bluuebunny/crossref_metadata_2025 huggingface dataset:
Interaction between parathyroid hormone and prostaglandin E1 on cyclic AMP metabolism in rat kidney
Authors: Nagata Naokazu , Ono Yuriko , Kimura Narimichi
Published: December 2008

The interaction between parathyroid hormone (PTH) and prostaglandin E1 (PGE1) in influencing cyclic AMP metabolism in rat renal cortical tissue was examined. PTH and PGE1 stimulated additively the adenylate cyclase activity in the homogenate of the tissue. Both PTH and PGE1 enhanced the level of cyclic AMP in the incubated renal cortical tissue, but the effect of their simultaneous addition did not exceed the effect induced by PTH alone. Cyclic AMP accumulated in the incubation medium by stimulation by PTH was decreased by the simultaneous addition of PGE1. When the tissue was pre-incubated for 30 min with 2 to 10 μg/ml of PGE1, the magnitude of the increase of cyclic AMP caused by PTH subsequently added was lessened. However, the response to PTH of adenylate cyclase preparation obtained from the homogenate of PGE1-pre-treated tissue was not decreased. When first PTH was added to the incubating renal cortical tissue, the subsequent addition of PGE1 accelerated the decrease of cyclic AMP content in the tissue and decreased the amount of cyclic AMP released from the tissue. The interaction of PTH and PGE1 on cyclic AMP metabolism in the renal cortical tissue was in contrast to that seen in newborn rat calvaria where PGE1 and PTH acted additively in enhancing the level of cyclic AMP.
Hepatic metabolism of vitamin D3 in streptozotocin-induced diabetic rat
Authors: Sulimovici Sorel , Roginsky Martin S.
Published: December 2008

The effect of streptozotocin-induced diabetes on the in vitro conversion of vitamin D3 to 25-hydroxyvitamin D3 (25-OHD3) by isolated liver microsomes from rachitic rats was examined. Enzymic activity was significantly less than that observed in control animals (P< 0.001). Administration of insulin restored activity almost to control values. These findings provide evidence that diabetes in this animal model produces alterations in the metabolism of vitamin D.
Metabolism of a new synthetic progestagen, Org 2969, in female volunteers. The distribution and excretion of radioactivity after an oral dose of the labelled drug
Authors: Viinikka Lasse , Ylikorkala Olavi , Vihko Reijo , Hasenack Hans G. , Nieuwenhuyse Hugo
Published: December 2008

The metabolism of a new synthetic progestagen, Org 2969 was studied in 4 healthy female volunteers. During the first part of the study (Phase I), the volunteers ingested 50 μg (about 0.1 mCi) of [16-3H]Org 2969 together with 50 μg of ethinyloestradiol as a single dose. During the second part of the study (Phase II), a 10-day pre-treatment with the same dosage of nonradioactive compound preceded the administration of the radioactive steroid.

A peak level of total radioactivity, representing 3.16–5.02% of the dose given/l of serum, was achieved within 2–3 h in Phase I. During Phase II, the corresponding figures were 4.54–5.13% after 1.5–3 h. The difference was mainly due to an increase of freely-extractable steroids during Phase II. The difference can at least partly be explained by assuming a change in the kinetics of the metabolism of Org 2969 by pre-treatment with Org 2969 and ethinyloestradiol. The mean recovery of radioactivity in urine and faeces was 83.0%/48.1%/34.9% (total/urine/faeces) of the total dose in Phase I and 76.1%/45.2%/30.9% during Phase II. The differences in the total excretion and in the radioactivity excreted in the faeces were significant.
Plasma concentrations of levonorgestrel as a function of the release rate of levonorgestrel from medicated intra-uterine devices
Authors: Nilsson C. G. , Lähteenmäki P. , Robertson D. N. , Luukkainen T.
Published: December 2008

An effort was made to achieve different levels of plasma levonorgestrel (13-ethyl-17α-ethynyl-17-hydroxy-gon-4-en-3-one) (Ng) concentrations by the intra-uterine administration of levonorgestrel-releasing intra-uterine devices (IUD). Three different models were designed to release different doses of Ng daily. Sixteen women volunteered for the study and had a Ng IUD inserted post-menstrually. The effect of the IUDs on the ovulatory pattern was studied by measuring plasma concentration of oestradiol and progesterone by radioimmunoassay. Ng plasma concentrations were also measured by radioimmunoassay. In vitro experiments to measure the release of Ng from each type of device were carried out. Although some overlapping of mean plasma levels of Ng occurred during use of the three models of the IUDs, suppression of ovulation was clearly dosedependent. Wide variations in plasma levels of Ng were seen between individuals but quite uniform plasma levels were seen in each subject for up to one year3. IUDs where in vitro release rates were equivalent to each other also resulted in wide individual variations in plasma concentrations of Ng.
Prolactin secretion in man following acute and long-term cimetidine administration
Authors: Masala A. , Alagna S. , Faedda R. , Satta A. , Rovasio P. P.
Published: December 2008

In 20 patients with duodenal ulcer we measured serum prolactin levels following acute and long-term cimetidine administration. In addition, in 20 healthy volunteers we studied the effect of pre-treatment with bromocriptine, metergoline, nomifensine and cyproheptadine on cimetidine-induced prolactin release. Intravenous cimetidine stimulated prolactin secretion in patients and in normal subjects. In the latter, bromocriptine and metergoline pre-administration blunted the release of prolactin in response to iv cimetidine whereas nomifensine and cyproheptadine were ineffective. Long-term treatment with cimetidine (1.2 g daily for 3 months) had no effect on prolactin secretion in the 20 patients studied. No incidence of gynaecomastia, galactorrhoea or disorders of the menstual cycle was observed.
Variability in neurosecretory material and responses to reserpine of the pituitary neural lobe in five strains of rat
Authors: Edwards Brian A.
Published: December 2008

The levels of vasopressin and neurophysin in the neural lobe of the pituitary were measured in five strains of rat: Wistar, Sprague-Dawley, PVG, Chester Beatty and DA strains. The effect of reserpine administration (5 mg/kg body weight) was determined.

There were significant differences in the weight of the neural lobe and the vasopressin and neurophysin contents of this tissue in the various strains. It was possible to show that weight of the neural lobe was not necessarily related to hormone content.

The effects of reserpine also varied within the species for, while there was a fall in the vasopressin content in the Wistar and Chester Beatty strains, no change was observed in the Sprague-Dawley, PVG and DA strains.

The fall in the vasopressin level in the Wistar animals was not accompanied by a simultaneous fall in the vasopressin-neurophysin content.
Peripheral blood lymphocyte transformation in response to human thyroid fractions in patients with Graves' hyperthyroidism and ophthalmopathy
Authors: Wall J. R. , Trewin Anne , Joyner Diane M.
Published: December 2008

Peripheral blood lymphocyte (PBL) transformation in response to human thyroid fractions was carried out in patients with Graves' hyperthyroidism and ophthalmopathy. The fractions used were, an extract, a soluble (cytosol) fraction, and membranes prepared by differential centrifugation at (i) 6500 × g (mitochondria), (ii) 10000 × g (plasma membranes as used in the radioreceptor assay for thyroid stimulating antibody (TSAb) and (iii) 40000 × g (microsomes). Results were expressed as stimulation indices (SI). Mean SI for patients were significantly increased compared with those for normals for cytosol and mitochondria but not the other fractions. Taking the upper limit of normal as mean + 2 sd for normal subjects for each fraction, positive tests were found in 12 of 35 patients tested. This was in response to extract in 3 of 32 patients, to the soluble fraction in 10 of 31 patients, to mitochondria in 2 of 13 patients, to plasma membranes in 1 of 33 patients, and to microsomes in 1 of 27 patients. Positive tests were associated with hyperthyroidism but not ophthalmopathy.
Highly specific solid phase immunoextraction of TSH using anti-TSH antibodies purified by affinity chromatography
Authors: Ponsin Gabriel , Mornex René
Published: December 2008

Highly specific anti-TSH antibodies were purified from a crude antiserum preparation by affinity chromatography using TSH-sepharose column as the adsorbant. This procedure completely eliminated the original LH binding activities. The purified anti-TSH antibodies were then coupled to CNBr activated sepharose 4 B and used in separating TSH from rat pituitaries by batch procedure. This method is demonstrated to be highly specific for purifying labelled TSH from pituitaries previously incubated in the presence of [14C]tyrosine. The effect of TRH on TSH biosynthesis is presented as a biological application of this procedure.
T4 degradation rate and plasma levels of TSH and thyroid hormones in ten young bulls during feeding conditions and 48 h of starvation
Authors: Tveit Borghild , Almlid Torbjørn
Published: December 2008

The effect of starvation on thyroid hormones was studied during a starvation period of 48 h in 10 young bulls. Mean thyroxine degradation rate decreased from K/day 0.32 during feeding to 0.23 during fasting. Mean plasma concentration of T4 decreased to 75% of normal, and it was calculated that the mean thyroxine secretion rate during the starvation period was 24% of normal.

Plasma concentration of free thyroxine decreased to 54% of normal, indicating that the concentration of binding protein was not decreased.

T3 and reverse T3 decreased to about 60% of normal. This indicated a parallel decrease in the secretion of all 3 hormones. We did not find evidence of an inactivating pathway for T4 as has been shown in humans during starvation.

TSH decreased to 85% of normal.
T4, T3 and reverse T3 in the plasma of rats during the first 3 months of life
Authors: van der Heide D. , Ende-Visser M. P.
Published: December 2008

A very sensitive radioimmunoassay for reverse T3 in rat plasma is described. The concentrations of T4, T3 and reverse T3 in the plasma of male and female rats were determined during the first 3 months of life. T4 concentrations reached a maximum value of 5.2±0.7 μg/100 ml (mean ± sd) when the rats were about 16 days old. As of day 28 the average serum T4 was approximately 4 μg/100 ml. Concentrations of T3 reached a maximum value of 168±34 ng/100 ml (mean ± sd) during the 16–20 day period. A plateau value of about 40 ng/100 ml was maintained after about 70 days. For reverse T3 a maximum value of 17.1±4.2 ng/100 ml (mean±sd) was found in rats between 13 and 16 days old, followed by a steep decrease to 8.2±0.9 ng/100 ml around the 28th day and a subsequent continuous slow increase. For the T3/reverse T3 ratio (as a parameter of the direction of the conversion pathway) the highest value of 16 was found during the fourth week of life. After 70 days the T3/reverse T3 ratio was only 3.5. The reciprocal fluctuations between T3 and reverse T3, as found in man and sheep, are less pronounced in the rat. The very high metabolic clearance rate of reverse T3 compared to that of T3 could be the explanation.
The long-term effect of lowering dialysate magnesium on circulating parathyroid hormone in patients on regular haemodialysis therapy
Authors: Parsons V. , Papapoulos S. E. , Weston M.J. , Tomlinson S. , O'Riordan J. L. H.
Published: December 2008

Measurement of parathyroid hormone (PTH) in a group of patients on regular dialysis therapy (RDT) showed little acceleration of the development of raised concentrations until the dialysate concentration of magnesium was halved from 0.5 to 0.25 mmol/l. Patients with sustained concentrations of PTH changed less than those who were within the normal range at the outset.
Pancreatic hormonal release after glucose and arginine administration in anaesthetized pigs
Authors: Gustavsson S. , Johansson H. , Lundqvist G.
Published: December 2008

Somatostatin, pancreatic polypeptide (PP), insulin and glucagon were measured in pancreatic venous effluent and in mixed venous blood of anaesthetized pigs. After stimulation of insulin release with glucose and arginine, respectively, a prompt decrease in PP levels was found in pancreatic venous blood. Somatostatin declined after glucose administration but was unaffected by arginine. The changes in PP and somatostatin levels were not evident in systemic blood. The present results emphasize the advantage of selective sampling of pancreatic venous blood in studies on the possible interactions between pancreatic hormones. The marked decrease in PP seen after stimulation of insulin release in the present study, indicates that PP should be included together with somatostatin in further studies on pancreatic hormonal interplay.
Role of androgens in hCG-induced ovulation in PMSG-primed immature rats
Authors: Peluso J. J. , Stude D. , Steger R. W.
Published: December 2008

The effect of pre-treatment with the anti-androgens, cyproterone acetate (C.A.) and Flutamide (Fl) on hCG-induced ovulation in immature PMSG-primed rats was studied. The results showed that pre-treatment with either anti-androgen reduced the ovulation rate by 50%. Not all pre-ovulatory follicles (≥ 600 μm in diameter) in control and anti-androgen-treated rats ovulated in response to hCG. In control rats, hCG induced cumulus cell dispersement and resumption of meiosis in the ova of these non-ovulatory follicles; while C.A. or Fl treatment prevented these pre-ovulatory responses (P < 0.05). In a subsequent study, PMSG-primed rats were pre-treated with Fl and autopsied 8 h after hCG. In control rats, hCG reduced ovarian oestradiol content, did not alter ovarian testosterone content, increased ovarian progesterone content (P < 0.05) and increased the percentage of follicles with 3B-HSD activity within their granulosa cell layers (P < 0.05). Fl did not alter ovarian steroid content but blocked the hCG-induced appearance of 3B-HSD activity in the granulosa cells of pre-ovulatory follicles. This lack of 3B-HSD activity could result in a local decrease in progesterone within the non-ovulatory follicle. It appears that androgens, presumably synthesized in the theca interna play an important role in either ovulation or in maintaining responsiveness of the pre-ovulatory follicle to LH.
Somatostatin and the 24 h levels of serum TSH, T3, T4, and reverse T3 in normals, diabetics and patients treated for myxoedema
Authors: Weeke Jørgen , Christensen Stig Engkjær , Hansen Aage Prange , Laurberg Peter , Lundbæk Knud
Published: December 2008

The influence of somatostatin on serum TSH, 3,5,3′-triiodothyronine (T3), free T3, thyroxine (T4), free T4 and 3,3′,5′-triiodothyronine (reverse T3, rT3) was studied in 5 healthy young subjects, in 7 young patients with juvenile type diabetes on a fixed daily insulin dose, and in 5 patients with treated myxoedema. Blood samples were taken hourly during a 24 h control period and during a 24 h somatostatin infusion period.

Somatostatin infusion obliterated the night increase in serum TSH in all three groups. However, the lower daytime serum TSH was not altered by somatostatin. It has earlier been shown that somatostatin inhibits the TSH secretion induced by TRH. Taken together these findings suggest that the high TSH level at night is induced by a hypothalamic TRH surge, while the lower day level of TSH is quite independent of hypothalamic TRH.

Somatostatin infusion was accompanied by a minor fall in serum T4 in all groups. In normal subjects and diabetics serum free T3 fell 23 ± 6% and 25 ± 6%, respectively, during 24 h somatostatin infusion. In patients with treated myxoedema, serum free T3 was not significantly affected. These results are consistent with a decrease in thyroidal secretion during somatostatin infusion, as the cause for the fall in serum T3 in normal subjects and in patients with diabetes, while the monodeiodination of T4 to T3 in peripheral tissues is unaffected. However, an extrathyroidal effect of somatostatin on iodothyronine metabolism might also exist since serum rT3 increased 49 ± 19% in patients with treated myxoedema. In normal subjects and diabetic patients only a trend towards such a variation was observed.
Human thyroid stimulating activity and clinical state in antithyroid treatment of juvenile Graves' disease
Authors: Takata Ikuro , Suzuki Yukichi , Saida Kohki , Sato Tamotu
Published: December 2008

Human thyroid stimulating activity in 37 patients with juvenile hyperthyroidism was studied during the course of antithyroid drug treatment. Observation periods varied from 6 months to 6 years (average 3 years). The existence of human thyroid stimulator (HTS) in their sera was determined by triiodothyronine (T3) release from resected thyroid adenomas. A measurement of T3 above the control value of 140% was judged to be positive. Before treatment, 25 of the 28 patients with Graves' disease had HTS in their sera, one of the 7 patients with Hashimoto's thyroiditis had HTS, and none of the 19 normal children had HTS in their sera. During the therapy, 7 of 18 Graves' patients had HTS. After cessation of the therapy, 9 of 22 patients remained HTS-positive, and 8 of the 9 patients with positive HTS relapsed within 6 months, whereas in 13 HTS-negative patients, 3 escaped and 10 remained in remission. There was no significant correlation between human thyroid stimulating activity (HTSA) and the following: serum T3 concentration, 131I-thyroidal uptake, TSH responsiveness to TRH and antithyroid antibody titre. These results indicate that (1) almost all patients with Graves' disease have HTS when they are in a state of hyperthyroidism, (2) HTS tends to disappear with the clinicial remission, but its persistence seems to predict relapse in the future, and (3) routine laboratory tests cannot serve as alternative to HTS.
Binding of thyrotrophin to low molecular weight fragments of human thyroid membranes
Authors: Adlkofer Franz , Kotulla Peter , Schleusener Horst
Published: December 2008

The LATS absorbing activity from thyroid homogenates which is associated with the soluble thyroid fraction (4S-LAA) binds TSH in addition to LATS. This may indicate that 4S-LAA originates from the receptor sites for TSH at the thyroid cell surface. The affinity of 4S-LAA for TSH is much lower than that of thyroid membranes suggesting that 4S-LAA represents incomplete receptor sites or receptor sites which are altered in their structure.
Acceleration of puberty in boys with delayed puberty by clomiphene citrate. A clinical and laboratory study
Authors: Dickerman Zvi , Prager-Lewin Ruth , Lahmy Osnat , Laron Zvi
Published: December 2008

Clomiphene citrate was administered at a dose of 50 mg/day for 3 months to 29 boys with delayed puberty, 15 in a stage of early puberty (group 1) and 14 in stages of mid puberty (group 2). In both groups a significant acceleration in the advancement of pubertal signs was noted in the 6-month period following initiation of therapy as compared to a non-treated control group. A significant rise in the mean (± sd) basal plasma LH levels, from 1.0 ± 0.4 to 2.7 ± 2.2 mU/ml in group 1 (P < 0.05) and from 1.0 ± 0.6 to 2.2 ± 1.7 mU/ml in group 2 (P < 0.05) was observed following the treatment period with clomiphene. Concomitantly there was a rise of the mean basal plasma FSH level from 1.1 ± 0.4 to 2.0 ± 1.5 mU/ml in group 1 (P ± 0.05) and from 1.9 ± 1.6 to 3.4 ± 3.0 mU/ml in group 2 (P < 0.02). The mean LH peak response to an iv bolus of LRH (50 μg/m2 iv) rose from 8.3 ± 4.2 to 13.0 ± 5.3 mU/ml in group 1 (P < 0.05) and from 9.2 ± 5.8 to 12.6 ± 6.8 mU/ml in group 2 (NS). The mean peak plasma FSH response to LRH rose from 2.0 ± 0.6 to 5.9 ± 4.2 mU/ml in group 1 (P < 0.05) and from 4.3 ± 4.0 to 7.0 ± 6.8 mU/ml in group 2 (NS).

Clomiphene therapy caused a rise of the basal plasma testosterone level from 68 ± 53 to 313 ± 270 ng/100 ml in group 1 (P < 0.01) and from 103 ± 67 to 392 ± 248 ng/100 ml in group 2 (P < 0.01). The plasma testosterone response to one hCG stimulation (5000 U im), tested in 4 boys immediately before and after the 3-month period of clomiphene administration revealed an increase in both the basal and the peak testosterone levels (P < 0.05 and P < 0.001, respectively).

A standard clomiphene test consisting of the administration of 100–200 mg/day clomiphene citrate for 8 days was performed in 8 boys before initiation of clomiphene treatment for the 3-month period. In 4, including 2 boys in an early stage of puberty, there was a suppression of the basal level of gonadotrophins and their response to synthetic LRH. The other 4 boys, all of them in stages of mid-puberty, showed an increase in the basal and peak plasma gonadotrophin levels following LRH stimulation. In all 8 boys there was a significant rise of the basal plasma testosterone level. Despite the varying response to the short clomiphene test in these 8 boys, all gave a good response to the prolonged administration of clomiphene citrate. It was concluded that treatment with small doses of clomiphene citrate for a period of 3 months induces an acceleration of puberty in boys with delayed or slowlyprogressing puberty, once the stage of initiation of puberty has been passed.
Lithium and iodine combination therapy for thyrotoxicosis
Authors: Boehm Timothy M. , Burman Kenneth D. , Barnes Susan , Wartofsky Leonard
Published: December 2008

In order to compare the relative therapeutic efficacy of iodine (I) and lithium (Li) in thyrotoxicosis, investigate possible additive effects of these agents, and examine their effect upon thyroidal release, 17 thyrotoxic patients were assigned to groups given either I (n = 9) or Li (n = 8) alone during an initial treatment period, with the alternate drug added as combination treatment during a second treatment period. Half of the patients received methimazole (MMI). Three additional thyrotoxic patients received I during both treatment periods to evaluate the possibility of cumulative I effect upon thyroidal release during the second treatment period. A double isotope technique was utilized as an index of thyroidal release, employing 125I as an intra-thyroidal label and [131I] T4 as a marker of T4 disposal. During the first treatment period either I or Li induced comparable, significant (P < 0.05) decreases in thyroidal release, as measured by slopes of ratios of serum PB125I: PB131I and by percentage inhibition of fractional T4 release rate. In response to Li, there was a 55% decrease in the slope of PB125I: PB131I with MMI and a 52% decrease without MMI. In response to I, there was a 70% dercrease in the slope of PB125I: PB131I with MMI and a 57% decrease without MMI. Further significant (P < 0.05) decreases in the slopes of these ratios during the second, combined treatment period (I + Li) occurred only in those patients who had initially received I. No further decreases in the second treatment period were seen in patients receiving I during both treatment periods. Thus, I and Li together display additive inhibition of thyroidal release only if I is administered initially, but the combination, if Li is used first, does not appear to be more effective than Li alone.
Influence of corticotrophin on plasma testosterone in normal women
Authors: Vérine A. , Trouvé-Blanqui E. , Oliver C. , Boyer J.
Published: December 2008

The concentrations of ACTH and testosterone (T) in the plasma from 12 normal women (aged 18–35 years) were simultaneously determined at various times after im injection of 1 mg corticotrophin. The increase in the plasma level of total immunoreactive ACTH was maximal 0.5 h after the injection (mean value 1123 as compared to 36 pg/ml in the basal state); at 48 h, the ACTH level was still 2.4-fold that measured in the basal state. The administration of corticotrophin induced a broad increase in the mean level of plasma T which was highly significant (P < 0.001) at 4, 6, 8, 16 and 24 h after the injection. The maximum T response was detected at 16 h (mean value 477 as compared to 338 pg/ml in the basal state). The results indicate that plasma T is susceptible to stimulation by a pharmacological dose of ACTH in normal women. This effect should be taken into account in evaluating the indication of ACTH as a therapeutic agent.
Investigation of the secretion and metabolism of cortisol during a 100 km race using [4-14C] and [1 1α-3H] cortisol
Authors: Few J. D. , Thompson M. W.
Published: December 2008

A mixture of [11α-3H] and [4-14C]cortisol was administered orally to healthy men, following which urine was collected for 24 h. Four subjects acted as basal controls, going about their normal (sedentary) work; a further 3 resting subjects also received 100 mg cortisol orally (high cortisol controls) and 6 subjects competed in a 100 km race. Decreases in the carbon-14 specific activity of the cortisol metabolite excreted by the runners suggested that they seceted cortisol at 2–4 times the rate of the basal controls. This change was mirrored by the excretion of urine free cortisol but not by that of 17-hydroxycorticosteroids.

The isotope ratio (3H:14C) of 11-hydroxy metabolites of cortisol from the runners was intermediate between those of the basal and high cortisol controls, from which we conclude that though the fractional oxidation of cortisol to cortisone is reduced by increasing the cortisol pool, it is not affected by exercise per se. This and other results show that although continuous running for 6–8 h, involving energy expenditure in excess of 25 megajoules, leads to a moderate increase in the rate of cortisol secretion, running per se does not appear to markedly affect the metabolism of cortisol.
Effects of angiotensin I converting enzyme inhibitor (SQ 14225) on control of aldosterone
Authors: Eguchi Toyohisa , Saito Ikuo , Nakamura Ryuichi , Yasui Toshiyuki , Saruta Takao
Published: December 2008

To study effects of angiotensin I converting enzyme inhibitor (CEI), SQ 14225, on plasma aldosterone (PA), angiotensin I (AI), angiotensin II (AII), potassium and ACTH were administered with or without the simultaneous injection of SQ 14225 in rabbits. The direct effect of bradykinin on PA was also examined, since it is suspected to augment the action of kinin under the administration of CEI.

In rabbits the dose of 1 mg/kg of SQ 14225 by a bolus injection resulted in a marked elevation of plasma renin activity (PRA) and moderate but significant decreases in circulating AII and PA with only a little change of blood pressure. Decrements in circulating AII and those in PA observed after the injection of SQ 14225 were well correlated (r = 0.585, P < 0.05). Stimulatory effects of AII, potassium and ACTH on PA were not affected by SQ 14225, however, those of AI on PA and blood pressure were completely inhibited by pre-treatment of SQ 14225. The infusion of bradykinin showed a remarkable reduction in blood pressure and a small increment in PRA, circulating AII and PA.

These results may suggest that the inhibitory effect of acutely administered SQ 14225 on PA is mainly due to the inhibition of conversion from AI to AII, but not direct effects on adrenal glands. Furthermore, it was suggested that the augmented kinin is not related to the inhibitory effect of SQ 14225 on PA. In addition, the administration of SQ 14225 does not change the effects of potassium and ACTH on PA.
Radioimmunoassay of three oestrogens and three androgens in the same plasma sample after extraction and chromatographic separation
Authors: Paradisi Roberto , Lodi Sergio , Bolelli Gianfranco , Venturoli Stefano
Published: December 2008

The plasma levels of oestrone (Oe1), 17β-oestradiol (Oe2), oestriol (Oe3), testosterone (T), 5α-dihydrotestosterone (DHT) and androstenedione (A) were assayed by RIA in plasma obtained from peripheral venous blood. The hormones are isolated from the plasma extract, first by Sephadex LH-20 column chromatography (Oe2/Oe3/Oe1, T, DHT, A) and after Oe1, T, DHT, A by TLC on silica gel 60 F254. The accuracy, reproducibility and sensitivity of the method make it satisfactory for clinical studies.
Prevention of cystic ovary induction in rabbits by aminoglutethimide
Authors: Albrecht Eugene D.
Published: December 2008

Polycystic ovaries were induced in thyroidectomized rabbits by the administration of either 25 IU human chorionic gonadotrophin or 10 IU pregnant mare serum daily for a period of 20 days. Cystic ovaries in rabbits exhibited subnormal (P < 0.01) ovarian Δ5-3β-hydroxysteroid dehydrogenase (3β-HSD) concentration and specific activity. Since weight of cystic ovaries was markedly elevated, however, total capacity for Δ4-3-ketosteroid production was enhanced.

Concomitant administration of chorionic gonadotrophin and aminoglutethimide phosphate to thyroidectomized rabbits prevented the formation of cystic ovaries indicating that a steroid, or steroids formed beyond cholesterol in the biosynthesic pathway is necessary for the experimental induction of cystic ovaries in this laboratory animal.
Iodine induced thyrotoxicosis in apparently normal thyroid glands
Authors: Skare ståle , Frey Harald M. M.
Published: December 2008

Two male patients aged 36 and 52 years with thyrotoxicosis revealed a serum T3 of 2.8 and 6.5 nmol/l and a serum T4 of 166 and 238 nmol/l, respectively. Both had been exposed to iodine (2–10 mg daily) for 2–12 months before thyrotoxicosis was diagnosed. Urinary iodine excretion was high, 5000 and 10000 nmol/24 h (624–1250 μg). The uptake of 131I in the thyroid glands were low, none had goitre.

Their iodine intake was interrupted, urinary iodine excretion gradually decreased, and T3 and T4 in serum concomitantly normalized. They were clinically and biochemically euthyroid 9 and 11 weeks after withdrawal. After 14 and 22 weeks they had normal thyroid uptake of 131I, and thyroid scans showed glands of normal size and configuration, TRH-stimulation and a T3-suppression tests became normal. ESR was not elevated in any of the cases, thyroid antibodies against thyroglobulin and follicular cell microsomes were absent and TSAb was undetectable during the thyrotoxic stage.

Thus no evidence of any pre-existing and/or pre-disposing pathological condition in the thyroid glands were found. The mechanism for the iodine-induced thyrotoxicosis in such cases remains obscure.
Variations in serum T3, rT3, 3,3'-diiodothyronine and 3',5'-diiodothyronine induced by acute myocardial infarction and propranolol
Authors: Faber Jens , Kirkegaard Carsten , Lumholtz Ib Bo , Siersbæk-Nielsen Kaj , Friis Thorkild
Published: December 2008

Serum levels of thyroxine, 3,5,3'-triiodothyronine (T3), 3,3',5'-triiodothyronine (rT3), 3,3'-diiodothyronine (3,3'-T2), 3',5'-diiodothyronine (3',5'-T2) and TSH were measured in two clinical situations which are both known to induce a low serum T3 high serum rT3 syndrome: 1) during the early course of acute myocardial infarction (AMI) and after recovery, and 2) before and during one week's propranolol medication (20 mg 4 times a day). In 10 patients with AMI serum levels of the iodothyronines were unchanged on admission to hospital (in average 6.6 h after onset of symptoms). However, already 24 h after onset of symptoms serum T3 and 3,3'T2 were reduced whereas serum rT3 and 3',5'-T2 were increased. Serum T3 and 3,3'-T2 reached a nadir on day 4 and 3, respectively, whereas serum rT3 and 3',5'-T2 reached peak values 24 h after onset of symptoms.

In eight healthy, euthyroid volunteers propranolol medication induced similar changes in iodothyronine concentration as AMI did. However, the alterations were more delayed. Serum T3 decreased slowly reaching statistically significantly reduced values on day 7. Serum rT3 and 3',5'-T2 were significantly enhanced from day 3 and 4, respectively. A close parallelism in alterations of serum T3 and 3,3'-T2 levels was observed.

Our data suggest that T3 in the two situations studied is a major precursor for 3,3'-T2 probably as a consequence of reduced 5'-deiodinase activity. It seems possible that the mechanisms affecting the metabolism of the iodothyronines in AMI and during propranolol medication involved the same enzyme system. However, the late appearance of the alterations in serum iodothyronines levels during propranolol medication might indicate different modes of action.
Effect of receptor occupancy on [3H]dexamethasone binding to circulating leukocytes
Authors: Murakami Tohru , Brandon David D. , Loriaux D. Lynn , Lipsett Mortimer B.
Published: December 2008

To determine the effect of steroid occupancy of the glucocorticoid receptor on the measurement of total receptor concentration using Scatchard plot of [3H]dexamethasone (Dex) binding to circulating leukocytes, leukocytes were incubated with 10−7m cortisol or 10−9m Dex prior to [3H]Dex binding study. Total binding capacity calculated from Scatchard plot analysis of [3H]Dex binding was not significantly reduced after pre-incubation with cortisol. However, total binding capacity was significantly lower after pre-incubation with Dex. These data suggest that total glucocorticoid receptor concentration can be measured from a 3 h incubation of leukocytes obtained from untreated patients.
Oestrogens, compared to other steroids of testicular origin, in bloodplasma of boars
Authors: Claus R. , Hoffmann B.
Published: December 2008

Oestrogens, testosterone, and 5α-androstenone ('boar taint steroid') were determined in peripheral and spermatic vein blood plasma of boars. Oestrone was the predominant steroid in both the conjugated and the unconjugated fractions of total oestrogens. Concentrations of conjugated oestrogens in peripheral plasma generally are in the range of several nanograms/ml, which is similar to the range of 5α-androstenone and testosterone. Unconjugated total oestrogens are in the lower nanogram-range. These concentrations, however, are still higher than those during the oestrus in sows. Stimulation with hCG led to increased concentrations of peripheral plasma oestrogens, demonstrating their testicular origin. Comparative measurements in spermatic vein plasma and peripheral plasma show that in general the testis has to secrete different amounts of the individual steroid to maintain the appropriate peripheral level. A highly correlated course of all the steroids measured was apparent.

This was shown for the diurnal rhythm, the age-related changes and for the increase after application of hCG.
Calcium and phosphate metabolism in acromegaly
Authors: Halse Johan , Haugen Harry N.
Published: December 2008

A study of 28 consecutively admitted patients with active acromegaly revealed the following results with regards to calcium and phosphate metabolism.

When compared with controls, there was an increase in serum calcium levels corrected for total protein, urinary calcium was increased, but the tubular re-absorption of calcium was normal. There was a negative correlation between the urinary cAMP and calcium excretion indicating that hyperabsorption of calcium from the gut is the cause of the increased urinary calcium excretion.

Serum phosphate values were increased in acromegalics and correlated well with TmP/GFR which was also increased.

Immunoreactive parathyroid hormone (PTH) was increased in 5 patients, three of whom had hypercalcaemia. In the remaining patients the PTH values were scattered within the normal range. The urinary cAMP/creatinine ratio was increased in acromegalics, but most of this difference was abolished when urinary cAMP was expressed relative to 100ml of glomerulus filtrate.

It is concluded that parathyroid hyperactivity is a feature of acromegaly.
Clinical and pathological significance of sibling Graves' disease
Authors: Tanaka Toshio , Katayama Shoichi , Kuma Kanji , Tamai Hajime , Matsuzuka Fumio , Hidaka Hiroyoshi
Published: December 2008

The clinical picture and serum antithyroid antibodies in 16 pairs of siblings with Graves' disease were compared with an age and sex matched group of 32 patients with Graves' disease who did not have a family history of any thyroid disease (control patients). There was a significant difference in frequency and mean titres of antibodies to thyroglobulin between sibling patients. (positive 76.0%) and control patients (positive 40.0%), but not in microsomal antibodies (sibling; positive 92.0%, control; 92.0%). There were no significant differences in the mean values of 24 h 131I-thyroidal uptake, serum T3U, serum T4 and T3 concentrations before treatment between the two groups.

Lymphoid follicles and degeneration of the epithelia were more often found in the thyroid glands of sibling patients than in those of the control patients, when 32 (16 sibling, 16 control) thyroid glands from the same groups in the clinical study, including antibody series, were examined pathologically after subtotal thyroidectomy for Graves' disease. Moreover, there was a strong tendency to increased lymphocyte and plasma cell infiltration in the thyroid glands of sibling patients with Graves' disease.

The findings might indicate that Graves' disease is closely related to Hashimoto's thyroiditis, especially in sibling patients with Graves' disease.
Effects of chronic hypocalcaemia on plasma renin activity in man
Authors: Gedik O.
Published: December 2008

A study was carried out to investigate the role of serum calcium in the regulation of renin secretion. The subjects for this study comprised of two groups. Group 1 consisted of 10 patients with primary or secondary hypoparathyroidism. Blood samples for basal PRA (plasma renin activity) were drawn at 8 a.m. when the patients were recumbent and on a normal sodium intake. Then all the patients were given a constant diet containing 10 mEq sodium for 4 days and were given 80 mg of Furosemid orally every day. On the morning of the fifth day blood samples were drawn after the patients had been upright for 4 h. These patients were treated with vitamin D2 and when normocalcaemic states were achieved the same study was repeated. Group 2 (control group) consisted of 10 normal, healthy subjects of both sexes. They were prepared for the experiment in the same way as for group 1.

In the hypocalcaemic state mean serum calcium level was 5.6 ± 0.3 mg/100 ml. After treatment with vitamin D2, the mean serum calcium level was increased to 9.6 ± 0.1 mg/100 ml (P < 0.001). There was no significant difference in the mean serum sodium and potassium levels in either hypocalcaemia or normocalcaemia. But the mean stimulated PRA (12.12 ± 1.13 ng/ml/h) was found to be decreased in hypocalcaemia compared to in normocalcaemia and in the control group (22.87 ± 1.18 and 23.83 ± 0.86 ng/ml/h, respectively). The difference of means was significant (P < 0.001). There were no significant differences between basal PRA in hypocalcaemic and normocalcaemic state as well as in the control group. (P> 0.5, P > 0.2 and P> 0.5, respectively).

Our results indicate that serum calcium plays an important role in the regulation of renin secretion.
Stimulation of rat ovarian ornithine decarboxylase in vitro by hCG, amino acids and bovine serum albumin
Authors: Käpyaho Kirsti
Published: December 2008

Rat ovarian ornithine decarboxylase activity could be stimulated in vitro by a variety of factors, which apparently have different modes of action. Ovarian cells prepared from pre-pubertal rats by collagenase dispersion exhibited a low but detectable ornithine decarboxylase activity after a 6-h incubation in a defined medium. The enzyme activity was markedly enhanced in vitro by hCG, which also produced increased accumulation of cyclic AMP and stimulated the secretion of progesterone. In addition to the gonadotrophin, ovarian ornithine decarboxylase activity was strikingly stimulated by some non-essential amino acids, and especially by bovine serum albumin. While markedly enhancing ornithine decarboxylase activity, none of the latter additions increased the accumulation of cyclic AMP or enhanced the secretion of progesterone.

Bovine serum albumin enhanced powerfully ornithine decarboxylase activity in vitro at very small concentrations (from 0.75 μm). The half-life of the enzyme remained unchanged (26—28 min) upon stimulation indicating that the stimulation mechanism did not involve any stabilization of the enzyme.
Importance of time-related parameters of pre-optic electrical stimulation in the release of LH in the pentobarbital-blocked pro-oestrous rat
Authors: Johnson James H. , Somori Gabriel J.
Published: December 2008

The effectiveness of pre-optic stimulation in overcoming the pentobarbital blockade of ovulation in the rat has long been recognized and employed in neuroendocrine investigations. Although some reports have appeared comparing certain aspects of electrical stimulation in effectiveness in releasing LH, no complete study in female rats has been reported. The present study utilized regularly cycling rats of the Charles River CD strain in which ovulation was blocked by the injection of sodium pentobarbital on the afternoon of pro-oestrus. Electrical stimulation was delivered through bipolar platinum electrodes stereotaxically positioned in the pre-optic area, and LH was measured in plasma samples obtained at the onset of stimulation and 10, 20, 30, 45, 60, 80, 120 and 150 min thereafter. LH release was established in response to a baseline set of parameters: 15 Hz, 1.5 mA and 1.5 ms per phase, 30 s on/off for 60 min. Stimulations employing equi-coulombic increments of 1/3 introduced in each parameter in turn were compared in groups of 4—6 animals. Use of small increments in each parameter allowed the detection of those parameters to which the pre-optico-hypothalamo-pituitary system is most sensitive over the range studied, namely duration: of each pulse and of the overall stimulation period. This observation may be explained in terms of characteristics of the pituitary responsiveness.
Evaluation of LH, FSH, TSH, Prl, and GH secretion in patients suffering from prostatic neoplasms
Authors: Rolandi Ermanno , Pescatore Domenico , Milesi Giovanni M. , Giberti Claudio , Sannia Antonello , Barreca Tommaso
Published: December 2008

The concentration of luteinizing hormone (LH), of follicle stimulationg hormone (FSH), of thyroid stimulating hormone (TSH), of prolactin (Prl) and of growth hormone (GH) was evaluated, in basal conditions and during stimulation tests, in serum of 32 patients with benign prostatic hypertrophy (BPH), of 29 patients suffering from prostatic carcinoma and of a control group of similar age. Significant difference in pituitary Prl secretion was found between the prostatic patients and the control group.
'Proopiocortin fragments' in normal human adult pituitary. Distribution and ultrastructural characterization of immunoreactive cells
Authors: Celio Marco R. , Pasi A. , Bürgisser E. , Buetti G. , Höllt V. , Gramsch Ch.
Published: December 2008

The distribution and ultrastructure of cells immunoreactive towards antisera against synthetic fragments of proopiocortin were studied in human pituitaries by immunohistochemical methods. Anterior lobe cells exhibiting the ultrastructural characteristics of corticolipotropes, as well as all epithelial cells 'invading' the posterior lobe, display β-endorphin/β-lipotropin-ACTH immunoreactivities. At low dilution a β-lipotropin antiserum, raised with highly purified antigen, stains also somatotropes. α-MSH antibodies bind to certain corticolipotropic cells in the pars distalis and to only a few of the cells 'invading' the pars nervosa. Met-enkephalin antisera react only with isolated cells in the anterior lobe. These results indicate a striking difference in the processing of the proopiocortin precursor molecule in different corticolipotropic cells of the human hypophysis. Furthermore, the hypothesis of a homology between cells 'invading' the human neurohypophysis and those of the intermediate lobe of lower vertebrates, is questioned.
Discrepancy between the effects of desialylation of human chorionic gonadotrophin on in vitro ovarian biological activity and on receptor binding
Authors: Brand E. C. , Odink J. , van Hall E. V.
Published: December 2008

An in vitro bioassay based on progesterone production by enzymatically-dispersed immature rat ovary cells, was used to investigate the effect of sialidase treatment on the biological activity of human chorionic gonadotrophin (hCG). The potency in this bioassay system and in an ovarian receptor assay were compared, to substantiate possible discrepancies between the effect of this treatment on biological activity and on receptor binding.

Ovarian cells responded dose-dependently to the addition of hCG as well as sialidase treated hCG (asialo-hCG). Dose-response curves of hCG and asialo-hCG were parallel and the maximal stimulation levels reached were the same. Sub-maximal doses of hCG and asialo-hCG were additive. The potency of asialo-hCG was 65% of the original preparation. Addition of low concentrations of phosphodiesterase inhibitor resulted in a greatly enhanced sensitivity of the bioassay, but had no effect on the potencies of asialo-hCG and hCG.

In contrast to intact gonadotrophins, the receptor assay potency of asialo-hCG was more than three times the bioassay potency. In agreement with this, it was found that when equal amounts of 125I-labelled hCG and asialohCG were specifically bound to the ovarian cells, the latter stimulated progesterone production less effectively.

It is concluded that there is a discrepancy between the effect of desialylation on the biological activity and on the receptor-binding ability of hCG.
Cell-free synthesis of α and β subunits of human chorionic gonadotrophin with polyribosomes from early placenta
Authors: Maruo Takeshi , Koide S. S.
Published: December 2008

Polyribosomes were prepared from first trimester human placenta and assayed for protein synthetic activity in the cell-free translatory system derived from wheat germ or from first trimester placental tissue. High incorporation of [3H]proline was observed, whereas incorporation of [3H]glucosamine did not occur. The radiolabelled proteins synthesized by the wheat germ cell-free system were immunoprecipitated with specific antisera for hCG, α- and β-subunit and analyzed by electrophoresis on sodium dodecyl sulphate-polyacrylamide gels. The apparent molecular weight of the immunoprecipitable CG-α-protein was estimated to be 15 000 daltons, while that of the immunoprecipitable β-protein was about 24 000 daltons. Since the molecular weights of the polypeptide part of authentic α and β subunits are 10 200 and 16 000 daltons, respectively, the cell-free products may represent their precursor protein forms; pre-CG-α and pre-CG-β.

The rates of production of hCG, α and β proteins by in vitro incubation of placental polyribosomes with the wheat germ translating system were determined by the respective homologous radioimmunoassays. It is noteworthy that CG-β-protein production was highest during the initial 15 min of incubation and became limited subsequently, whereas an increase in hCG and α-protein formation was observed at 90 min of incubation. The present results suggest that the placental polyribosomes contain mRNA for α- and β-subunits. Earlier accelerated synthesis of CG-β protein might be required for the subsequent association with the newly synthesized α-subunit protein to form hCG.