was around 20 ng/kg/min before and towards the end of the ACTH infusion. Plasma aldosterone and aldosterone excretion rates were, nevertheless, only transiently stimulated, but the first was relatively more suppressed than the latter at the end of the ACTH infusion. Plasma 18-OH-corticosterone followed the same pattern. Even on the last infusion day, aldosterone and 18-OH-corticosterone levels were still higher than in normal ambulatory sodium-replete men. The fasciculata steroids cortisol, 11-deoxycorticosterone and corticosterone were continuously stimulated by ACTH.

It is concluded that the biphasic response of zona glomerulosa steroids to ACTH is basically independent of renin and angiotensin II. However, the marked suppression of aldosterone secretion observed in sodium-replete individuals during prolonged ACTH treatment was not seen in this study. Angiotensin II or a different factor associated with sodium depletion may, therefore, partly protect the zona glomerulosa from adverse effects of ACTH observed in the sodium-repelete state.
Trophic effects of potassium loading on the rat zona glomerulosa: permissive role of ACTH and angiotensin II
Authors: Mazzocchi Giuseppina , Rebuffat Piera , Robba Claudia , Malendowicz Ludwig K. , Nussdorfer Gastone G.
Published: December 2008

Abstract. The trophic effects of chronic potassium loading on the rat zona glomerulosa were investigated by morphometric and radioimmunological methods. Potassium loading exerted a potent adrenoglomerulotrophic effect in saline treated control rats, but it was not able to reverse the captopril- and dexamethasone-induced atrophy of the zona glomerulosa. However, if the captopril/dexamethasone administered rats were given maintenance doses of angiotensin II and ACTH, potassium loading was found to exert a strong trophic action. The hypothesis is advanced that potassium loading requires the integrity of both the renin-angiotensin system and the hypothalamo-hypophyseal axis to exert its powerful direct stimulating effect on the growth and steroidogenic capacity of the rat zona glomerulosa.
Age- and sex-associated modification of plasma melatonin concentrations in man. Relationship to pathology, malignant or not, and autopsy findings
Authors: Touitou Y. , Fevre-Montange M. , Proust J. , Klinger E. , Nakache J. P.
Published: December 2008

Abstract. Plasma melatonin concentrations were determined in 757 unselected elderly patients aged 80.9 ± 9.7 years. The daytime (8–9.30 h) plasma levels of melatonin were in the so-called normal range in only one third of the population whereas 65% of the subjects had abnormal levels of the hormone, most often decreased i.e. less than 0.17 nmol/l (53%) and sometimes increased i.e. 0.43 nmol/l or higher (12%).

A control group of healthy elderly subjects showed the same distribution as the entire population. A sex-difference with significantly higher levels of plasma melatonin in elderly women was observed. With respect to pathology and autopsy findings high levels of the hormone correlated with cancer, chronic renal failure, cardiovascular disease, biological inflammatory syndrome and diabetes. Low levels correlated with neurologic disease, tobacco or alcohol addiction. However, some of these relations were found to be sex-related as they were observed in women but not in men. Our data indicate that pineal function seems to be often altered in elderly human subjects and suggest potential diagnostic applications of melatonin determination.
Changes of molecular forms of growth hormone in bromocriptine treated acromegaly in relation to changes of somatomedin-C and clinical response
Authors: Nortier J. W. R. , Croughs R. J. M. , Donker G. H. , thijssen J. H. H. , Schwarz F.
Published: December 2008

Abstract. Eleven patients with active acromegaly were treated with 10–20 mg bromocriptine daily for a period of 6–9 months. The clinical response was evaluated by a 'clinical and metabolic improvement score'. The biochemical response was evaluated by measurement of both the mean plasma growth hormone (GH) level during the day and the somatomedin-C (Sm-C) concentration.

Before and at the end of the treatment period plasma samples were fractionated by Sephadex G-100 chromatography in order to study the effects of chronic bromocriptine treatment on the concentrations of total GH and its different molecular forms.

The main observations may be summarized as follows:

Three immunoreactive components were observed on Sephadex chromatography corresponding to molecular weight above 100 000 (big-big GH), 40000–60000 (big GH) and 20000–22000 (little GH).

Bromocriptine treatment induced preferentially a reduction of little GH. There was a very good correlation between the decrease of little GH and total GH, and both were significantly correlated with the clinical response.

The correlation between the decrease of Sm-C values and that of little and total GH as well as between the decrease of Sm-C and the clinical response was poor.

It is concluded that a) measurement of little GH is not superior to the determination of total GH in the assessment of disease activity of bromocriptine treated acromegalic patients; b) both methods are superior to the measurement of plasma Sm-C levels; c) clinical response out of proportion ot the fall of total GH which can be explained by a preferential reduction of little GH, has not been observed in our investigations.
Differential effects of extracellular matrix on secretion of prolactin and growth hormone by rat pituitary tumour cells in vitro
Authors: Prysor-Jones R. A. , Silverlight J. J. , Jenkins J. S.
Published: December 2008

Abstract. Two types of rat pituitary tumour cells secreting both prolactin (Prl) and growth hormone (GH) were cultured in vitro either on plastic dishes or on surfaces coated with an extracellular matrix (ECM) derived from bovine corneal endothelium. The presence of ECM caused an increase in Prl but a decrease in GH. On one cell line the Prl response to thyrotrophin releasing hormone (TRH) was increased by ECM. There was an increase in the rate of spread of the cultures, an increase in cell protein, and DNA synthesis and a change in cell morphology when ECM was used. It is suggested that these observations can be explained by a sensitizing action of ECM to growth factors present in serum.
Effects of α-adrenoceptor agonists and antagonists on thyroid hormone secretion
Authors: Ahrén Bo
Published: December 2008

Abstract. The effects of various α-adrenoceptor agonists and antagonists on blood radioiodine levels were studied in mice pre-treated with 125I and thyroxine. The non-selective α-adrenoceptor agonist noradrenaline and the selective α1-adrenoceptor agonist phenylephrine both enhanced blood radioiodine levels. Noradrenaline was more potent than phenylephrine. Contrary, the selective α2-adrenoceptor agonist clonidine depressed basal levels of blood radioiodine. The non-selective α-adrenoceptor antagonist phentolamine and the selective α1-adrenoceptor antagonist prazosin both inhibited the noradrenaline-induced elevation of radioiodine levels, whereas the α2-adrenoceptor antagonist yohimbine had no such effect, except at a high dose level. All three α-adrenoceptor agonists, noradrenaline, phenylephrine and clonidine, inhibited the radioiodine response to TSH. In addition, TSH-induced increase in radioiodine levels was inhibited by prazosin, whereas yohimbine had no effect. Phentolamine inhibited the radioiodine response to TSH when given 2 h prior to TSH, whereas when given 15 min prior to TSH the response to TSH was potentiated by Phentolamine. It is concluded, that under in vivo conditions in the mouse, α1-adrenoceptor activation stimulates basal thyroid hormone secretion and inhibits TSH-induced thyroid hormone secretion. Further, α2-adrenoceptor activation inhibits basal thyroid hormone secretion. In addition, TSH-induced thyroid hormone secretion is inhibited by α1-adrenoceptor antagonism. Thus, α-adrenoceptors induce both stimulatory and inhibitory effects of thyroid function.
Long-term culture of differentiated human thyroid tissue
Authors: Mothersill Carmel , Seymour Colin , Moriarty M.J. , Cullen M.J.
Published: December 2008

Abstract. Human thyroid cells obtained during surgery have been maintained in monolayer culture for at least 2 months and without loss of morphological or functional differentiation. Samples as small as 0.5 g could be cultured but best results were obtained with samples of 5–10 g. The technique used was developed in this laboratory for sheep tissue and was applicable without significant modification to human tissue. It depends on the complete absence of media changes at any time during the culture period. Energy substrates are replenished by the addition of concentrated glucose solutions to the existing media at carefully monitored intervals.

Differences in both morphology and function could be observed between cultures derived from patients with different diseases, suggesting that the technique could have predictive value.
Forskolin stimulation of adenylate cyclase in human thyroid membranes
Authors: Kasai Kikuo , Suzuki Yoshinobu , Hiraiwa Masaki , Kuroda Hisamoto , Emoto Tatsushi , Nakamura Tsutomu , Shimoda Shin-Ichi
Published: December 2008

Abstract. Forskolin stimulates adenylate cyclase in human thyroid membranes approximately 7-fold with halfmaximal stimulation occurring at 5–10 μm. Guanine nucleotides are not required for stimulation of the enzyme by forskolin. Forskolin-stimulation is additive or greater than additive with that of TSH or Gpp(NH)p-(above 1 μm). Different from TSH- or Gpp(NH)p-stimulation of adenylate cyclase, uncoupling of the guanine nucleotide-binding regulatory component by increasing concentrations of MnCl2 did not result in uncoupling of forskolin stimulation. The finding indicates that forskolin may mainly act on the catalytic component of adenylate cyclase. From the present study, it is suggested that the diterpene forskolin stimulates adenylate cyclase in human thyroid membranes by a novel mechanism that differs from TSH- or Gpp(NH)p-stimulation, and that the diterpene may be a useful tool to investigate the metabolism of thyroid and its regulation in normal and pathological situations.
The importance of plasma free insulin and counterregulatory hormones for the recovery of blood glucose following hypoglycaemia in Type 1 diabetics
Authors: Madsbad Sten , Hilsted Jannik , Krarup Thure , Sestoft Leif , Christensen Niels Juel , Tronier Bente
Published: December 2008

Abstract. After induction of hypoglycaemia in 31 Type 1 (insulin-dependent) patients, the 10 patients with the slowest recovery of blood glucose from hypoglycaemia were arbitrarily compared with the 10 patients with the fastest recovery of blood glucose. No differences were found between the two groups regarding response of glucagon to hypoglycaemia, whereas the epinephrine (2-fold), norepinephrine (2.4-fold) and cortisol responses were significantly greater in the group with the slow recovery.

The plasma free insulin concentrations were higher (2-fold) in the group with slow recovery from 30 min after stop of insulin and throughout the study. This may be explained by a 3-fold greater amount of insulin binding antibodies in this group compared to the group with fast recovery from hypoglycaemia. An inverse significant correlation was demonstrated between the rates of recovery and the amounts of insulin binding antibodies in all the patients (P < 0.02).

This implicates that enhanced counterregulatory hormone responses in the group with the slow recovery from hypoglycaemia could not compensate for the hypoglycaemic effect of a concomitant higher plasma free insulin concentration. Insulin binding antibodies, acting as a depot of circulating insulin, may be a risk factor of prolonged hypoglycaemia in Type 1 diabetics.
Testosterone precursors in spermatic venous blood of normal men and varicocele patients
Authors: Andò S. , Giacchetto C. , Colpi G. M. , Beraldi E. , Panno M. L. , Sposato G.
Published: December 2008

Abstract. In the present study we determined progesterone (p), 17-OH-progesterone (17-OH-P), androstenedione (Δ4), dehydroepiandrosterone (DHEA) and testosterone (T) in spermatic venous blood of 34 varicocele patients and of 13 normal subjects. We also used the DHEA/Δ4 ratio as an index of the Δ5/Δ4 pathway ratio in testosterone biosynthesis.

The mean of T and Δ4 in the spermatic blood of varicocele (V) patients appeared to be significantly lower with respect to that of normal (N) subjects (T:N = 1718.2 ± 202.4 (sem) nmol/l, No. 11; V = 1243.7 ± 97 (sem) nmol/l, No. 34; P < 0.03. Δ4: N = 56.4 ± 5.6 (sem) nmol/l, No. 12; V = 38.1 ± 4 (sem) nmol/l, No. 27, 0.02> P>0.01).

A negative correlation was observed between the individual age of varicocele patients and 17-OH-P (No. 34, y = −30.66x + 1300, r = −0.57, P < 0.01) Δ4 values (No. 27, y = −1.981x + 96.52, r = −0.67, P< 0.01).

When the ratio of T precursors was evaluated, we observed a positive correlation between the P/17-OH-P ratio and age of varicocele (No. 33, y = 0.0065x–0.092, r = 0.45, P < 0.03). The 17-OH-P/Δ4 ratio was greatly increased with respect to that of normal subjects (N = 5.12 ± (sem), No. 12; V= 10.77 ± 1.31 (sem), No. 27; P<0.01).

These data suggest that the reduced T levels in spermatic venous blood of varicocele patients were due firstly to the enzymatic deficiency of 17-20-lyase and secondly to that of 17α-hydroxylase activity as the patients grow relatively older.

The negative correlation between the DHEA/Δ4 ratio and Δ4/T ratio was observed in normal subjects (No. 10, y = −0.00432x + 0.0542, r = −0.67, P < 0.03) as well as in varicocele patients (No. 27, y = −0.00399x + 0.0587, r = −0.48, 0.02 > P > 0.01). This indicates that in the testis of varicocele patients the testosterone remains prevalently supplied by the Δ5 pathway of biosynthesis.
Studies of the human testis. XIX
Authors: Waheed Abdul , Winters Stephen J. , Farrow George M. , Oshima Hiroyuki , Troen Philip
Published: December 2008

Abstract. Human testosterone-oestradiol-binding globulin (hTeBG) was purified from pregnancy serum by ammonium sulphate precipitation, preparative flatbed electrofocussing, Concanavalin A-Sepharose affinity chromatography, Sephadex G-150 gel filtration, DEAE-Sephadex chromatography and preparative polyacrylamide gel electrophoresis. The yield was 0.3 mg of hTeBG with a specific acitivity of 1.1 nmoles DHT bound per mg. An antiserum to TeBG was raised in rabbits. Anti-hTeBG IgG was separated from rabbit TeBG by DEAE-Affi-Gel-Blue chromatography. Anti-hTeBG was titrated using protein A-Sepharose which quantitatively binds IgG and therefore bound [3H]DHT-hTeBG-anti-TeBG complexes.

The androgen binding components from human testis were separated on Concanavalin A-Sepharose columns into excluded and retained fractions. The antibody bound both testis fractions with titration curves which paralleled that of TeBG, indicating that these androphilic proteins share common immunodeterminants with hTe-BG. The possibility that these testicular proteins are identical in amino acid sequence to TeBG and differ only in carbohydrate content will require further verification. Finally, these results indicate that antibodies to TeBG can be used to study human testicular androgen-binding protein.
Enhanced hypothalamic dopaminergic inhibition of LH, TSH and GH release in patients with pathological hyperprolactinaemia
Authors: Ho K. Y. , Smythe G. A. , Lazarus L.
Published: December 2008

Abstract. Recent studies have suggested that patients with prolactinomas have a defect in the central regulation of prolactin (Prl) release but it is not clear whether the defect results from a true loss of hypothalamic dopamine activity or from a functional inability of inherent dopaminergic inhibition to be mediated effectively. We have studied this question by the use of monoiodotyrosine (MIT, 1 g orally), a specific inhibitor of central dopamine synthesis to remove dopaminergic inhibitory control of Prl release in 10 normal ovulating women, 8 women on oral contraceptive steroids (OC) and 8 patients with pathological hyperprolactinaemia (PHP). LH, TSH and GH were also measured during the study in view of recent reports suggesting that dopaminergic mechanims may be involved in modulating their secretion. Subjects on OC had a significantly higher (P < 0.05) mean basal Prl (353 ± 34 vs 280 ± 26 mIU/l) and a significantly greater (P < 0.05) peak response (incremental change 2270 ± 300 mIU/l to MIT than normal controls (1320 ± 220 mIU/l). Patients with PHP had a highly significantly blunted (P < 0.001) Prl response (incremental change 290 ± 95 mIU/l) compared to controls. MIT administration caused a significant increase in LH (P < 0.05), TSH (P < 0.01) and GH (P < 0.01) in patients with PHP but not in normal or OC-treated subjects. The augmented Prl response of subjects on OC is consistent with an increase in dopaminergic inhibitory control of Prl release. The lack of Prl response in subjects with PHP is indicative of a functional loss of dopaminergic control. Whilst the levels of dopamine activity in normal controls and in subjects on OC are unimportant in regulating LH, TSH and GH release, the use of MIT has revealed a significant inhibitory effect of dopaminergic mechanisms in modulating the release of these hormones in patients with PHP. The response of these hormones in patients with PHP is consistent with a supraphysiological degree of hypothalamic dopamine activity. We conclude that the defect in the control of Prl release in patients with PHP results from an inability of dopaminergic inhibition to be mediated effectively.
Gonadotrophins and ovarian steroids in cattle II. Pulsatile changes of concentrations in the jugular vein throughout pregnancy
Authors: Schallenberger E. , Rampp J. , Walters D. L.
Published: December 2008

Abstract. Short-term secretion patterns (derived from samples collected from jugular vein cannulae every 20 min for 12 h) of LH, FSH, progesterone, oestradiol-17β, oestrone and prolactin were studied every 30 days during gestation in heifers. LH pulse frequency and amplitude was greater during the early (months 1-3) and end (months 8-9) than during mid-gestation when pulsatile LH secretion was almost abolished. The frequency of pulsatile FSH release, which was already twice as fast than of LH during early pregnancy, did not change throughout the whole gestation period. Mean, basal and maximal progesterone concentrations were highest during the first 3 months of gestation, were slightly reduced during mid-gestation and decreased further during the last 2 months preceding parturition. Pulses of progesterone occurred concomitantly with the parallel LH/FSH as well as the separate FSH pulses. Average oestradiol-17β concentrations during the first months of gestation were slightly higher than during the mid-luteal phase of the cycle and exceeded during mid-gestation concentrations measured at oestrus. Free oestrone could be detected as early as day 60 of pregnancy. Frequency and amplitude of short-term changes of oestrone increased after the 5th month. Discontinuous secretion of oestrone as well as oestradiol-17β was only arbitrarily but never consistently correlated with either each other or with pulsatile gonadotrophin release.

Apart form an occasional coincidence with pulsatile release of other hormones prolactin concentrations seemed to depend rather on the season of the year and time of the day than on the individual pregnancy stage.

It is concluded that pulsatile LH secretion is either abolished or greatly inhibitied during certain gestation periods (mid- and end-pregnancy) due to pronounced changes in hypothalamo-pituitary sensitivity against both ovarian and placental steroids while short-term secretion of FSH is not. Discontinuous release of ovarian progesterone may result out of pulsatile stimulation by FSH (in the presence of very infrequent pulsatile and low basal LH) whereas the discontinuous secretion of the placental steroids oestradiol-17β and oestrone is obviously independent of the short-term changes of both gonadotrophins.
Receptor-mediated glucocorticoid inhibition of cell proliferation in mouse growth cartilage in vitro
Authors: Silbermann Michael , Maor Gila
Published: December 2008

Abstract. The growth hormone of neonatal facial cartilage from ICR mice is inhibited by glucocorticoid treatment in vitro. A reduction of the overall tissue weight is accompanied by a substantial decrease in the protein content of the tissue. For the first 48 h in culture, hormone-treated cartilage undergoes a complete standstill in protein gain, and only thereafter the protein content increases, yet is markedly smaller than that of control specimens. Further, a significant reduction in the DNA content is seen already by 24 h, a feature that intensifies by 48 h. A slight recovery takes place thereafter. The reduction in DNA concentration is accompanied by a significant decrease in [3H]thymidine incorporation in acid-insoluble material. The inhibition of DNA synthesis by triamcinolone acetonide is protein- and RNA-synthesis-dependent. Autoradiographic examinations reveal that young cartilage cells are heavily labelled with [3H]dexamethasone and that this labelling is specific. To further substantiate the involvement of glucocorticoid-specific receptors in the latter's inhibitory effects, tissues were treated with cortexolone, this apparently 'masking' the cytosolic receptors for glucocorticoids, and thereby succeeded to eliminate the growth-inhibitory effect of triamcinolone. These results provide evidence for a receptor-mediated set of responses to glucocorticoids in these cartilage cells.
Differences in aetiology and thyroid function in endemic goitre between rural and urban areas of the Darfur region of the Sudan
Authors: Eltom M. , Salih M. A. M. , Boström H. , Dahlberg P.-A.
Published: December 2008

Abstract. To investigate further the possible causes of the difference in goitre frequency between the rural and urban areas of Darfur region in the Sudan, urinary iodine excretion (UIE) and thyroid hormone concentrations were measured in 97 goitrous and 31 non-goitrous subjects from rural Darfur, 62 goitrous subjects from urban Darfur and 37 non-goitrous subjects from Khartoum. The mean UIE was equally low in goitrous subjects from rural Darfur (56.2 ±43.1 μg/g creatinine) and urban Darfur (46.3 ± 20.7 μg/g creatinine) and both values were lower than that in the non-goitrous subjects from Khartoum (83.6 ±41.9 μg/g creatinine). Subjects from rural Darfur also had lower mean serum thyroxine and higher triiodothyronine and thyroid stimulating hormone levels. The mean serum thiocyanate level of 3.2 mg/l in goitrous subjects from rural Darfur was significantly higher than the values of 1.8 ng/ml in goitrous subjects from urban Darfur (P < 0.001) and 1.7 mg/l in non-goitrous subjects from Khartoum (P < 0.001). It is concluded that the additional contribution of goitrogenic factors in rural Darfur induces thyroid anomalies to a greater degree than are most likely caused by the iodine deficiency alone in subjects from urban Darfur.
Platelet and adipocyte thermogenesis in hypothyroid patients: a microcalorimetric study
Authors: Valdemarsson Stig , Fagher Birger , Hedner Pavo , Monti Mario , Nilsson-Ehle Peter
Published: December 2008

Abstract. Direct microcalorimetry was used for measurements of heat production in cell suspensions of platelets and adipocytes, obtained from hypothyroid patients before and after 3 months on full l-thyroxine substitution.

Platelet heat production was significantly lower than normal before treatment and increased in all 10 patients studied; the mean value increased from 51.3 ± 1.6 fW/cell before to 57.1 ± 1.8 fW/cell after therapy (P< 0.001).

Similarily, adipocyte heat production was initially significantly lower than normal and increased during treatment in all 6 patients investigated. The mean value for heat production per adipocyte was 18.8 ± 1.7 pW/cell before and 32.4 ± 2.5 pW/cell after therapy (P < 0.025), which is still below the level recorded in lean healthy subjects. The adipocyte size did not change significantly. The increase in adipocyte heat production was correlated to the increase in S-triiodothyronine levels (r = 0.84, P <0.05).

In hypothyroidism, the total metabolic activity seems to be comparatively more reduced in adipocytes than in platelets. A difference may exist between these cells with regard to recovery of normal metabolic acitivity during treatment for hypothyroidism. Direct microcalorimetry appears to be an adequate method for monitoring net metabolic effects of thyroid hormones in these cells.
Decreased plasma calcitonin response to a calcium clamp in primary hyperparathyroidism
Authors: Tørring O. , Bucht E. , Sjöberg H. E.
Published: December 2008

Abstract. In order preoperatively to evaluate the calcium induced plasma calcitonin (CT) response in patients with mild primary hyperparathyroidism (PHPT), 7 postmenopausal (PM) females with PHPT and 14 PM healthy subjects underwent a 2 h calcium infusion. The infusions were performed by means of the 'calcium clamp' technique previously described by us in order to obtain an identical calcium stimulus in all subjects. Immunoreactive calcitonin (iCT) was determined by means of a sensitive RIA utilizing rabbit antibodies directed against the carboxy-terminal amino acid sequence of the CT molecule.

All patients with PHPT had normal basal plasma iCT levels: 10 ± 5 pg-eq/ml (mean ± sd) as a group and not different from the control group: 13 ± 5 pg-eq/ml. In the control group significantly increased plasma iCT was seen at 30, 60, 90 and 120 min in contrast to that of the PHPT group where a blunted response was observed.

The results indicate a diminished CT reserve in these patients which may imply an impaired defence against the PTH mediated bone resorption seen in patients with PHPT.
Possible site of negative and positive feedback action of oestrogen on gonadotrophin secretion in normal women
Authors: Nagahara Yasuhito , Miyake Akira , Tasaka Keiichi , Kawamura Yasuhiro , Aono Toshihiro , Tanizawa Osamu
Published: December 2008

Abstract. For determination of the site of action of oestrogen (E) during the negative and positive feedback phases of gonadotrophin secretions, studies were made on the pituitary response to a small amount of LRH and the pulsatility of gonadotrophins after E administration in normal cycling women in the mid-follicular phase. The pituitary responses to an iv bolus of 2.5 μg of synthetic LRH were evaluated by measuring serum LH and FSH 2 h before and 8 h after administration of 20 mg of conjugated E (Premarin). In the next cycle, the pituitary responses to a same dose of LRH were also observed 2 h before and 56 h after E injection. The mean levels of serum LH and FSH and the peak responses to LRH were significantly (P < 0.05) decreased 8 h after E injection, but were significantly (P < 0.05) increased 56 h after E administration. In the third cycle, the pulsatility of gonadotrophins was evaluated by measuring serum LH and FSH every 15 min for 180 min before and 8 h and 56 h after E injection. The pulse frequencies of gonadotrophins were not significantly different before and 8 h and 56 h after E injection. The amplitudes of pulses 56 h after Premarin injection were significantly higher than those before the injection. These findings suggest that the negative and positive feedback effects of E on gonadotrophin secretion may be caused, in part, by its direct action on the pituitary response to LRH.
Bromocriptine therapy as pre-operative adjunct of non-functional pituitary macroadenomas
Authors: Zárate Arturo , Morán Carlos , Klériga Enrique , Loyo Mauro , González-Angulo Amador , Aquilar-Parada Eugenio
Published: December 2008

Abstract. Although bromocriptine administration produces reduction in size of prolactinomas, its effect upon non-functional pituitary adenomas is still uncertain. Nine patients with macroadenomas, 2 of them with prolactinomas and 7 with non-functional tumours, received bromocriptine prior to transsphenoidal surgery. Size reduction of tumour mass was assessed by computerized tomography and by visual field examination before and following bromocriptine treatment. There were no signs of size diminution or pathological changes in the nonfunctional adenomas treated pharmacologically during 15 to 360 days. Both patients with prolactinomas had radiological evidence of size reduction and morphological changes on microscopic examination. These 2 patients had tumours with prolactin granules (immunocytochemistry) and adenoma cells showed reduced cytoplasmatic, nuclear and nucleolar areas. Neither vascular damage, cell necrosis, nor infarction was observed by electron microscopy. Patients with non-functional tumours as determined by immunocytochemistry and hormone production did not benefit from bromocriptine. The suggestion that bromocriptine can be used as primary treatment for non-functional pituitary tumours is not supported by the present study. Conversely, in cases of macroprolactinoma, bromocriptine is a useful pre-operative adjunct when surgery is planned and for those patients in whom a surgical cure is considered difficult owing to the tumour size.
Urinary adenosine 3',5'-monophosphate (cAMP) response to antidiuretic hormone in diabetes insipidus (DI): comparison between congenital nephrogenic DI type 1 and 2, and vasopressin sensitive DI
Authors: Ohzeki Takehiko
Published: December 2008

Abstract. Urinary adenosine 3',5'-monophosphate (cAMP) excretion before and after administration of aqueous vasopressin (pitressin) and 1-deamino-8-d-arginine vasopressin (DDAVP) was measured in congenital nephrogenic and in vasopressin sensitive diabetes insipidus (VS-DI). Excretion of cAMP into the urine increased markedly in response to pitressin (676%) and to DDAVP (252%) in VS-DI. Nephrogenic diabetes insipidus (N-DI) could be divided into two categories (type 1 and type 2) in respect to urinary cAMP responsiveness. In type 1, cAMP excretion showed no definite change after stimulation with pitressin (102%) or DDAVP (127%). On the other hand, urinary excretion of cAMP was significantly elevated in response to DDAVP in familial cases of N-DI type 2 (1269%) without producing any concentrating effect on the urine. Two different defects are considered to be involved in the pathogenesis of N-DI.
Studies on the mechanism of acute inhibition of thyroglobulin hydrolysis by iodine
Authors: Bagchi Nandalal , Shivers Birdie , Brown Thomas R.
Published: December 2008

Abstract. Iodine in excess is known to acutely inhibit thyroidal secretion. In the present study we have characterized the time course of the iodine effect in vitro and investigated the underlying mechanisms. Labelled thyroid glands were cultured in vitro in medium containing mononitrotyrosine, an inhibitor of iodotyrosine deiodinase. The rate of hydrolysis of labelled thyroglobulin was measured as the proportion of labelled iodotyrosines and iodothyronines recovered at the end of culture and was used as an index of thyroidal secretion. Thyrotrophin (TSH) administered in vivo acutely stimulated the rate of thyroglobulin hydrolysis. Addition of Nal to the culture medium acutely inhibited both basal and TSH-stimulated thyroglobulin hydrolysis. The effect of iodide was demonstrable after 2 h, maximal after 6 h and was not reversible upon removal of iodide. Iodide abolished the dibutyryl cAMP induced stimulation of thyroglobulin hydrolysis. Iodide required organic binding of iodine for its effect but new protein or RNA synthesis was not necessary. The inhibitory effects of iodide and lysosomotrophic agents such as NH4C1 and chloroquin on thyroglobulin hydrolysis were additive suggesting different sites of action. Iodide added in vitro altered the distribution of label in prelabelled thyroglobulin in a way that suggested increased coupling in the thyroglobulin molecule. These data indicate that 1) the iodide effect occurs progressively over a 6 h period, 2) continued presence of iodide is not necessary once the inhibition is established, 3) iodide exerts its action primarily at a post cAMP, prelysosomal site and 4) the effect requires organic binding of iodine, but not new RNA or protein synthesis. Our data are consistent with the hypothesis that excess iodide acutely inhibits thyroglobulin hydrolysis by increasing the resistance of thyroglobulin to proteolytic degradation through increased iodination and coupling.