bluuebunny/crossref_metadata_2025 huggingface dataset:
INTRAVENOUS AND PERORAL TRH STIMULATION IN SPORADIC ATOXIC GOITRE
Authors: Kirkegaard C. , Faber J. , Friis T. , Lauridsen U. Birk , Rogowski P. , Siersbœk-Nielsen K.
Published: December 2008

Thyrotrophin releasing hormone (TRH) stimulation test with 200 μg iv was performed in 35 patients with atoxic sporadic goitre. In 23 patients with diffuse goitre 7 showed a lack of increase in serum thyrotrophin (TSH) at a significantly increased frequency compared to controls (P = 0.0028). In 4 patients with solitary nodules 2 showed no significant response to TRH (negative), while 3 of the 8 patients with multinodular goitres had negative TRH test. Only 6 of the 12 TRH negative patients also had non-suppressible 131I uptake following T3. No significant difference in age and thyroid parameters was found between the TRH negative and TRH positive patients. In 7 TRH negative patients the test was repeated with 400 μg TRH but all remained negative. Five of these patients were given TRH perorally 80 mg daily for 2 weeks resulting in a significant increase in serum T4 and T3. No detectable increase in TSH was found. The response to iv bovine TSH in 4 TRH negative patients was found to be normal, suggesting that there was normal thyroid sensitivity to TSH. Our findings suggest that patients with TRH negative atoxic goitre can release biological active TSH following prolonged TRH stimulation. The high frequency of a negative standard TRH test in atoxic goitre seems to diminish the diagnostic value of the standard TRH test.
STIMULATION OF PERIPHERAL T3 FORMATION BY ORAL BUT NOT BY INTRAVENOUS GLUCOSE ADMINISTRATION IN FASTED SUBJECTS
Authors: Westgren U. , Ahrén B. , Burger A. , Melander A.
Published: December 2008

Fasting is known to promote a shift in the conversion of thyroxine (T4), more being deiodinated to an inactive form, reverse triiodothyronine (rT3), and less to active triiodothyronine (T3). The mechanism behind this change is not known, but it has recently been demonstrated that the proportion of dietary carbohydrates influences the serum concentration of T3 and rT3. Therefore, it is possible that the deiodination of T4 is subordinated to gastroenterohepatic regulation.

To explore this possibility, we administrated glucose by the oral or the intravenous route to volunteers, who had been fasted for 48 h. It was found that glucose normalized the low fasting T3 concentrations only after oral administration. This supports the assumption that some gastro-enterohepatic factor participates in the regulation of T3 formation.
THE EFFECT OF CALCIUM AND DIBUTYRYL-cAMP ON THE SECRETION OF PARATHYROID HORMONE BY HUMAN PARATHYROID ADENOMAS IN ORGAN CULTURE
Authors: Dietel M. , Dorn G. , Montz R. , Altenähr E.
Published: December 2008

The effect of different calcium concentrations as well as dibutyryl-cyclic adenosine 3′,5′-monophosphate (DB-cAMP) on the secretion of parathyroid hormone by human parathyroid adenomas taken from patients with primary hyperparathyroidism (pHPT) was studied in organ culture. Their influence on the release of hormone was determined. The tissue was incubated in culture medium for 4 h; the medium was changed hourly and analyzed for immunoreactive parathyroid hormone (PTH) by radioimmunoassay.

The hormone secretion showed an inverse relationship to different calcium concentrations in the medium and could be stimulated independently of the calcium concentration by adding DB-cAMP.

These results suggest that the examined parathyroid adenomas are sensitive to physiological stimuli.
CHARACTERIZATION OF HUMAN OVARIAN OESTRADIOL-17β OXIDOREDUCTASE ACTIVITY
Authors: Pittaway Donald E. , Andersen Richard N. , Givens James R.
Published: December 2008

Oestradiol-17β oxidoreductase activity, which catalyzes the interconversion of oestrone and oestradiol, was investigated in preparations of human ovaries. The enzyme activities were localized primarily in the 105 000 × g supernatant fraction; dialyzed supernatant preparations were used in subsequent studies. The pH optima were 6.9 for reduction and 8.1 for 17β-dehydrogenation. The apparent Michaelis constants for oestrone and oestradiol were 1 × 10-7 m and 5 × 10-7 m, respectively. The enzyme activity was present with either NADP(H) or NAD(H), though NADP(H) were the preferred cofactors. Non-aromatic steroids androstenedione, dehydroepiandrosterone, testosterone and 5-androstene-3β,17β-diol were poor substrates for the enzyme preparation. Methylation of the phenolic hydroxyl of oestrone and oestradiol resulted in slightly enhanced activities. The sulfhydryl reagent, N-ethylmaleimide, inhibited the reduction of oestrone. A dialyzed supernatant preparation retained approximately 79 % of the original enzyme activity when stored at −20°C for 6 weeks.
THE STIMULATION OF PROLACTIN SECRETION BY SULPIRIDE IN "ADOLESCENT GYNAECOMASTIA"
Authors: D'Agata R. , Andó S. , Gulizia S. , Condorelli L. , Paci C. , Scapagnini U. , Polosa P.
Published: December 2008

In order to evaluate the function of the hypothalamic-pituitary-prolactin axis in "adolescent gynaecomastia" (AG), sulpiride was administered to 7 normal boys and 7 boys with AG. The maximum increase in serum prolactin (PRL) above the mean baseline level (Δmax) was used as index of response. The sulpiride induced a greater PRL release in boys with gynaecomastia than in the controls.

Our data indicate that boys with gynaecomastia may have a greater pituitary prolactin pool. The results also illustrate the usefulness of specific neurotrophic agents such as sulpiride as important tools for evaluating the function of the hypothalamic-pituitary-PRL axis.
HIGH MOLECULAR THYROTROPHIN ("BIG"-TSH) FROM HUMAN PITUITARIES: PREPARATION AND PARTIAL CHARACTERIZATION
Authors: Erhardt Friedrich W. , Scriba Peter C.
Published: December 2008

Homogenates of human pituitaries were centrifuged at 30 000 × g and the supernatant chromatographed on Sephadex G-100. Approximately 1 % of the radioimmunologically measured total activity of TSH was eluted in the void volume. Rechromatography of this material on Sephadex G-200 usually showed TSH-activity at Kav = 0.5 (regular TSH), Kav = 0 (void volume-TSH) and at Kav = 0.3 ("big"-TSH). "Big"-TSH was extracted from the corresponding fractions by affinity-chromatography with solid phase anti-TSH. It was eluted with 5 mol/l ammonium thiocyanate and further characterized:

1. The molecular weight was approximately 200 000 by comparison with bovine catalase on Sephadex G-200.

2. Immunoidentity as compared with standard-TSH (M. R. C. 68/38) was shown by parallel dilution curves in the radioimmunoassay.

3. Concanavalin-A-Sepharose adsorbed "big"-TSH, which could be eluted with α-methyl-D-mannoside, indicating the glycoprotein nature of "big"-TSH.

4. On polyacrylamide-gel-electrophoresis pH 7.5, "big"-TSH migrated faster (RF = 0.32) than regular TSH (RF = 0.1), indicating a more negatively charged molecule.

5. "Big"-TSH, in contrast to regular TSH, was remarkably stable against 6 mol/l guanidine hydrochloride, suggesting a covalently linked (aggregate) structure.

6. 1 % mercaptoethanol destroyed the immunological activity of both regular and "big"-TSH.

7. "Big"-TSH was digested by trypsin, under mild conditions, to radioimmunologically active products with molecular weights between "big"- and regular TSH, but practically no regular TSH was formed.

8. "Big"-TSH and guanidine-treated "big"-TSH, as well as regular TSH and TSH from the void volume of Sephadex G-200 columns, exhibited biological activity in a cytochemical bioassay in good agreement with the respective immunological activities.
THE EFFECT OF LUTEINIZING HORMONE-RELEASING HORMONE AND STEROIDS ON THE RELEASE OF LH AND FSH FROM INCUBATED TURKEY PITUITARY CELLS
Authors: Godden Patricia M. M. , Luck M. R. , Scanes C. G.
Published: December 2008

The secretion of immunoreactive luteinizing hormone (IR-LH) and follicle stimulating hormone (IR-FSH) by turkey pituitary cell suspensions has been investigated. No significant effects of synthetic ovine luteinizing hormone-releasing hormone (LH-RH) on gonadotrophin release were found with cells from 17 to 19 week old birds, though IR-LH secretion was elevated with tissue from young (13 weeks) birds. Although IR-FSH secretion was increased in the presence of progesterone alone, effects of oestradiol and testosterone on IR-FSH release and of oestradiol, progesterone and testosterone on LH-RH release were observed when the steroid treatment was combined with that of LH-RH.
HOMOLOGOUS RADIOIMMUNOASSAY FOR CANINE PROLACTIN
Authors: Knight P. J. , Hamilton J. M. , Scanes C. G.
Published: December 2008

A homologous double antibody radioimmunoassay has been developed for canine prolactin. Purified canine prolactin was iodinated by lactoperoxidase/H2O2 to an average of 101 ± 10.1 μCi/μg. Antiserum was used at a final dilution of 1:80 000 and at this concentration bound approximately 20% of the added tracer in the absence of competing unlabelled prolactin. Partial cross-reaction was observed with ovine and bovine prolactin but there was no cross-reaction with a highly purified canine growth hormone preparation. Dilutions of pregnant and lactating bitch sera were parallel to the purified canine prolactin standard curve. Mean prolactin levels in normal male and anoestrous females were 8.8 ± 0.8 and 12.6 ± 2.6 ng/ml, respectively. Thyrotrophin-releasing hormone (TRH) induced a consistent elevation in prolactin levels 15–30 min after intravenous injection.
EFFECT OF PROLONGED ORAL ADMINISTRATION OF TRH ON PLASMA LEVELS OF THYROTROPHIN AND PROLACTIN IN NORMAL INDIVIDUALS AND IN PATIENTS WITH PRIMARY HYPOTHYROIDISM
Authors: Frey Harald M. M. , Haug Egil
Published: December 2008

Forty mg TRH/day was given orally for 3 weeks to 10 euthyroid women and 10 women with primary hypothyroidism on low replacement doses of thyroxine. Once weekly oral TRH was replaced by an iv TRH-test (0.4 mg) with measurement of serum concentration of TSH, prolactin (PRL), thyroxine (T4), triiodothyronine (T3) and cholesterol.

In the normal group, mean serum T4 concentration increased after one week and remained elevated. Serum TSH concentration showed a slight tendency to decline. Maximal rise in TSH concentration after iv TRH (ΔTSH) fell from a mean of 4.0 ng/ml to 1.4 ng/ml within one week and stayed low. T3, cholesterol, PRL and ΔPRL were normal and unchanged throughout.

In the hypothyroid group T4, T3, cholesterol, PRL and ΔPRL were not influenced by the TRH administration. In 2 patients (with the highest serum T4 concentrations) serum TSH concentration was normal and resistant to iv TRH. Of the 8 patients with elevated TSH, basal level and ΔTSH did not change in 2 (with subnormal T4 levels and the highest TSH levels). In the other 6 (with intermediate T4 levels) basal TSH fell from a mean of 10.1 ng/ml to 4.2 ng/ml, and ΔTSH from 10.0 ng/ml to 3.3 ng/ml after three weeks.

It is concluded that in addition to feed-back effect of thyroid hormones, the pituitary response to long-term administration of TRH is determined by other factors. Among these may be reduced pituitary TRH receptor capacity and the activity of the TSH producing cells.
TOTAL AND "ACTIVATED" PERIPHERAL BLOOD T LYMPHOCYTES IN PATIENTS WITH THYROID DISORDERS
Authors: Wall J. R. , Gray B. , Greenwood D. M.
Published: December 2008

The percentage of total and "activated" peripheral blood T lymphocytes was measured in patients with (i) hyperthyroid Graves' disease selected for absence of ophthalmopathy, (ii) treated Graves' disease, with ophthalmopathy, and (iii) other thyroid disorders including subacute thyroiditis, using sheep red blood cell rosette tests. No patient had significantly increased levels of either total or "activated" T lymphocytes. On the other hand, the percentage of total T cells was below normal in 8 of 18 patients with hyperthyroid Graves' disease and in 6 of 18 patients with ophthalmopathy compared with only one of 12 patients with nodular goitres. Similarly, low levels of "activated" T cells were demonstrated in 5 of 18 patients with hyperthyroid Graves' disease and in 10 of 18 patients with ophthalmopathy compared with only one of 12 patients with nodular goitres. Three of four patients with subacute thyroiditis tested had depressed levels of total T lymphocytes whilst only one had low levels of "activated" T lymphocytes. Levels returned to normal during the recovery phase in the two patients with positive tests who were retested. Depressed levels of T lymphocyte populations in patients with Graves' disease and subacute thyroiditis may be due to feedback suppression and/or "exhaustion" in association with the thyroidal and orbital immunological reactions.
DISTRIBUTION OF LATS ACTIVITY IN IMMUNOGLOBULIN G SUBCLASS
Authors: Ochi Yukio , Yoshimura Manabu , Hachiya Takashi , Miyazaki Tadayoshi
Published: December 2008

The immunological character of LATS was examined by affinity chromatography on Anti-IgG, Anti-Fab, Anti-Fc and Staphylococcal Protein A bound Sepharose. By affinity chromatography on Anti-IgG, Anti-Fab and Anti-Fc bound Sepharose, it is possible to separate LATS-immunoglobulin from LATS positive serum without loss of activity.

Affinity chromatography on Protein A bound Sepharose is useful for obtaining further purified LATS-immunoglobulin. By this method, it is possible to separate IgG molecules of the subclasses IgG(1), IgG(2) and IgG (4) with high LATS activity. LATS activity was not found in the IgG(3) fraction.

When IgG(1) fraction was purified from the fraction containing the 3 subclasses of IgG(1), IgG(2) and IgG(4), about 85 % of total protein was found in IgG(1). However, specific activity per protein of LATS in IgG(1) fraction did not change remarkably.

After papain hydrolysis the thyroid stimulating activity of LATS-immunoglobulin was located in Fab fraction of these 3 subclasses of IgG(1), IgG(2) and IgG(4), and especially in IgG(1). The Fab fraction presents a short acting type of thyroid stimulating activity. These data indicate that LATS activity is mainly distributed in the Fab fragment of IgG(1).
RESPONSES OF SERUM GONADOTROPHINS TO LH-RELEASING HORMONE AND OESTROGENS IN JAPANESE WOMEN WITH POLYCYSTIC OVARIES
Authors: Aono Toshihiro , Miyazaki Masatoshi , Miyake Akira , Kinugasa Takayuki , Kurachi Keiichi , Matsumoto Keishi
Published: December 2008

In order to define the abnormality in gonadotrophin secretion in Japanese women with polycystic ovaries (PCO) who rarely show virilization and markedly enlarged ovaries, basal levels of LH and FSH, and responses of serum gonadotrophins to LH-releasing hormone (LH-RH) or oestrogens were determined by radioimmunoassay. Eleven patients with PCO diagnosed by laparotomy or laparoscopy and 30 normal women in the follicular phase were studied.

The mean (± sd) basal level of LH was significantly higher in patients with PCO than in normal controls (PCO 28.6 ± 2.4 vs. normal 10.9 ± 3.0 mIU/ml), while the mean FSH level in PCO patients was not significantly different from that in the normal controls (9.7 ± 0.7 vs. 11.4 ± 2.6 mIU/ml). The mean LH/FSH ratio in PCO patients was significantly higher than that in normal controls (3.2 ± 0.9 vs. 1.0 ± 0.3). Exaggerated response of LH to LH-RH was observed in PCO patients, while the FSH response was comparable with the normal controls. Ten out of 11 patients with PCO showed LH release exceeding the basal level after bolus iv injection of 20 mg conjugated oestrogens (Premarin®), and virtually the same mean net increase in LH from the basal level was obtained in both PCO patients and normal controls.

Since the abnormalities in gonadotrophin secretion in Japanese women with PCO are not different from those reported in patients with PCO in Europe and USA, it seems likely that lower incidence of markedly enlarged ovaries and virilization in Japanese patients may be caused by the difference in ovarian response to gonadotrophin.
THE EFFECT OF LUTEINIZING HORMONE-RELEASING HORMONE IN HYPOGONADOTROPHIC EUNUCHOIDISM
Authors: Bremner William J. , Fernando Nihal N. , Paulsen C. Alvin
Published: December 2008

Fourteen patients with hypogonadotrophic eunuchoidism (HE), 10 males and 4 females, received luteinizing hormone-releasing hormone (LH-RH) as 4-h intravenous infusions of 0.2 μg/min or as subcutaneous (sc) injections of 200 μg. Repeated LH-RH administration over 4 days (200 μg sc daily) was undertaken in 8 patients. Eight of the 10 males and all 4 of the females were found to have definite elevations of luteinizing hormone (LH) and follicle stimulating hormone (FSH) following their first exposure to exogenous LH-RH. The patients included 2 males and 1 female with variant forms of HE, all of whom showed responses of both gonadotrophins.

When the first exposure of HE patients to exogenous LH-RH was as a 4-h infusion, the biphasic pattern of LH increase characteristic of normal adults was not found. Instead, a monophasic and qualitatively small LH increase occurred, similar to that found in pre-pubertal children and in anorexia nervosa. In 2 patients with an initially abnormal LH response, a 4-h LH-RH infusion following 4 days of LH-RH injections (200 μg sc/day) produced a normal biphasic LH increase. These results imply that maintenance of the two pools of pituitary LH demonstrable in normal adults depends on adequate production of endogenous LH-RH.

Increases in FSH following the initial exposure to LH-RH were generally as great or greater than those of normal adults in spite of the fact that LH responses tended to be smaller than those of adults. Four days of LH-RH administration (200 sc daily) did not lead to consistent increases in gonadotrophin responsiveness. Increases of testosterone or oestradiol production could not be demonstrated, even with 4 to 5 days of LH-RH administration. Exogenous sex hormone therapy markedly inhibited gonadotrophin responsiveness to LH-RH.
THE EFFECT OF STRESSFUL DIAGNOSTIC STUDIES AND SURGERY ON ANTERIOR PITUITARY HORMONE RELEASE IN MAN
Authors: Sowers J. R. , Raj R. P. , Hershman J. M. , Carlson H. E. , McCallum R. W.
Published: December 2008

The hormonal response of the anterior pituitary was studied in 10 normal males undergoing treadmill exercise testing, in 5 male patients undergoing diagnostic gastroscopy, and in 8 male patients undergoing elective surgery under general anaesthesia. Serum TSH was depressed below the baseline value at 2 and 3 h post-treadmill exercise, at 1, 2 and 3 h post-gastroscopy and from 10 min through 2 h post-surgery. Serum triiodothyronine was depressed below the baseline value at 10 min through 2 h post-surgery. Serum prolactin, growth hormone and cortisol were elevated by all three stressful procedures. Both gastroscopy and surgery resulted in an elevation of serum luteinizing hormone levels. There was no significant change in serum FSH levels in any of the three procedures. The post-stress depression in TSH levels could result from the suppressive effect at the hypothalamic-pituitary level of high serum levels of cortisol generated by the stress of the procedures.
STUDIES ON CIRCADIAN VARIATIONS OF PLASMA TSH, THYROXINE AND TRIIODOTHYRONINE IN MAN
Authors: Lucke C. , Hehrmann R. , von Mayersbach K. , von zur Mühlen A.
Published: December 2008

To evaluate the existence of circadian variations in thyroid hormone and TSH levels, blood was drawn every 20 min for 24 h in four and for 14 h in one volunteer. Hormones were measured by sensitive radioimmunoassays.

TSH:

A diurnal rhythmicity could be demonstrated with peaks from 8 p. m. to 2 a. m. and a nadir from 7 a. m. to 2 p. m. Superimposed on the diurnal rhythm multiple shortlived fluctuations were observed.

Thyroxine:

Pooled data showed peak values from 8 a. m. to 12 a. m. and lowest levels from 11 p.m. to 3 a.m. Again, shortlived fluctuations were superimposed on the diurnal rhythm in all instances.

Triiodothyronine:

Hormone levels were highest from 7 a. m. to 1 p. m. and lowest from 11 p. m. to 3 a. m. Fluctuations in T3 levels were less marked than those of T4.

Diurnal variations in hormone levels can be demonstrated in most, but not in all instances. Fluctuations are minor and do not exceed the normal range. Therefore these changes are of no relevance in routine testing of these hormones.
EARLY EFFECTS OF THYROID STIMULATING HORMONE (TSH) ON EXOCYTOSIS AND ENDOCYTOSIS IN THE THYROID
Authors: Ericson Lars E. , Johansson Bengt R.
Published: December 2008

The early effect (3 min) of thyroid stimulating hormone (TSH) on exocytosis-endocytosis in the rat thyroid follicle cell was investigated by electron microscopic morphometry. All rats used were pre-treated with thyroxine for 2 days prior to the experiments. In control rats, the membrane surface area of exocytotic vesicles, the only type of vesicle present in the apical part of the follicle cell, approximately equaled that of the apical plasma membrane. Intravenous administration of TSH caused a significant decrease in the membrane surface area of exocytotic vesicles by about 20 % and a corresponding, significant increase in the membrane surface area of the apical plasma membrane by about 20 %. Pseudopods were present in 4 of 6 TSH-injected rats examined, but the membrane surface area of these structures was only 15 % of the increase in the surface area of the apical plasma membrane. The total membrane surface area analyzed was not influenced by injection of TSH.

We conclude that the initial effect of TSH on the thyroid follicle cell is a re-distribution of membrane from exocytotic vesicles to the apical plasma membrane. This conclusion is in harmony with our previous observations which indicate that the (membrane-requiring) endocytotic response after TSH is regulated by the amount of membrane material added to the apical plasma membrane by exocytosis.
EVALUATION OF A THERAPEUTIC REGIMEN IN CUSHING'S DISEASE
Authors: Lamberts S. W. J. , de Jong F. H. , Birkenhäger J. C.
Published: December 2008

Eighteen unselected patients with Cushing's disease were treated by unilateral adrenalectomy followed by conventional external pituitary irradiation (4500 rads). In 9 of these patients (50 %) a remission has been reached as judged by the clinical picture and the cortisol secretion rate (CSR) up to an average of 5 years after operation (follow-up varying between 1 and 7.5 years). The 9 other patients showed a relapse making necessary a second adrenalectomy after an average of 15 months (5 to 57 months). Four of these patients had a slightly enlarged (two cases) or asymmetrical sella turcica (two cases).

The gain of this therapeutic regimen was that no permanent adrenal insufficiency is induced in 50 % of the patients, that no pituitary tumours developed and that no loss of pituitary function occurred. Before treatment the group of 9 patients, who did not improve or relapsed after treatment, showed a greater rise of plasma cortisol in response to lysine vasopressin, a (greater) decrease of plasma cortisol in response to a single oral dose of 1 mg dexamethasone and an earlier decrease of the urinary 17-OGS in response to 2 mg dexamethasone four times daily orally. It is concluded that in the patients whose hypothalamo-pituitary-adrenal axis could be manipulated less this therapeutic regimen had a better result.
QUANTIFICATION OF ANDROGEN BINDING, ANDROGEN TISSUE LEVELS, AND SEX HORMONE-BINDING GLOBULIN IN PROSTATE, MUSCLE AND PLASMA OF PATIENTS WITH BENIGN PROSTATIC HYPERTROPHY
Authors: Krieg M. , Bartsch W. , Herzer S. , Becker H. , Voigt K. D.
Published: December 2008

The in vitro binding of 5α-dihydrotestosterone (5α-DHT) in benign prostatic hypertrophy (BPH), rectus abdominis muscle and plasma of 14 patients was characterized and quantified by agargel electrophoresis. The respective endogenous tissue and plasma levels of 5α-DHT and testosterone (T) were determined by radioimmunoassay, and the plasmatic sex hormone-binding globulin (SHBG) concentration was estimated in the 14 patients by an (NH4)2SO4 precipitation technique. Finally the in vitro conversion of 5α-DHT to the 5α-androstanediols in the BPH at 0°C after a 20–24 h incubation period was analyzed by thin-layer chromatography.

The main results were as follows: (1) In 12 out of 14 BPH cytosols three charcoal resistant binding peaks were found, of which peak 1 represents SHBG, peak 2 the specific receptor protein and peak 3 a binding protein with relatively high binding capacity and low affinity for 5α-DHT. In two cases peak 2 was absent. In 11 out of 14 muscle cytosols three binding peaks are also present, resembling those of the BPH. (2) The receptor peak is reduced on average 38 % by unlabelled 5α-DHT, 23 % by cyproterone acetate (CYAC) and 29 % by oestradiol. The parallel data for the SHBG peak are: 62% by 5α-DHT, 22% by CYAC and 49% by oestradiol. (3) From displacement studies with unlabelled 5α-DHT the average concentration of receptor was calculated to be 12.3 fmol/mg cytosol protein (CP) in BPH, and 3.6 fmol/mg CP in muscle. Under identical conditions 39.9 fmol SHBG/mg CP and 24.1 fmol/mg CP were found in the BPH and muscle, respectively. The mean values are significantly different (P < 0.001). In plasma a mean value of 4.0 × 10−8 mol SHBG/1 was found. (4) In the BPH on average 4.43 ng 5α-DHT/g tissue and 0.23 ng T/g tissue are present, in muscle 0.45 ng 5α-DHT/g tissue and 0.71 ng T/g tissue, in plasma 0.47 ng 5α-DHT/ml and 3.89 ngT/ml. (5) Statistical calculations revealed (a) a significantly (P < 0.05) negative correlation between the endogenous 5α-DHT and T tissue levels and the available 5α-DHT receptor sites in BPH cytosol, (b) a positive correlation between plasmatic SHBG concentration and the available SHBG concentration in BPH cytosol. (6) Compared to the rat prostate, where 36 % of the incubated 5α-DHT was converted at 0°C within 20–24 h into the 5α-androstanediols, in the BPH conversion to 5α-androstanediols was negligible.
COMPARISON OF THE METABOLISM OF TESTOSTERONE UNDECANOATE AND TESTOSTERONE IN THE GASTROINTESTINAL WALL OF THE RAT IN VITRO AND IN VIVO
Authors: Geelen J. , Coert A. , Meijer R. , van der Vies J.
Published: December 2008

The metabolism of testosterone undecanoate (TU) and testosterone (T) is studied in the gastrointestinal wall of the rat in vitro. A comparison is made with the in vivo metabolism of these compounds in the rat.

The major metabolite first appearing during incubation of TU with the small intestine is T. Incubation of TU or T with the small intestine reveals a great similarity between the metabolite patterns obtained. This is also the case with the patterns derived from portal vein plasma upon oral administration of TU and T. Incubation of different parts of the gastrointestinal tract with TU or T shows that the greatest metabolic activity is located in the wall of the small intestine. Unlike T, TU is metabolized only to a small extent in the wall of the stomach and the large intestine.
THE EFFECT OF OVARIAN STEROIDS ON HYPOTHALAMIC NOREPINEPHRINE NEURONAL ACTIVITY
Authors: Munaro Norma I.
Published: December 2008

The concentration of norepinephrine and the apparent turnover of norepinephrine in the hypothalamus was studied in castrated rats and after the injection of ovarian steroids. Both parameters were found to vary not only with the hormone treatment, but also with the time of the day. Norepinephrine concentration in the anterior hypothalamus of castrated male and female rats was significantly higher in the afternoon than in the morning, but no statistical difference was observed in the concentration of norepinephrine in the posterior hypothalamus. Three days after the injection of a single dose of 20 μg oestradiol benzoate, norepinephrine concentration and apparent turnover were found with decreased significant values in the anterior hypothalamus of castrated females, killed in the afternoon. Progesterone 2 mg injected three days after the priming dose of oestradiol benzoate, produced 4 h later in the afternoon a significant rise in norepinephrine concentration and apparent turnover. These results suggest that the apparent turnover of hypothalamic norepinephrine in the afternoon is reduced by oestrogen and increased by oestrogen plus progesterone.
ANDROGEN RECEPTORS IN PROLACTIN PRODUCING PITUITARY TUMOURS IN RATS
Authors: Attramadal Arne , Naess Oddvar , Haug Egil , Hansson Vidar , Purvis Ken
Published: December 2008

The androgen receptor system in prolactin secreting oestrogen induced pituitary tumours has been studied. The tumour cytosol was found to contain specific androgen receptors binding [3H]5α-dihydrotestosterone (DHT) and [3H] testosterone (T) with high affinity and low capacity. Scatchard analysis of the saturation data for T revealed one class of high affinity binding sites. The equilibrium constant of dissociation (Kd) was ∼ 4 × 10−10 m and the number of binding sites was calculated to be 12.8 femtomoles/mg protein. The sedimentation coefficient of the androgen receptor complex in low salt sucrose gradients was ∼ 7 S, the electrophoretic mobility (RF) in 3.25 % polyacrylamide gels ∼ 0.5 and the isoelectric point 5.8. The protein nature of the receptor was indicated by the finding that protease, but not DNase and RNase, eliminated androgen binding. Furthermore, the receptor was thermolabile and functionally dependent on free SH-groups since androgen binding was eliminated by heating 45°C for 30 min) and treatment with p-chloromercuriphenyl sulphonate (1 mm). Steroid specificity was tested in vitro by examining the competing efficiency of different unlabelled steroids for the binding of [3H]T. The affinity of DHT for the receptor was approximately twice that of testosterone while the binding affinity of oestradiol-17β and progesterone was very low. Cortisol had no affinity for the androgen receptor. The dissociation of the androgen receptor complex was very slow at 0°C (t ½ > 48 h). Thus, the characteristics of the cytoplasmic androgen receptors of the prolactin producing pituitary tumours are very similar to those of the androgen receptors earlier demonstrated in the anterior pituitary, hypothalamus, ventral prostate, epididymis and testis. The presence of specific androgen receptors in prolactin producing pituitary tumours indicates that androgen is involved in the regulation of synthesis and release of prolactin.
THYROID VASCULARITY - DOCUMENTATION OF THE IODIDE EFFECT IN THYROTOXICOSIS
Authors: Brownlie B. E. W. , Turner J. G. , Ellwood M. A. , Rogers T. G. H. , Armstrong D. I.
Published: December 2008

Thyroid vascularity was measured in 101 thyrotoxic patients by analysis of 99mTc pertechnetate thyroid flow studies obtained with a gamma camera - minicomputer system. The diffusely hyperplastic goitres tended to have higher vascularity than the toxic multinodular goitres, and many of the solitary toxic nodules had vascularity results within normal limits. Potassium iodide therapy, 60 mg b. d. for 10–14 days results in a dramatic reduction in thyroid vascularity in diffuse thyroid hyperplasia and toxic multinodular goitre but the effect on toxic nodules was marginal.
INHIBITION BY SOMATOSTATIN OF MOUSE THYROID ACTIVITY FOLLOWING STIMULATION BY THYROTROPHIN, ISOPRENALINE AND DIBUTYRYL CYCLIC-AMP
Authors: Ahrén B. , Hedner P. , Melander A. , Westgren U.
Published: December 2008

The recent discovery of somatostatin-containing cells within the thyroid gland infers that somatostatin may influence thyroid activity. This possibility was investigated by measurements of radio-iodine release in mice pre-treated with 125I and T4. The animals were treated with TSH, isoprenaline or dibutyryl-cyclic AMP with and without concomitant injection of somatostatin. It was found that somatostatin reduced the blood 125I increase in response to each of the three thyroid-stimulating agents. The elimination rates of 125I-labelled T4 and T3 were unaffected by somatostatin.

The observations suggests that somatostatin may participate in the regulation of thyroid hormone secretion, by an inhibitory effect exerted within the thyroid gland.
GLUCOCORTICOID EFFECTS ON VASCULAR CONNECTIVE TISSUE DURING REPAIR. IMPORTANCE OF DOSE LEVEL AND PRE- AND POST-INJURY TREATMENT
Authors: Mathorpe R. , Garbarsch C. , Kofod B. , Lorenzen I.
Published: December 2008

Aorta of male albino rabbits were subjected to a single mechanical dilatation injury and the effects of different daily doses of prednisolone on the metabolism of collagen and glycosaminoglycans as well as on the content of alpha-amino nitrogen, RNA, DNA, water and fat and the histology of the descending thoracic aorta were analyzed 10 days after the injury. The effects of pre- and post-injury treatment with prednisolone were compared.

Prednisolone inhibited the intimal thickening. This effect was enhanced by pre-injury treatment.

Prednisolone also inhibited the biosynthesis of non-dialysable [14C]hydroxyproline-collagen, but increased the relative degradation of collagen in a dose dependent manner. The biosynthesis of glycosaminoglycans was decreased while prednisolone had no effect on the concentration and total amount of glycosaminoglycans, collagen, protein, RNA, DNA and fat. Finally the aortic content of water was decreased during treatment with prednisolone also in a dose dependent manner.

It is concluded that the action of prednisolone on vascular collagen and water during repair is dose dependent and that the inhibitory action of prednisolone on the intimal thickening is enhanced by pre-injury treatment.
INACTIVATION OF THYROTROPHIN RELEASING HORMONE BY HUMAN AND RAT SERUM
Authors: Visser T. J. , Klootwijk W. , Docter R. , Hennemann G.
Published: December 2008

The inactivation of thyrotrophin releasing hormone (pGlu-His-Pro-NH2, TRH) and its deamidated analogue pGlu-His-Pro-OH (TRH-OH) in human and rat serum has been studied using specific radioimmunoassays. No difference was apparent between human and rat serum with regard to proteolytic activity towards TRH and TRH-OH. It was found that the inactivation of both peptides is a saturable process. The disappearance of TRH was clearly inhibited by TRH-OH, luteinizing hormone-releasing hormone and dithiothreitol. The suppressive action of these compounds was observed to be dependent on their concentration. Proline and EDTA showed little inhibiting activity. Proline amide and pyroglutamic acid left the reaction unaffected. In no single instance could any production of TRH-OH from TRH be demonstrated.
DISCORDANT PATTERNS OF HYPERPROLACTINAEMIA AND GALACTORRHOEA IN SECONDARY AMENORRHOEA
Authors: Seppälä M. , Lehtovirta P. , Ranta T.
Published: December 2008

Hyperprolactinaemia occurred in 40 of 123 unselected patients (33%) with functional secondary amenorrhoea. Galactorrhoea was present only in 15 of these patients (38 %). On the other hand, galactorrhoea was found in 10 of 83 euprolactinaemic patients (12%). The frequency and severity of hyperprolactinaemia and galactorrhoea dissociated in various forms of amenorrhoea. Anorexia nervosa was characterized by euprolactinaemia and the absence of galactorrhoea. Self-induced weight loss resulted in amenorrhoea with a moderate degree of hyperprolactinaemia in 23 % of the cases. Yet, galactorrhoea was uncommon (1.6 %). Amenorrhoea following stress was also associated with moderate hyperprolactinaemia in 31 % of patients and a low frequency of galactorrhoea. By contrast, both hyperprolactinaemia and galactorrhoea occurred more frequently (36 %) and were more severe in patients who had post-pill amenorrhoea, but still 50 % of hyperprolactinaemic patients had no galactorrhoea and 28 % of euprolactinaemic patients had galactorrhoea. This discordance was accentuated in those patients who had been pregnant even if pregnancy did not immediately precede amenorrhoea. Galactorrhoea (63 %) and hyperprolactinaemia (36 %) were common in these patients and very high serum prolactin values were sometimes seen. Our results point to different mechanisms involved in the regulation of hypothalamic pituitary function and breast secretion in various forms of secondary amenorrhoea, and they may help select patients in whom the prolactin assay is likely to identify indication for specific treatment.
STUDIES ON THE PATTERN OF CIRCULATING STEROIDS IN THE NORMAL MENSTRUAL CYCLE
Authors: Nuñez M. , Aedo A.-R. , Landgren B.-M. , Cekan S. Z. , Diczfalusy E.
Published: December 2008

The plasma levels of oestrone sulphate, oestradiol sulphate, oestrone and oestradiol were studied in samples collected daily from 8 normally menstruating women throughout a complete menstrual cycle. In order to ascertain the normality of the cycles studied, LH and progesterone were also determined daily. All compounds were measured by radioimmunoassay, the sulphates after solvolysis. For the determination of the sulphates a procedure was developed which fulfilled the recognized criteria of reliability.

Both oestrone sulphate and oestradiol sulphate displayed a marked cyclic pattern, similar to and correlated with that of oestrone and oestradiol, i. e., all 4 oestrogens exhibited a marked mid-cycle peak and elevated levels during the luteal phase. The mean levels of the steroid moiety of oestrone sulphate were 10–15 times higher than those of oestrone, and 2–3 times higher than those of the 3 other oestrogens together. On the other hand, the mean levels of oestradiol sulphate were 1.2 to 4 times lower than those of oestradiol.

The ratios of the levels of various pairs of oestrogens were calculated. All pairs showed a considerable change of ratios from the early follicular phase to mid-cycle. This demonstrates that the mutual metabolic equilibria of oestrogens are different in various phases of the cycle.

Daily measurements of oestrone sulphate and oestradiol sulphate do not seem to provide a better index to predict the day of ovulation than the characteristic changes in progesterone and 17-hydroxyprogesterone levels.
PERPHENAZINE-INDUCED PROLACTIN SECRETION IN ACROMEGALY
Authors: Buckman Maire T. , Peake Glenn T.
Published: December 2008

Phenothiazine-induced prolactin secretion was studied in 6 untreated acromegalic patients with radiographic evidence of enlarged sella turcica and responses correlated with other parameters of anterior pituitary function. Five patients had normal basal serum prolactin levels and in one it was elevated. In patients with normal basal prolactin concentrations, prolactin responsiveness to perphenazine (Trilafon®) ingestion was normal in 3 and blunted in 2. The single patient with hyperprolactinaemia also demonstrated perphenazine unresponsiveness. Evaluation of the pituitary-adrenal, pituitary-thyroidal and pituitary-gonadal axes revealed a spectrum of hormonal deficiencies. Of the 3 patients with normal perphenazine-induced prolactin secretion, one had gonadotrophin deficiency, another TSH deficiency, and the remaining patient had no other demonstrable abnormality in pituitary function. In 2 patients prolactin unresponsiveness was not associated with other pituitary hormonal deficiencies. The sole patient with hyperprolactinaemia also had hypogonadotrophic hypogonadism. Thus, in acromegalic patients with radiographic evidence of enlarged sella turcicas, prolactin unresponsiveness was the commonest other abnormality observed in anterior pituitary function. In 2 patients normal prolactin responses, however, were associated with additional deficiencies. To establish pituitary functional capacity in acromegaly, the status of each pituitary hormone must be evaluated separately.
THYROLIBERIN AND GONADOLIBERIN TESTS DURING PREGNANCY AND THE PUERPERIUM
Authors: Vandalem J. L. , Pirens G. , Hennen G. , Gaspard U.
Published: December 2008

Highly specific and sensitive radioimmunoassays for HTSH, HFSH and HLH have been used in order to investigate pituitary thyrotrophic and gonadotrophic functions of pregnant and puerperal women. The radioimmunoassay system for HFSH, using reagents prepared in our laboratory, is described.

Thirty-three women were studied during pregnancy and post-partum. Forty-one TRH tests were performed. Basal levels of TSH, and increase in serum TSH after intravenous injection of TRH were similar in pregnant and puerperal women and in a control group. Thirty-three LH-RH tests were also performed. Basal levels of LH and FSH remained undetectable throughout pregnancy and in early puerperium. Furthermore, after intravenous injection of LH-RH neither LH nor FSH activity could be detected.

It has thus been demonstrated that pituitary responsiveness to TRH during pregnancy and the puerperium is similar to that of non-pregnant young women. In contrast, a complete cessation of pituitary gonadotrophic functions is observed during the same period.
INFLUENCE OF OESTROGEN ADMINISTRATION IN VIVO AND IN VITRO ON THE RELEASE AND SYNTHESIS OF LH AND FSH FROM INCUBATED PITUITARIES
Authors: Apfelbaum Marta E. , Taleisnik S.
Published: December 2008

The effect of oestrogen on the release and synthesis of LH and FSH was studied in rat adenohypophyses incubated for a period of 4 h in flasks containing 1 ml Eagle's medium. One hemipituitary was used as the experimental gland and the other half served as a control.

The spontaneous release of LH and FSH by glands from ovarectomized rats was not affected by oestradiol-17β added to the incubation medium in doses of 55, 166, 500 and 1500 ng/ml. The amount of hormones released by pituitaries from spayed rats injected with oestradiol benzoate (2.5, 5.0 and 10.0 μg/rat) 2 h or 24 h before killing the animals too was not different from that of oil-injected rats. Neither was there any effect of oestrogen when added to the incubation medium of glands from oestrogen-pre-treated rats.

However, the concentration of LH and FSH in the gland increased when oestrogen was added to the incubation medium, indicating enhanced synthesis. The effect was dose-dependent up to the dose of 500 ng/ml oestradiol but a dose of 1500 ng/ml was less effective. Increased synthesis of LH but not of FSH was also observed in incubated glands from rats injected with oestrogen 24 h before death, but no changes were seen in those of rats killed 2 h after treatment. Additive effects occurred with the in vivo and in vitro steroid treatment.

These results indicate that oestrogen favours synthesis of LH and FSH in cultured pituitaries, without affecting gonadotrophin secretion and that the changes induced in the in situ gland by oestrogen treatment are reflected by their in vitro activity.
INFLUENCE OF OESTROGEN ADMINISTRATION IN VIVO AND IN VITRO ON THE RELEASE AND SYNTHESIS OF PROLACTIN FROM INCUBATED PITUITARIES
Authors: Apfelbaum Marta E. , Taleisnik S.
Published: December 2008

The release and synthesis of prolactin were studied in incubated adenohypophyses from ovariectomized rats. After a 4 h incubation period the prolactin concentration in the medium markedly increased whereas that in the gland was reduced. However, the concentration of prolactin in the system, tissue plus medium, after 4 h was almost twice as much as that present at the beginning of incubation indicating spontaneous synthesis. This spontaneous release and synthesis of prolactin was greatly increased in incubated glands from ovariectomized oestrogen-treated rats. Oestradiol benzoate was injected in doses of 2.5, 5.0 or 10.0 μg/rat 2 or 24 h before killing the animals. Lower effects were obtained in glands from 2 h-oestradiol-pre-treated rats than from 24 h-oestradiol-primed rats. Oestradiol-17β (55, 166, 500 and 1500 ng/ml) added to the incubation medium also enhanced the release and synthesis of prolactin and the effect was more marked in glands from oestrogen injected rats than in those of non-treated animals. The increase was dose-related although the higher doses were less effective.

These results provide further evidence of the effect of oestrogen on the release and synthesis of prolactin by a direct action on the pituitary gland. They also show that oestradiol pre-treatment in vivo increase the response of the prolactin cells towards oestradiol in vitro.
HYPERCALCAEMIA DISCRIMINATION INDEX: A MULTIVARIATE ANALYSIS OF PARATHYROID FUNCTION IN 107 HYPERCALCAEMIC PATIENTS
Authors: Transbø I. , Jørgensen F. Schønau , Hornum I. , Keiding N.
Published: December 2008

The limited usefulness of radioimmunoassays of parathyroid hormone in the differential diagnosis of hypercalcaemia invites the use of methods measuring effects of parathyroid hormone (PTH). Data from 4–5-day metabolic studies in 107 hypercalcaemic patients (78 retrospective and 29 prospective cases) were combined in a hypercalcaemia discrimination index (HDI). HDI = (urine calcium (mg/24 h) x 100 x serum phosphate (mg/100 ml))/(serum total calcium (mg/100 ml) x 24-h clearance of creatinine (ml/min)) expresses in one figure the combined actions of PTH on the renal handling of calcium and on serum phosphate. A multivariate analysis confirmed that HDI offered optimal discrimination. An identical discrimination was observed in the prospective series. In the complete series HDI = 137 was the optimal discrimination point. Classification of the patients as having hyperparathyroidism (HPT) or pseudohyperparathyroidism (P-HPT) (< 137) or non-parathyroid hypercalcaemia (NON-PTH) (≧ 137) corresponded in 100 out of 107 patients (93.5%) with the final clinical diagnosis. The effects on HDI of sex, age, season, urine losses, high calcium intake and use of thiazides were also evaluated.

HDI appears to be a valuable tool in the endocrine evaluation of hypercalcaemic patients. Used in combination with radioimmunoassays measuring genuine but not ectopic PTH HDI may serve to classify hypercalcaemic patients within the following 3 subgroups: HPT, P-HPT and NON-PTH.
COMPARISON BETWEEN THE 5,6-CIS AND 5,6-TRANS ISOMERS OF 25-HYDROXYVITAMIN D3 IN CHRONIC HYPOPARATHYROIDISM
Authors: Offermann Gerd , Kraft Dieter
Published: December 2008

Five patients with chronic post-operative hypoparathyroidism were treated with 450 μg/day 5,6-trans-25-hydroxyvitamin D3 (5,6-trans-25OHD3) for 14 days, and the treatment was continued with 150 μg/day for one year. At the end of this period the patients received 450 μg/day 5,6-cis-25-hydroxyvitamin D3 (5,6-cis-25OHD3) for 14 days. Comparison of the effects of both isomers revealed a similar ability to enhance intestinal calcium absorption and to normalize serum calcium; serum phosphate and alkaline phosphatase, however, remained unaffected. Urinary phosphate and hydroxyproline excretion decreased on the cis-isomer and increased on the trans-isomer. During treatment with the lower dose of 5,6-trans-25OHD3 intestinal calcium absorption remained in the normal range for one year, whereas the serum calcium decreased to the levels observed before administration of 450 μg/day within 6 weeks. The results suggest that in hypoparathyroidism 5,6-cis-25OHD3 and 5,6-trans-25OHD3 are equally effective on serum calcium and on intestinal calcium absorption, but that their mode of action on renal phosphate handling and on calcium release from bone is different.
MAMMARY GROWTH AND FUNCTION AND PITUITARY PROLACTIN SECRETION IN FEMALE NUDE MICE
Authors: Nagasawa Hiroshi , Yanai Reiko
Published: December 2008

Mammary structural growth in the wholemount preparation, content and synthesis of mammary DNA and RNA estimated by the incorporation of [3H]thymidine and [14C]uridine, pituitary and plasma levels of prolactin and weights and histological structures of some organs of female nude mice (nu/nu) were compared to those of the control (nu/+) with the same genetical background (BALB/c). Both at 3 months of age and on day 1 of lactation, the weights per 100 g body weight of adrenals, spleen and liver of nu/nu mice were significantly higher than those of nu/+ mice. Mammary growth stimulation by pituitary graft was much more marked in nu/nu mice than in nu/+ mice. Slight differences between groups were found in the pituitary and plasma levels of prolactin, in the histological structures of ovaries as well as of the adrenals and thyroids and in the pattern of oestrous cycles. On the other hand, the content and synthesis of mammary DNA at 3 months of age and content and synthesis of both DNA and RNA and RNA/DNA ratio on day 1 of lactation were significantly higher in nu/+ mice than in nu/nu mice. All findings suggest that thymus deficient immunosuppression has deleterious effects on mammary growth and function without its alteration in the secretion of prolactin and oestrogen and probably through its decrease in mammary responsiveness to mammotrophins.