bluuebunny/crossref_metadata_2025 huggingface dataset:
Climacteric symptoms, fat mass, and plasma concentrations of LH, FSH, Prl, oestradiol-17β and androstenedione in the early post-menopausal period
Authors: Hagen C. , Christiansen C. , Christensen M. S. , Transbøl I.
Published: December 2008

The relations between climacteric symptoms, fat mass, time after the menopause, and plasma concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin (Prl), oestradiol-17β, and androstenedione were studied in 313 normal females in their early post-menopausal period.

The mean age of the women was 50 years (45–54 years, range) and the time elapsed since the last menstrual bleeding was 19.8 months (4–46 months). Most women had mild to moderate climacteric complaints. The participants were examined and filled in a questionnaire containing the 11 symptoms of Kupperman index.

A total of 61% of the women complained of hot flushes and from 9% to 44% complained of the remaining 10 Kupperman symptoms. Women with hot flushes (n = 196) had a higher mean score (P < 0.01) of the remaining symptoms than women without (n = 117). Plasma concentrations of LH and FSH were significantly higher and levels of oestradiol-17β and androstenedione were significantly lower in women complaining of hot flushes than in women without. Plasma levels of FSH was significantly (P < 0.05) higher and levels of oestradiol17β was signficantly (P < 0.01) lower in women with insomnia than in women not complaining of this symptom and women with depression had significantly (P < 0.01) higher Prl levels than women without. The months since the menopause were related to plasma levels of FSH (r = +0.216, P < 0.01) and oestradiol-17β levels (r = −0.306, P < 0.001) but not to plasma concentration of LH, Prl and androstenedione. Fat mass was related to plasma FSH and androstenedione concentrations and correlation was found between oestradiol-17β and androstenedione (r = +0.334, P < 0.001). Surprisingly, no correlation between hot flushes and fat mass was found.
Post-menopausal concentrations of plasma oestradiol, oestrone, FSH and LH and of total urinary oestradiol and oestrone after a single sublingual dose of oestradiol-17β
Authors: Fiet J. , Hermano M. , Witte J. , Villette J. M. , Haimart M. , Gourmel B. , Tabuteau F. , Rouffy J. , Dreux C.
Published: December 2008

We report the effects of sublingual absorption of a single dose (0.5 mg) of oestradiol-17β (E2) in 8 post-menopausal women, on plasma E2 and oestrone (E1), urine elimination of total E2 + E1 and on plasma FSH and LH.

The results show that sublingual absorption of E2 occurs and that plasma concentrations of E2 obtained (between 133.2 to 320 pmol/1) in this way were higher than those obtained after percutaneous absorption of a single dose (3 mg)of E2.

The ratio E1/E2 in plasma is close to that of pre-menopausal women.
Circadian rhythm of serum progesterone levels in human pregnancy and its relation to the rhythm of cortisol
Authors: Junkermann H. , Mangold H. , Vecsei P. , Runnebaum B.
Published: December 2008

Progesterone and cortisol were measured in the peripheral blood of pregnant women using radioimmunoassay. Ten women were between 18 and 25 weeks of pregnancy and 10 women were between 32 and 38 weeks of pregnancy. Blood for the hormone determinations was drawn at hourly intervals. A significant circadian progesterone rhythm was found with the nadir at 8.00 h and the peak around midnight. The progesterone rhythm showed a significant inverse relation to the cortisol rhythm (τ = −0.310). No difference was detected between the two groups for progesterone rhythm or its inverse relation to the cortisol rhythm.
Large annual variation in photoperiodicity does not affect testicular endocrine function in man
Authors: Huhtaniemi Ilpo , Martikainen Hannu , Tapanainen Juha
Published: December 2008

The purpose of the present study was to elucidate the possible influence of large differences in circannual photoperiodicity on human testicular activity. Serum testosterone was measured once a month in a group of 24 healthy young adult men for a period of 13 months in northern Finland, where the day length is 22 h in mid-summer and 3.5 h in mid-winter. The monthly levels of serum testosterone varied between 11.3 ± 0.93 and 13.0 ± 1.2 nmol/l (SE, n = 24), with no significant differences between individual months. The amplitude of variations in serum testosterone was ± 7% of the annual mean, which was less than in studies reported earlier from central Europe. Our negative findings suggest that the extreme circannual changes in the amount of day-light do not play an obvious role in the regulation of human testicular androgen production.
Lack of influence of the anabolic steroid nandrolondecanoate on bone metabolism
Authors: Bijlsma J. W. J. , Duursma S. A. , Bosch R. , Huber O.
Published: December 2008

Eleven male patients with rheumatoid arthritis were treated with the anabolic steroid nandrolondecanoate and parameters of calcium and bone metabolism were studied. No changes were found in the concentrations of calcium, phosphorus or hydroxyproline in serum and urine (corrected for the creaturia). A significant decrease (P < 0.01) was observed in the levels of alkaline phosphatase, but this was attributed to a change in liver enzymes, because the gamma glutamyl transpeptidase fell. Acid phosphatase levels showed an increase, possibly as a result of an effect of nandrolondecanoate on the prostate. No change was found during treatment in the serum levels of parathyroid hormone, calcitonin, 25 hydroxyvitamin D, 24,25 dihydroxyvitamin D and 1.25 dihydroxyvitamin D. A seasonal fluctuation was observed for 25 hydroxyvitamin D and 24,25 dihydroxyvitamin D, but not for 1,25 dihydroxyvitamin D. It was concluded that short-term treatment with the anabolic steroid nandrolondecanoate did not result in changes in parameters of calcium and bone metabolism.
Effect of brain monoamines on the secretion of adrenocorticotrophic hormone
Authors: Amar Alka , Mandal S. , Sanyal A. K.
Published: December 2008

The role of brain monoamines (5-HT, NA and DA) in the secretion of adrenocorticotrophic hormone (ACTH) was studied in view of contradictory reports. Plasma corticosterone levels and the rate of synthesis of corticosterone in vitro by the adrenal gland were estimated in albino rats and have been taken as the index of ACTH activity. These estimations were done in unstressed and stressed, and in untreated and treated rats. Drugs were administered intracerebroventricularly to the rats to cause selective degeneration of tryptaminergic, noradrenergic or dopaminergic neurons.

The results show that plasma corticosterone levels and the rate of synthesis of corticosterone were significantly decreased after selective degeneration of tryptaminergic neurons in unstressed rats. After selective degeneration of either tryptaminergic or noradrenergic neurons, the acute increase in the plasma corticosterone levels and rate of synthesis of corticosterone in vitro by adrenal glands in stressed rats were significantly inhibited. These results have been interpreted to suggest that the central tonic control on adrenal glands may be 5-HT mediated and that during stress ACTH secretion may be both 5-HT and NA mediated. DA does not seem to have significant role in the regulation of ACTH secretion.
Secretion rates of thyroxine, triiodothyronine, and reverse triiodothyronine in man during surgery
Authors: Tegler Lennart , Gillquist Jan , Lindvall Roland , Almqvist Sven
Published: December 2008

The secretion rates of T4, T3, and rT3 were studied in experiments of short duration by a new method based on determinations of the hormone difference across the thyroid combined with simultaneous electromagnetic thyroid blood flowmetry during surgery in 70 euthyroid patients.

The secretion rate of T3 was similar in normal thyroid tissue and nodular goitre, but those of T4 and rT3 were lower in nodular goitre and solitary adenoma (P < 0.05). In 61 patients with normal thyroid tissue or nodular goitre the secretion rates during surgery (mean ± sem) were for T4 222 ± 28 nmol/day, for T3 27.4 ± 3.1 nmol/day, and for rT3 3.5 ± 0.5 nmol/day. In relation to the individual T4 secretion rate, the secretion rate of T3 was 12.5 ± 3.0% and that of rT3 1.2 ± 0.9%.

In these short-term experiments we found a secretion rate for T4 during operation about 50% greater than in earlier long-term kinetic studies, but which tallied with a recent report using a 4-compartment model. For T3 and rT3 it was 2–3 times greater than earlier estimates. The secretion was estimated to be 50% of the total production rate for T3 and 6% for rT3. If proportional adjustment were performed to yield a T4 secretion of about 130 nmol/day, T3 and rT3 secretion rates would still be greater than earlier reported.
Growth and maturation in pseudo-hypoparathyroidism; a longitudinal study in 5 patients
Authors: de Wijn E. M. , Steendijk R.
Published: December 2008

In 4 girls and 1 boy with pseudo-hypoparathyroidism growth and physical maturation were followed longitudinally for 7 – 13 years until adult height had been reached. As a result of early puberty and cessation of growth all patients were relatively shorter as adults than in their childhood years. The difference between average height at the age of 8.0 years and average adult height was 2.25 sd. This observation offers an explanation for the finding in the literature that short stature is more common in adults with this disease than in children. Skeletal age was advanced in all cases and the development of the tubular bones of the hand was more advanced than the development of the round bones. It is possible that this difference resulted from inappropriately early closure of the epiphyseal discs of disproportionally short metacarpals and phalanges. On the other hand it may be an aspecific phenomenon of advanced skeletal maturation.
Serum adrenal androgens in hyperprolactinaemic women prior to, during, and after chronic treatment with bromocriptine
Authors: Evans William S. , Schiebinger Rick J. , Kaiser Donald L. , Nunley Wallace C. , Loriaux D. Lynn , MacLeod Robert M. , Thorner Michael O.
Published: December 2008

Conflicting data exist in the literature regarding serum adrenal androgen concentrations in hyperprolactinaemic states and the influence or lack thereof of dopaminergic drugs on the androgens. We carried out a prospective study on 7 hyperprolactinaemic women, none of whom had clinical features commonly associated with elevated androgens. Serum levels of prolactin (Prl), cortisol, androstenedione, dehydroepiandrosterone (DHA) and dehydroepiandrosterone sulphate (DHAS) were measured basally, at 3, 6, and 12 months during chronic bromocriptine therapy, and 2 months following withdrawal of the drug. Prior to bromocriptine therapy, and despite a mean serum Prl of 178 ng/ml, all values of cortisol, androstenedione and DHA were normal as were 6 of 7 DHAS values. During treatment with bromocriptine for 12 months, the mean Prl level dropped into the normal range, but levels of cortisol, androstenedione and DHA remained unchanged. DHAS was significantly lower at 12 months when compared to initial levels but was not significantly different at 3 and 6 months. No significant differences were observed in cortisol or androgens 2 months after termination of the bromocriptine compared to basal levels. A significant correlation was observed between cortisol and both androstenedione (P = 0.0042) and DHA (P = 0.0002) but not with DHAS. A significant correlation was found to exist between Prl and DHAS (P < 0.0001) but not with androstenedione or DHA. Thus, we found normal levels of serum adrenal androgens in 6 of 7 hyperprolactinaemic women, none of whom demonstrated clinical features of the polycystic ovary syndrome. These data suggest: 1) increased basal adrenal androgens in hyperprolactinaemia may not be as common as previously reported; 2) androstenedione and DHA do not correlate with Prl; 3) DHAS is correlated with Prl. Although it appears that DHAS and prolactin concentrations are related, the mechanism underlying this relationship remains uncertain.
Effects of oestradiol on sex hormone binding globulin
Authors: Odlind Viveca , Elamsson Kerstin , Englund Doris E. , Victor Arne , Johansson Elof D. B.
Published: December 2008

Sex hormone binding globulin (SHBG) levels were studied for possible effects of oestradiol-17β on SHBG. No change in SHBG plasma was recorded during normal menstrual cycles or during treatment with oestradiol-17β to menopausal women. However, gonadotrophin treatment to amenorrhoeic women to induce ovulation resulted in high oestradiol concentrations and a pronounced increase in SHBG was found during the luteal phase of these cycles. A marked increase of SHBG was also recorded in a woman with pronounced fluctuations of oestradiol during treatment with levonorgestrel sc implants for contraception. In conclusion, effects on SHBG were only found when extraordinarily high levels of plasma oestradiol were recorded.
A gonadotrophin-releasing hormone (GnRH) antagonist inhibits GnRH- but not LH-induced meiosis in follicle-enclosed rat oocytes in vitro
Authors: Ekholm C. , Hillensjö T. , Le Maire W. J. , Magnusson C. , Rani C. S. Sheela
Published: December 2008

Previous studies have shown that gonadotrophin-releasing hormone (GnRH) can induce resumption of meiosis in follicle-enclosed rat oocytes. In the present study a GnRH antagonistic analogue ([d-pGlul, d-Phe2,-d-Trp3,6]LRF) was found to effectively abolish the stimulatory effect of a GnRH agonist upon resumption of meiosis and lactate accumulation in isolated pre-ovulatory rat follicles but the have no effect on LH stimulation of these parameters. It is concluded that although LH and GnRH can evoke a similar response they act through separate receptor sites and that it is unlikely that GnRH mediates the effect of LH on meiosis or glycolysis.
Increase of ovarian progesterone secretion by β2-adrenergic stimulation in oestrous rats
Authors: Zsolnai Béla , Varga Bertalan , Horváth Edit
Published: December 2008

Oestrous rats were anaesthetized with pentobarbital and one of the femoral arteries, femoral veins and utero-ovarian veins were cannulated. Five min blood fractions were collected from the ovary for 50 min. Following two control fractions fenoterol, noradrenaline, isoproterenol (0.5 μg/min) or 0.9% NaCl (0.02 ml/min) were infused iv for 40 min. In a group of oestrous animals fenoterol was given locally to the ovarian bursa. Blood pressure and the ovarian venous outflow were continuously recorded and blood levels of progesterone (P) and oestradiol-17β (E2) were determined by RIA.

Fenoterol administered iv increased P secretion without altering ovarian blood flow, whereas noradrenaline and isoproterenol had no effect on P secretion. Fenoterol administered locally stimulated both P and E2 secretion, and this was prevented by iv infusion of propranolol.

It is suggested that ovarian β2-adrenergic receptors have a regulatory role in ovarian hormone secretion.
Progesterone facilitates the LRH releasing action of oestrogen
Authors: Miyake A. , Tasaka K. , Kawamura Y. , Sakumoto T. , Aono T.
Published: December 2008

The effects of progesterone (P) on the release of LRH and LH were examined in a sequential double chamber superfusion system by superfusing the medial basal hypothalamus (MBH) and/or pituitaries excised randomly from cycling female rats. Addition of 10 μl of 10−6 m oestradiol (E2) to the first chamber resulted in a gradual and significant (60–160%) increase in LH release above the pre-injection level from the pituitary in series with MBH. Administration of 10−8 m P after 10−6 m E2 caused a prompt and marked increase (300%) of LH (P < 0.05), whereas 10−8 m P alone had no effect. Administration of 10−6 m E2, 10−8 m P or E2 plus P did not significantly change LH secretion from the pituitary superfused alone. The concentration of LRH in the efflux was significantly increased (150–200%) 150 min after 10−6 m E2 administration. P administration after E2 injection produced a prompt and significant increase of LRH and the increase of LRH (300–600%) was 2–3-fold that produced by E2. P alone had no effect. These data clearly indicate that P enhances E2-induced LH release by increasing LRH secretion from the MBH.
Hypothyroidism following subacute thyroiditis
Authors: Tikkanen Matti J. , Lamberg B.-A.
Published: December 2008

The occurrence of permanent overt or subclinical hypothyroidism following subacute thyroiditis (SAT) was studied in 32 patients during 0.75–13 years (mean 4.2 years) of follow-up. Permanent hypothyroidism developed in 2 patients in whom a characteristic feature was persistence of circulating thyroid antibodies in high titres from the onset of SAT indicating the presence of autoimmune thyroiditis. One also showed cytological evidence of autoimmune thyroiditis. In another patient subclinical hypothyroidism demonstrated by an exaggerated TSH-response to TRH, persisted after hemithyroidectomy during the acute phase. In addition, transient overt hypothyroidism developed immediately after the acute phase in 3, and subclinical hypothyroidism in 2 patients. Apart from the 2 patients with evidence of autoimmune thyroiditis, circulating thyroid antibodies were found in 15 others. The titres were usually low and disappeared in most cases after a transient rise. It is concluded that permanent hypothyroidism is likely to develop after SAT only in the presence of autoimmune thyroiditis or after thyroid surgery.
Suppressor T lymphocyte function in Graves' disease
Authors: Hallengren Bengt , Forsgren Arne
Published: December 2008

To explore suppressor T lymphocyte function in Graves' disease, studies were performed in one group of patients in the hyperthyroid state and in another group in the euthyroid state after treatment. Peripheral blood lymphocytes were cultured for 1–7 days., Pokeweed mitogen (PWM; 1.25 μg/ml) was added at the initiation of the cultures or after 24 h. The degree of lymphocyte activation was assessed by measurements of the cellular uptake of [3H]thymidine and expressed in counts per minute (cpm). The suppressor lymphocyte function was estimated by a quotient between the maximum cpm values from cultures with and without pre-incubation.

For the hyperthyroid group (n = 15) the quotient was 1.00 ± 0.07 (mean ± sem), for the euthyroid patient group (n = 21) 1.12 ± 0.05 and for the healthy control group (n = 21) 1.37 ± 0.08. There was a significant difference between the quotients for the control group and the hyperthyroid (P < 0.01) as well as the euthyroid (P < 0.05) patient group. The quotients for the two groups of patients did not differ significantly.

In conclusion, the present study supports the view of a defect in suppressor T lymphocyte function in patients with Graves' disease in the hyperthyroid state and indicates that this defect can persist in the euthyroid state after treatment.
Mast cell hyperplasia during goitrogen - induced thyroid growth — a quantitative study
Authors: Wynford-Thomas D. , Stringer B. M. J.
Published: December 2008

This paper describes the effect of long-term goitrogen-administration on the mast cell population of the rat thyroid. Animals were treated with the goitrogen aminotriazole at a dose sufficient to block thyroid hormone synthesis completely, and compared after 80 days with a control group. Serum TSH was measured by radioimmunoassay, and mast cell number quantified from specially-stained tissue sections using appropriate stereological methods.

Goitrogen treatment led to a 9-fold increase in serum TSH and an 8-fold increase in thyroid weight. Mast cell number per unit volume of thyroid decreased, but total numbers per gland increased 4 to 5 fold. There was a significant fall in mean mast cell size.

The work demonstrates conclusively that mast cell hyperplasia occurs during goitre formation and provides a method for its quantitative assessment.

The possible mechanisms and significance of thyroid mast cell proliferation are discussed.
Characteristics of rT3 5'-monodeiodination in rat brain: comparison with T4 and T3 5-monodeiodinations
Authors: Tanaka Kiyoshi , Inada Mitsuo , Mashio Yasuo , Ishii Hitoshi , Naito Koichi , Nishikawa Mitsushige , Takahashi Kiyoyuki , Imura Hiroo
Published: December 2008

The present study revealed the existence and some characteristics of rT3 5'-deiodinase in rat brain by measuring the production of 3,3'-T2 from rT3 by radioimmunoassay. The conversion of rT3 to 3,3'-T2 was dependent on the duration of the incubation, tissue amount, temperature and pH (the optimal pH was 8.0), suggesting its enzymatic nature. Apparent Km was estimated to be 0.16 μm and the Vmax was 139.3 fmol/mg protein/min. The converting activity was dependent on the concentration of dithiothreitol (DTT). In contrast to T4 or T3 5-deiodinase, rT3 5'-deiodinase activity in the rat brain was the highest in cerebellum and the activity was low in the neonatal rat brain. Moreover, the 5'-deiodinase activity was inhibited by propylthiouracil (PTU). These differences between rT3 5'-deiodinase and T4 or T3 5-deiodinase suggest that different deiodinases are present in rat brain, and that local conversion of thyroid hormone is important for its action in the central nervous system.
Impaired subcutaneous absorption of insulin in 'brittle' diabetics
Authors: Home P. D. , Massi-Benedetti M. , Gill G. V. , Capaldo B. , Shepherd G. A. A. , Alberti K. G. M. M.
Published: December 2008

Twenty-four hour plasma free insulin and blood glucose and intermediary metabolite profiles have been measured in 6 C-peptide deficient 'brittle' diabetic patients, during continuous sc and im insulin infusion. During sc infusion free insulin profiles were erratic and unpredictable. Mean 24 h blood glucose levels were raised at 12.6 ± 2.1 (se) mmol/l, and 3-hydroxybutyrate at 0.24 ± 0.08 mmol/1. Blood lactate (1.88 ± 0.18 mmol/l) and glycerol (0.084 ± 0.007) were also elevated. Insulin (im) restored free insulin profiles to the normal pattern as found in 'stable' diabetics on sc infusion, with characteristic post-meal peaks (49 ± 7, 103 ± 35, and 95 ± 34 mU/l) and stable night-time levels. Mean 24 h blood glucose was 6.7 ± 1.1 mmol/l (P < 0.05 compared to sc infusion) and 3-hydroxybutyrate 0.07 ± 0.02 mmol/l (P < 0.05). Blood lactate (1.67 ± 0.08 mmol/l) and glycerol (0.10 ± 0.02 mmol/l) levels remained abnormal. The ratio of plasma free insulin to insulin dose administered was significantly higher during im infusion. In the 6 'stable' diabetics on sc insulin infusion good blood glucose control (7.1 ± 0.9 mmol/l) was accompanied by clear post-prandial insulin peaks, and stable nocturnal levels. The results strongly suggest that in one category of 'brittle' diabetics there is defective and erratic sc insulin absorption.
The pituitary-testicular axis of uraemic subjects on haemodialysis and continuous ambulatory peritoneal dialysis
Authors: Semple C. G. , Beastall G. H. , Henderson I. S. , Thomson J. A. , Kennedy A. C.
Published: December 2008

Pituitary-testicular function was evaluated in 18 patients with chronic renal failure, 9 treated by maintenance haemodialysis (HD) and 9 by continuous ambulatory peritoneal dialysis (CAPD), and compared with a non-uraemic control group. Serum total testosterone and the free testosterone index were significantly low in both dialysis groups. Basal FSH and LH levels were elevated but this reached significance only with regard to LH. The responses of both FSH and LH to the iv administration of LRH were normal. There was no significant difference between the CAPD and HD groups in any of the hormonal parameters estimated. While CAPD may improve control of some metabolic parameters when compared with HD, it does not improve the function of the pituitary-testicular axis.
Potent 48 hours inhibition of prolactin secretion by pergolide in hyperprolactinaemic women
Authors: L'Hermite Marc , Debusschere Pierre
Published: December 2008

The duration of the inhibition of Prl secretion by pergolide, a new dopaminergic ergoline, was investigated in 5 hyperprolactinaemic women after a single oral 50 μg dose. In each subject, blood samples were collected every 2 h for 18–24 h to establish baseline Prl level and then every 3 h for 48–51 h after pergolide administration. In each subject, levels were potently suppressed by at least 80% of baseline and brought down to the normal range. Prolactin suppression was quite sustained throughout the study period in 4 patients and to a lesser degree in the remaining subject.

This potent long-lasting inhibition of Prl secretion should enhance the efficacy and acceptability of the chronic treatment of hyperprolactinaemia with this new dopamine agonist and, for example, allow drug intake only once every other day.
Impaired pituitary response to bromocriptine suppression: reversal after bromocriptine plus tamoxifen
Authors: Völker Wernfrid , Gehring Werner G. , Berning Renate , Schmidt Rüdiger C. , Schneider Jörg , von zur Mühlen Alexander
Published: December 2008

This study was designed to clarify whether previously resistant cases of adenomatous hyperprolactinaemia to bromocriptine might be improved by additive tamoxifen therapy. Ten hyperprolactinaemic women under bromocriptine (2.5–10 mg) with hypophyseal tumours of different extent were treated with a combined therapy of bromocriptine and tamoxifen (10–20 mg). Two of them had undergone incomplete resection of chromophobe adenomata. The others refused surgery or irradiation. Two other women without basal therapy because of side effects from bromocriptine, received the combined therapy from the beginning of the study. In 6 out of 10 women the addition of tamoxifen resulted in a marked suppression of prolactin serum values. Amenorrhoea and glactorrhoea ceased in 4 of them. One woman conceived. One reported a marked improvement of libido. One stated that side effects under bromocriptine disappeared through the addition of tamoxifen. The 2 women who previously were suffering from side effects were able to take bromocriptine when tamoxifen was added. Four patients were non-responders. Serum prolactin remained unchanged as well as the clinical follow-up. The effectiveness of the combined therapy was not related to the extent of the tumour or to the clinical or biochemical baseline date.

We conclude that the suppressive effect of bromocriptine on prolactin secretion is enhanced by the addition of tamoxifen in most cases of adenomatous hyperprolactinaemia. Side effects of bromocriptine are considerably reduced. Anti-oestrogens are competitive inhibitors of the binding of oestradiol to the receptor. Oestrogen play an important role in the development of prolactin secreting adenomata. Our finding of responders and non-responders to tamoxifen suggests that the anti-oestrogen competes for greater or lesser concentrations of receptor sites in prolactinomata.
Time course of inhibition of synthesis and basal release of FSH from pituitary glands of female rats by bovine follicular fluid in vitro
Authors: Jenner A. A. J. , de Koning J. , van Rees G. P.
Published: December 2008

Inhibin-like activity in steroid-free bovine follicular fluid (bFF) is demonstrated using an in vitro technique with hemi-pituitary glands from intact female (second day of dioestrus) and ovariectomized rats: synthesis as well as basal release of FSH, but not of LH, are inhibited profoundly. The results confirm and extend data from other investigators on the action of inhibin-like material. The effect of the inhibin-like activity is shown to be reversible, as synthesis and the rise of basal release are restored when bFF is withdrawn from the incubation medium. Synthesis of FSH seems to be inhibited earlier than basal release, and it is suggested that the inhibin-like material acts only directly on FSH synthesis. Some possibilities of the mechanisms of action of inhibin-like activity are discussed.
A longitudinal study of serum TSH, and total and free iodothyronines during normal pregnancy
Authors: Weeke J. , Dybkjær L. , Granlie K. , Jensen S. Eskjær , Kjærulff E. , Laurberg P. , Magnusson B.
Published: December 2008

Serum T4, T3, rT3, free T4, free T3 and TSH were measured during and after normal pregnancy in 20 women. Special methodological precautions were taken to avoid interference of other hormones and protein alterations in the assays. Serum T4 and T3 were steadily increasing during the last part of the 1st trimester, and remained high and nearly stable during the 2nd and 3rd trimester of the gestation period. The high levels were approximately 1.5 times the values measured 10 weeks post-partum. Serum rT3 was elevated already during the last part of the 1st trimester and remained high throughout pregnancy, compared to the post-partum value. Serum free T4 and free T3 were slightly elevated in early pregnancy. The values decreased gradually during pregnancy and were slightly depressed during the 3rd trimester. A gradual increase in serum TSH was observed during pregnancy and the 2nd and 3rd trimester values were significantly higher than the post-partum value. The mean values for serum TSH, free T4 and free T3 remained always well within the normal range. Thus small variations in serum free iodothyronines and TSH occur during normal pregnancy, the alterations observed in the last trimester of the gestation period resembling those of a slight thyroid insufficiency. These trends in variation of the reference values are worth to remember in the diagnosis of borderline hypo- or hyperthyroidism and in the balanced treatment of pregnant women with thyroid dysfunction.
Impaired secretion of TSH in critically ill patients with 'low T4-syndrome'
Authors: Vierhapper Heinrich , Laggner Anton , Waldhäusl Werner , Grubeck-Loebenstein Beatrix , Kleinberger Gunther
Published: December 2008

Thyroid and pituitary function was studied in 10 male and 6 patients female during critical non-endocrine disease. Low concentrations of TT3 were observed in each case. Seven patients out of whom 3 survived, presented with low levels of TT4 due to deficiency in TBG in the presence of normal values of FTI and FT4, whereas a 'low T4-syndrome', characterized by low concentrations of both TT4 and FT4 was seen in 9 patients, 8 of whom died 1 to 16 days after evaluation of pituitary function. A diminished response of TSH to iv TRH (400 μg), as observed in 4 patients with normal FT4 and in all patients with 'low T4-syndrome', was not accompanied by a concomitant lack in stimulated release of LH, FSH and Prl in the majority of cases. However, the secretory maximum of LH and FSH following stimulation by LRH (100 μg iv) was delayed in 10 and in 9 patients, respectively, including patients both with normal and subnormal concentrations of FT4. From the above it appears that low stimulated concentrations of TSH in the presence of subnormal concentrations of FT4 indicate an extremely poor prognosis in critically ill patients. The abnormal behaviour of TSH in this group of patients cannot be explained by generalized pituitary insufficiency or by an increase in FT4.
Effects of seven different oestrogen sulphates on uterine growth and on progesterone receptor in the foetal uterus of guinea pig after administration to the mother
Authors: Pasqualini J. R. , Lanzone A. , Tahri-Joutei A. , Nguyen B. L.
Published: December 2008

The biological effect of seven different oestrogen sulphates: oestrone-3-sulphate (E1-3-S), oestradiol-3-sulphate (E2-3-S), oestradiol-17-sulphate (E2-17-S), oestradiol-3,17-disulphate (E23,17-DS), oestriol-3-sulphate (E3-3-S), oestriol-17-sulphate (E3-17-S), oestriol-3,16,17-trisulphate (E3-3,16,17-TS), was studied in the foetal uterus of guinea pig (55–65 days of gestation) after sc administration for 3 consecutive days of each sulphate to the mother. On day 4, two response parameters were investigated, the uterotrophic effect and the action on the progesterone receptor. The monosulphates at the C3 position of the oestrogens (E1-3-S, E2-3-S and E3-3-S) provoked an increase in uterine weight of 1.9–2.4 times in relation to the non-treated animals. These oestrogen sulphates also very significantly stimulated the number of progesterone specific binding sites, 7–10 times in relation to the non-treated animals. On the other hand, when the sulphate was at C17 of the oestrogens (E2-17-S, E3-17-S, E2-3, 17-DS, E3-3,16,17-TS), very little or no effect on the foetal uterus was observed on the two parameters studied.

It is concluded that oestrogen (oestrone, oestradiol, oestriol) sulphates in position C3 can be involved in the biological response to the hormone and it is suggested that the effect is carried out after the hydrolysis of the sulphate. On the other hand, sulphates in C17 are not hydrolysed and no significant biological effects were observed in the uterine growth or in the progesterone receptor.
β-endorphin-like peptides in autopsy pituitaries from adults, neonates and foetuses
Authors: Vuolteenaho Olli , Leppäluoto Juhani , Höyhtyä Matti , Hirvonen Jorma
Published: December 2008

The presence of β-endorphin in human pituitary was studied using radioimmunoassay, opiate receptor binding assay and different chromatographic methods. Adult human pituitaries were found to contain 291 ± 59 μg/g β-endorphin immunoreactivity, of which 15–45% eluted like β-endorphin in Sephadex G-75 gel filtration. The yield of β-endorphin immunoreactivity was found to be dependent of the extraction method used, but the relative proportion of the different immunoreactive components (proopiomelanocortin, β-lipotrophin and β-endorphin) was approximately identical irrespective of the extraction method. No correlation was observed between the time lag from death to autopsy (within 7 days) and either the total amount of β-endorphin immunoreactivity or the β-lipotrophin/β-endorphin ratio in the acid extracts of human pituitaries. Repeated freezing and thawing was found to cause a progressive loss of extractable β-endorphin immunoreactivity so that the smaller molecular weight material (β-endorphin) disappeared more rapidly than the higher molecular weight material (β-lipotrophin). Pituitaries from neonates and foetuses were found to contain proportionally more β-endorphin than pituitaries from adults (β-lipotrophin/β-endorphin ratio was 2.76 ± 0.43 in adults, 0.93 ± 0.11 in neonates and 0.47 ± 0.09 in foetuses). β-endorphin-like material from gel filtration was found to separate into two components on SP-Sephadex C-25 cation exchange chromatography. The more basic of these eluted identically with synthetic human β-endorphin in reversed phase HPLC, displaced tracer parallelly both in radioimmunoassay and opiate receptor binding assay and had a receptor binding potency not significantly different from that of synthetic β-endorphin. The less basic component has a smaller molecular weight than β-endorphin and represents a formerly unrecognized human pituitary endorphin-like peptide. The results suggest that β-endorphin is a naturally occurring peptide in human pituitary.
Anti-thyrotrophin receptor antibodies in Graves' disease as demonstrated directly by immunoprecipitation assay
Authors: de Bruin Tjerk W. A , van der Heide Daan , Krol Maria C.
Published: December 2008

An immunoprecipitation assay was developed to determine the presence of antibodies against human TSH1 receptors. With this assay we were able to demonstrate that in comparison with sera from normal controls, 24 out of 30 (80%) sera from patients with untreated Graves' disease could immunoprecipitate more [125I]TSH-TSH receptor complexes. In 9 assays, an average of 14.1 ± 3.7% (sd) of the [125I]TSH-TSH receptor complexes was immunoprecipitated by the 30 Graves' sera vs 9.8 ± 3.0% by the normal pool serum (n = 23) (P < 0.001) and 7.7 ± 2.8% by the 22 normal sera (P < 0.001). One serum of the 24 positive Graves' sera was studied in detail. The results suggest that this serum contained an anti-TSH receptor auto-antibody directed towards a different determinant on the TSH receptor than the TSH binding site.
Studies of catecholamine effect on cyclic AMP in human cultured thyroid cells: their interaction with thyrotrophin receptor
Authors: Toccafondi Roberto S. , Brandi Maria Luisa , Rotella Carlo M. , Zonefrati Roberto
Published: December 2008

Even though adrenergic nerve terminals between and around thyroid follicles and catecholamine stimulation of thyroid adenylate cyclase have been reported, there is no uniform concept on catecholamine interaction with thyrotrophin (TSH) receptors. Therefore, the effect of catecholamines on TSH-stimulated cyclic AMP (cAMP) accumulation in human follicular thyroid cells has been investigated, to thus eliminating the extrathyroidal actions of catecholamines.

Epinephrine, norepinephrine and isoproterenol appeared to be rapid and potent stimulators of intracellular cAMP accumulation, the half maximum increase doses being 4 × 10−7m, 1 × 10−5m and 5 × 10−7m, respectively. While propranolol (1 × 10−5m) prevented the stimulatory effect of catecholamines and failed to inhibit the effect of bovine TSH, phentolamine (1 × 10−5m) enhanced the potency of norepinephrine and bovine TSH, leaving that of epinephrine unchanged. The effects of epinephrine (2 × 10−8m) and isoproterenol (2 × 10−8m) were additive to that of bovine TSH (0.5 mU/ml), but the effect of simultaneous stimulation with norepinephrine (5 × 10−7m) and bovine TSH (0.5 mU/ml) was lower than expected. Prenalterol, a selective β1-agonist, did not stimulate cAMP accumulation, while terbutaline, a selective β2-agonist, exerted a potent stimulation. Metoprolol, a selective β1-adrenergic blocker, did not affect the response of thyroid follicular cells to isoproterenol.

These results demonstrate the existence of β-adrenergic receptors in human thyroid follicular cells, mainly of the type β2, apparently not correlated with TSH receptor. The existence of α-adrenergic receptors which counter-regulate TSH functional responses in human thyroid follicular cells is suggested.
The accumulation of [35S]methimazole by human and rat lymphocytes
Authors: Shewring G. S. , Lazarus J. H.
Published: December 2008

The accumulation of 35S labelled methimazole (MMI) was examined in lymphocytes. No uptake of label was found in peripheral blood lymphocytes (PBL) from normal control subjects after in vitro incubation with the drug. Following administration of [35S]MMI to patients with Graves' hyperthyroidism PBL cell to plasma (C/P) 35S activity was greater than 1 in 4 of 11 patients and only in 1 of 7 other patients undergoing thyroidectomy. Thyroid lymphocytes from 2 of these patients showed some accumulation of activity.

Following administration of [35S]MMI to normal rats C/P 35S ratios ranged from 1–5.6 but no 35S accumulation was found in PBL or thyroid lymphocytes from August strain rats in which experimental autoimmune thyroiditis had been produced.

It is concluded that there is minimal, if any, significant accumulation of MMI in lymphocytes of patients with Graves' disease. The immunosuppressive action of MMI on lymphocyte antibody production must therefore by indirect.
Somatostatinoma syndrome: does a clinical entity exist?
Authors: Stacpoole Peter W. , Kasselberg A. G. , Berelowitz Michael , Chey William Y.
Published: December 2008

We report here 2 patients with somatostatinsecreting tumours and hypersomatostatinaemia. One subject, a 36 year old woman with diabetes, flushing, labile blood pressure and diarrhoea, had elevated basal plasma levels of somatostatin-like immunoreactivity (SLIR) and calcitonin. Plasma SLIR increased further following tolbutamide administration. Plasma levels of prostaglandin E2 (PGE2) and pancreatic polypeptide (PP), normal in the basal state, showed exaggerated responses to pentagastrin and secretin, respectively. Immunocytochemistry of the tumour tissue revealed cells containing somatostatin-, calcitonin-, PGE2- and PP-like immunoreactivity. The other patient, a 52 year old male, had an SLIR-secreting tumour of the proximal duodenum and elevated basal and post-tolbutamide SLIR levels but no signs or symptoms suggestive of increased SLIR production. Tumour tissue revealed cells containing somatostatin- and calcitonin-like immunoreactivity.

We conclude that patients with somatostatinomas do not always exhibit a predictable syndrome. Patients with these tumours may exhibit a range of clinical, biochemical and immunocytochemical features typical of endocrine tumours of mixed-cell origin, such that the dominant signs and symptoms associated with these neoplasms cannot readily be ascribed to overproduction of any single hormone.
Pharmacological effects of 2- and 4-methyloestradiol as a probe to test the biological importance of 2- and 4-hydroxylation of oestrogens (catecholoestrogen-formation)
Authors: Ball Peter , Emons Günter , Haupt Otto , Knuppen Rudolf
Published: December 2008

2-Methyloestradiol, 4-hydroxy-2-methyloestradiol and 4-methyloestradiol were synthesized and infused sc into long-term ovariectomized rats by means of osmotic minipumps. The effects on uterine growth and gonadotrophin release were tested and compared to oestradiol or vehicle alone. 2-Methyloestradiol and 4-hydroxy-2-methyloestradiol, steroids in which the 2-hydroxylation is selectively blocked, definitely increased uterine weight (dry and wet), decreased morning LH and increased evening LH serum levels. 4-Methyloestradiol, a compound which cannot be 4-hydroxylated in vivo, was inactive in the model used. It is assumed that 4-hydroxylation constitutes an essential step in the expression of oestrogenicity of primary oestrogens, whereas 2-hydroxylation does not.
A quantitative assay for the cytoplasmic androgen receptor using [3H]dihydrotestosterone in the presence of NAD+-nucleosidase
Authors: Moeller Hans , Oettling Günter , Fiederer Bernhard , Brügmann Gerd
Published: December 2008

In prostatic cytosol DHT1 is metabolized to 5α-androstane-3α (or β), 17α-diols with a half life of 2 h even at 4°C. Thus, [3H]DHT appears to be a poor marker for a quantitative assessment of androgen receptors (AR). Methyltrienolone (R1881) seems to be advantageous as it is not metabolized. However, because of considerable binding to progestin receptors, assays using [3H]R1881 are not specific for AR in tissues containing progestin receptors. We, therefore, developed a specific assay for AR using [3H]DHT (14 nm) as marker, where metabolism of DHT is prevented by pre-incubation with NAD+-nucleosidase.

The [3H]DHT-receptor complex is separated from free, SHBG-bound and unspecifically bound [3H]DHT by agar gel electrophoresis. The binding sites of high affinity and low capacity are characterized by suppression with unlabelled R1881 (2 μm) in a parallel assay. Under these conditions DHT and R1881 appear to have the same kinetics of association and dissociation.

Weighted non-linear regression analysis of specific binding capacity at various ligand concentrations reveals that in rat prostatic cytosol the affinity of DHT (Kd = 0.405 ± 0.0839 nm) is significantly higher (P < 0.01) than that of R1881 (Kd = 1.25 ± 0.271 nm).
Sexual precocity in a boy due to hypersecretion of LH and prolactin by a pituitary adenoma
Authors: Faggiano M. , Criscuolo T. , Perrone L. , Quarto C. , Sinisi A. A.
Published: December 2008

The paper reports on precocious puberty and galactorrhoea in a 4 8/12 year old boy. Roentgenograms of the skull showed slight lateral bulging of sella floor and pneumoencephalography indicated a pituitary adenoma with a suprasellar extension. Pre-operative study of anterior pituitary function was normal except for increased values of LH (900 mIU/ml), testosterone (2000 ng/ml) and prolactin (215 ng/ml). After removal of a chromophobe pituitary adenoma by transfrontal surgery the galactorrhoea disappeared within 10 days. Post-operative endocrine evaluation showed immediate normalization of LH, testosterone and prolactin values.
Failure to secrete immunoreactive insulin by rats fed a low protein diet
Authors: Levine Leonora S. , Wright P. G. , Marcus Fanny
Published: December 2008

Rats fed a 6% protein diet for 14 weeks showed a normal glucose tolerance but failed to release immunoreactive insulin (IRI), following iv glucose. Furthermore the isolated perfused pancreas of the rats fed the 6% protein diet secreted eleven times less IRI than the isolated pancreas prepared from the rats reared on an 18% protein diet when both were subjected to the same glucose challenge. This difference occurred despite the fact that the total IRI content of the pancreas' was not significantly different between the two groups. In the protein-malnourished rats it is suggested that the normal glucose tolerance response, despite the failure to release a concommitant amount of IRI, may indicate increased sensitivity to IRI or may be due to the secretion in these animals of a biologically active insulin, which shows no immunological cross-reactivity with pancreatic insulin. Alternately there may be increased peripheral glucose utilisation in the low protein rats.
Evidence for cleavage of [26-14C]cholesterol side-chain by human foetal membranes in vitro
Authors: Gunasegaram R. , Loganath A. , Peh K. L. , Ng S. C. , Karim S. M. M. , Ratnam S. S.
Published: December 2008

With a view to establish the hitherto undescribed role of cholesterol in foetal-membranous steroidogenesis, homogenates of term chorion pars reflexa and amnion pars reflexa and pars placentaris collected from 6 women after spontaneous labour at term (38 to 41 weeks gestation) were incubated with [26-14C]cholesterol. Using reverse-isotope dilution analysis, [14C]isocaproic acid was isolated and characterized. This conversion constitutes strong evidence that C-20, 22-desmolase activity, normally present in the adrenal, gonadal and placental tissues, is present in the homogenates of both membranes. The efficiency of the enzymic conversion suggests that the chorion possesses a more active desmolase system compared to that of the amnion.
Serum non-protein bound percentage and distribution of the progestin ST-1435: no effect of ST-1435 treatment on plasma SHBG and CBG binding capacities
Authors: Lähteenmäki Pertti L. A. , Hammond Geoffrey L. , Luukkainen Tapani
Published: December 2008

The non-protein bound percentage of ST-1435 was measured by centrifugal ultrafiltration-dialysis in undiluted female serum at 37°C. It was found that as much as 13% of ST-1435 in serum is not bound to proteins. The results also show that the affinities of SHBG and CBG of ST-1435 are very low and that SHBG and CBG do not bind ST-1435 under physiological conditions in serum. We suggest that ST-1435 is bound mainly to serum albumin, and that the binding to that accounts for more than 87% of total serum ST-1435 concentrations. During the treatment period of 3 months, no change in SHBG or CBG binding levels was observed when ST-1435 was administered parenterally.

The lack of any interaction between ST-1435 and high affinity serum steroid binding proteins, and the very high percentage of non-protein bound ST-1435 in serum, probably explain its extremely high biological potency at the hypothalamic-pituitary level, when compared for example with d-norgestrel. For the same reason, practically all the ST-1435 in hepatic portal blood is probably taken-up and very rapidly metabolised by the liver. This may explain why oral administration of ST-1435 results in low and inadequate plasma concentrations for contraceptive purposes, while alternative parenteral routes of administration result in relatively much higher serum concentrations of the steroid. Finally, because ST-1435 does not bind to SHBG and CBG under physiological conditions, and does not change plasma SHBG and CBG binding capacities, ST-1435 treatment will not indirectly alter the amounts of endogeneous sex steroid hormones or their distribution in plasma. Therefore, side effects such as acne or hirsutism are unlikely to develop as a result of sustained administration of this potent progestin.
Regulation of immunity in rats by lactogenic and growth hormones
Authors: Nagy Eva , Berczi Istvan , Friesen Henry G.
Published: December 2008

Antibody formation to sheep red blood cells and the development of contact dermatitis in response to dinitrochlorobenzene are impaired in hypophysectomized (Hypo-X) rats. Rat prolactin, rat growth hormone, bovine prolactin, bovine growth hormone, human placental lactogen and human growth hormone all restored the immunological competence of Hypo-X animals. The possible mechanism of action of these hormones on immune reactions is discussed.