bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic treatment by the calcium channel blocker ± PN 200-110 in the rat counteracts the stimulations of pituitary weight, prolactin release and pituitary C-kinase activity induced by a chronic estradiol treatment, in vivo
Authors: Touraine Ph. , Birman P. , Bai-Grenier F. , Dubray C. , Peillon F. , Joubert(Bression) D.
Published: December 2008

In order to investigate whether a calcium channel blocker could modulate the protein kinase C activity in normal and estradiol pretreated rat pituitary, female Wistar rats were treated or not (controls) with ± PN 200-110 (3 mg · kg−1 · day−1, sc) for 8 days or with estradiol cervical implants for 8 or 15 days, alone or in combination with PN 200-110 the last 8 days. Estradiol treatment induced a significant increase in plasma prolactin levels and pituitary weight. PN 200-110 administered to normal rats did not modify these parameters, whereas it reduced the effects of the 15 days estradiol treatment on prolactin levels (53.1 ± 4.9 vs 95.0 ±9.1 μg/l, p<0.0001) and pituitary weight (19.9 ± 0.4 vs 23.0 ± 0.6 mg, p <0.001), to values statistically comparable to those measured after 8 days of estradiol treatment. PN 200-110 alone did not induce any change in protein kinase C activity as compared with controls. In contrast, PN 200-110 treatment significantly counteracted the large increase in soluble activity and the decrease in the particulate one induced by estradiol between day 8 and day 15. We conclude that PN 200-110 opposed the stimulatory effects of chronic in vivo estradiol treatment on plasma prolactin levels and pituitary weight and that this regulation was related to a concomitant modulation of the protein kinase C activity.
Neuroendocrinological effects of ketoconazole in rats
Authors: Irsy Gabor , Koranyi Lajos
Published: December 2008

The effect of ketoconazole on steroid synthesis was studied in intact (sham-operated) and castrated male and ovariectomized female rats. Rats were given 25 mg/kg ketoconazole twice a day im for 5 days. The influence of ketoconazole was also investigated on hormone release altered by GnRH, estradiol and haloperidol. The following hormones were measured: serum LH, PRL, testosterone, corticosterone, 17-OH-progesterone, estradiol, and dopamine content of the tubero-infundibular area. Ketoconazole treatment resulted in a significant decrease of testerone level (from 7.93 ± 1.99 to 3.83 ± 0.94 nmol/l), whereas LH, PRL, corticosterone and 17-OH-progesterone remained unchanged in the male rat. The effect of castration on LH level was reduced by ketoconazole in male (from 590 ± 35 to 390 ± 25 μg/l) and female rats (from 468 ± 22 to 346 ± 39 μg/l), but the GnRH-stimulated LH release in castrated and ovariectomized animals was unchanged. The suppressive action of estradiol on LH in ovariectomized rats was enhanced (from 160 ± 41 to 64.6 ± 12.9 μg/l), and its priming effect on PRL release was diminished by ketoconazole (from 598 ± 81 to 281 ± 66 μg/l). Ketoconazole failed to modify the tubero-infundibular dopamine content and haloperidol-induced PRL release. It can be assumed that in addition to its inhibitory role of steroid biosynthesis ketoconazole has an influence on central mechanisms underlying LH and PRL release.
Radioiodine therapy in voluminous multinodular non-toxic goitre
Authors: Vereist Jean , Bonnyns Marc , Glinoer Daniel
Published: December 2008

Large doses of radioiodione were administered since 1969 to 15 euthyroid patients with compressive voluminous goitres. A decrease in goitre size was observed in all patients (between 15 and 63%, average 39%). Maximal effect on goitre size was attained rapidly, partially already after less than one year and was almost maximal after 24 to 30 months. No significant local adverse reactions were observed; no patient required steroid administration. Hypothyroidism followed radioiodine administration in 30% of the patients after 2 years; after 8 years, all those who had survived were hypothyroid, requiring substitution therapy. In all patients there was a marked improvement in compression symptoms. The use of radioactive iodine therapy constitutes an alternative to surgery in selected patients with large compressive goitres in whom surgery is contraindicated because of age or other medical conditions.
Effects of a gonadotropin-releasing hormone agonist on progesterone formation in cultured human granulosa cells
Authors: Olsson Jan-Henrik , Åkesson Ingegerd , Hillensjö Torbjörn
Published: December 2008

Human granulosa cells from follicles of natural cycles (13 women) in mid- or late follicular phase were cultured in modified Medium-199. Human luteinizing hormone (100 μg/l), follicle-stimulating hormone (100 μg/l) and gonadotropin-releasing hormone agonist (GnRHa) (10−12 to 10−6 mol/l) alone or in combination were added to the culture medium. Medium content of progesterone was analysed. In granulosa cells obtained in the mid-follicular phase, the basal progesterone formation averaged 0.5 pg · cell−1 · (48 h)−1· FSH caused a 3-fold stimulation. GnRHa (10−6 mol/l) had a variable influence on the basal progesterone formation, whereas it consistently inhibited (40–50%) the FSH response. In granulosa cells from late follicular phase basal progesterone formation averaged 5 pg · cell−1 ·(48 h)−1 and was stimulated 3-to 6-fold by LH. GnRHa (10−6 mol/l) stimulated the basal progesterone formation and caused a tended to potentiate the LH response on progesterone formation. It is concluded that GnRHa at relatively high concentrations exerts direct effects on gonadotropin-stimulated progesterone formation of human granulosa cells and that these effects are different (inhibitory or stimulatory) dependent on the degree of follicular maturation, and/or type of gonadotropin used.
Pharmacokinetics and pharmacodynamics of testosterone enanthate and dihydrotestosterone enanthate in non-human primates
Authors: Weinbauer Gerhard F. , Jackwerth Bettina , Yoon Yong-Dal , Behre Hermann M. , Yeung Ching-Hei , Nieschlag Eberhard
Published: December 2008

The pharmacokinetics and pharmacodynamics of testosterone enanthate and dihydrotestosteroneenanthate were compared in orchidectomized cynomolgus monkeys (Macaca fascicularis) and in intact GnRH agonist-suppressed rhesus monkeys (Macaca mulatta). Following a single im injection of 32.8 mg testosterone enanthate or 32.7 mg dihydrotestosteroneenanthate, i.e. 23.6 mg of pure steroid, in the orchidectomized cynomolgus monkeys, serum testosterone and dihydrotestosterone levels rose to 400 and 800% of baseline, respectively, within 24 h. Androgen levels remained in that range for 3-5 days followed by a continuous decline until baseline values were attained after 4-5 weeks. The areas under the testosterone- and dihydrotestosterone-curves did not differ significantly 2290±340 (dihydrotestosterone-enanthate) vs 2920±485 (testosteroneenanthate) suggesting that similar amounts of steroid had been released from the respective ester preparation. Mean half-life estimates of the terminal elimination phase were 4 and 7 days for testosterone-enanthate and dihydrotestosterone-enanthate, respectively. In a second experiment rhesus monkeys received, at 4-weekly intervals, sc implantation of a biodegradable polylactic:polyglycolide rod loaded with the GnRH agonist buserelin. The last injection was given during week 20. GnRH agonist treatment suppressed serum bioactive LH, testosterone and dihydrotestosterone levels, testicular size, sperm production, and seminal carnitine content. The ejaculatory response to electrostimulation and the masturbatory behaviour were abolished. Testosterone or dihydrotestosterone injections at the same doses as above were given in week 10, 14, 17 and 20 of GnRH agonist treatment. Serum testosterone and dihydrotestosterone levels were stimulated 9- and 4-fold, respectively. Mean half-life estimates for testosterone-enanthate and dihydrotestosterone were 5 and 7 days, respectively. Both ester preparations completely restored the ejaculatory response, ejaculate size, masturbatory behaviour, and seminal carnitine levels. In conclusion, androgen substitution with dihydrotestosterone-enanthate, in equivalent doses, is as effective as testosterone-enanthate in restoring reproductive functions in hypogonadal monkeys.
Polyglandular autoimmune syndrome Type II in patients with idiopathic Addison's disease
Authors: Papadopoulos Konstantin I. , Hallengren Bengt
Published: December 2008

The frequency of polyglandular autoimmune syndrome Type II, (idiopathic or autoimmune Addison's disease associated with autoimmune thyroid disease, and/or insulin-dependent diabetes mellitus), was retrospectively investigated in 44 patients (26 females and 18 males) with idiopathic Addison's disease (median age at onset 32.5 years, range 8–62; median observation time 17 years, range 0.5–41) evaluated between 1966 and 1988 in the Department of Endocrinology, General Hospital, Malmö. Twenty-two patients (16 females and 6 males) fulfilled the criteria for polyglandular autoimmune syndrome Type II and of these 16 had autoimmune thyroid disease and 9 insulin-dependent diabetes mellitus. In 7 of 9 patients insulin-dependent diabetes mellitus developed prior to Addison's disease, whereas autoimmune thyroid disease was diagnosed before as well as after Addison's disease and with a similar age distribution as Addison's disease. In conclusion, the present study indicates that polyglandular autoimmune syndrome Type II occurs in about 50% of patients with idiopathic Addison's disease and that autoimmune thyroid disease is more common than insulin-dependent diabetes mellitus in these patients. The present study also indicates that insulin-dependent diabetes mellitus precedes Addison's disease in a majority of these patients and usually develops at a young age, whereas autoimmune thyroid disease precedes as well as succeeds Addison's disease and occurs at all ages in these patients.
Influence of neurohypophysectomy on the renal actions of aldosterone in the adrenalectomized rat
Authors: Musabayane Cephas T. , Brimble Martyn J. , Balment Richard J. , Kelly Lesley P.
Published: December 2008

The influence of aldosterone administration on urine flow, Na+ and K+ excretion was examined in hypotonic saline infused, Inactin® anesthetised rats following removal of the adrenals or adrenals and posterior pituitary. Plasma adrenal steroid levels were considerably depressed but still detectable 10-14 days after adrenalectomy. Removal of the posterior pituitary markedly reduced Na+ excretion in adrenalectomized animals implying that Na+ retention following neurohypophysectomy is not dependent on adrenal gland function. In adrenalectomized rats aldosterone administration at 42 pmol/min reduced Na+ excretion and urine flow without significantly changing K+ excretion, though plasma K+ was reduced. In adrenalectomized/neurohypophysectomized rats aldosterone further reduced the already low rate of Na+ excretion and increased K+ excretion, though there was no observable effect on urine flow. The results obtained indicate that the Na+-retaining actions of aldosterone are largely independent of posterior pituitary influence. The K+-losing action of aldosterone was, however, only observed in animals in which the posterior pituitary was absent.
Urinary excretion of [D-Ser(t-Bu)6, Des-Gly10]GnRH ethylamide (buserelin) during therapy of central precocious puberty: a multicentre study
Authors: Sizonenko Pierre C. , Reznik Yves , Aubert Michel L.
Published: December 2008

In order to compare the clinical effects of buserelin on central precocious puberty to its excretion in urine, as a parameter of metabolism or compliance, we have studied 52 patients treated either sc or intranasally. In girls with good control, urinary buserelin excretion represented 0.5 ± 0.1% of the daily intranasal dose vs 12.5 ± 2.3% of the daily sc dose. In boys, it represented 0.8 ± 0.2 and 9.9 ± 2.7%, respectively. In the sc treated group, 3 patients (2 girls and 1 boy) with poor control who exhibited excretion levels similar to those with good control were classified as resistant to therapy. Clinical control was poor in 4 intranasally treated girls: 2 had low excretion values suggesting poor compliance or failure of absorption by the nasal mucosa, and 2 appeared resistant to therapy, as urinary excretion levels of buserelin were similar to those of well-controlled patients. In addition, these data suggest that the small amount of buserelin absorbed by the nasal mucosa, as expressed by urinary excretion, is sufficient to desensitize the pituitary gonadotropes without any significant first-pass effect in the systemic circulation. This may explain the clinical effectiveness of the intranasal route for administration of small hormonal peptides acting on the pituitary gland.
Sex steroids modulate the pituitary parameters involved in the regulation of TSH secretion in the rat
Authors: Donda Alena , Reymond Frédéric , Rey François , Lemarchand-Béraud Thérèse
Published: December 2008

The sex-related differences observed in the regulation of TSH secretion was further investigated by determination of the densities of T3 nuclear and TRH membrane receptors as well as the activity of 5'-deiodinase (5'D) in the anterior pituitary gland of adult male and female rats. The respective modulatory roles of androgens and estrogens on these parameters were evaluated by similar determinations carried out in castrated and in estrogen-treated male rats. The density of pituitary T3 and TRH receptors and the activity of 5'D type II were significantly greater in the female than in the male rats. The E2-treated male rats disclosed a female profile, viz. also greater densities of T3 and TRH receptors when compared with control male rats (2.3 ± 0.2 vs 1.8 ± 0.2 fmol T3/mg gland and 9.4 ± 0.8 vs 6.0 ± 0.8 fmol TRH/mg gland, mean ± sem), whereas no changes were found in the castrated rats. The E2-treated rats and the castrated rats exhibited an increased pituitary activity of 5'D, type II (0.87 ± 0.10 and 0.66 ± 0.05, respectively, vs control 0.34 ± 0.07 pmol rT3 · h−1 · (mg protein)−1), suggestive of a stimulatory effect of E2 and of an inhibitory effect of androgens on this parameter. In contrast, no differences in hepatic 5'D were found between all groups, illustrating the well-known tissue-specific regulation of 5'D. These results demonstrate that the sex difference in the density of pituitary T3 and TRH receptors and the activity of 5'D in the adult rat is mainly due to a modulatory effect of estrogens, which may be responsible for the sex-dependent regulation of TSH secretion.
Triiodothyronine stimulates 2-deoxy-D-glucose uptake by organ cultured embryonic chick small intestine
Authors: Prager Christiane , Cross Heide S. , Peterlik Meinrad
Published: December 2008

The possible contribution of increased D-glucose absorption from the intestine to the impairment of oral glucose tolerance in hyperthyroidism was evaluated by investigating the influence of T3 on different pathways of D-glucose transport, utilizing an organ culture system of embryonic chick small intestinal explants. T3, when present in the culture medium at a concentration between 10−10-10−8 mol/l, had no effect on uptake of α-methyl-D-glucoside, but stimulated uptake of 2-deoxy-D-glucose by the intestinal epithelium in a dose-dependent fashion. T3 thereby enhanced the maximal velocity of a saturable, cytochalasin B-sensitive but phloretin-insensitive 2-deoxy-D-glucose transport system with an apparent Km of 7 mmol/l. The combined data are consistent with the assumption that T3 can enhance D-glucose entry into the intestinal epithelium through stimulationof a low-affinity transport system at the brush-border membrane of enterocytes. Our findings provide a basis for the explanation of adaptive modulation of intestinal glucose absorption in hyperthyroidism.
A monthly cycle in the adrenocortical function during third trimester pregnancy
Authors: Paaby Per O. , Nielsen Aage , Raffn Kjeld
Published: December 2008

Eleven healthy women were examined three times a week during the third trimester. The possibility of monthly cyclical changes in the serum concentrations of cortisol, placental hCG and fetoplacental estradiol was tested because of previous findings of highly significant monthly cycles in aldosterone and progesterone. A semi-parametric statistical model was used and a highly significant monthly cycle in serum cortisol was found, whereas the amplitude for a cycle in hCG was barely significant and non-significant for estradiol. The previous findings of monthly cycles in aldosterone and progesterone, using a parametric multivariate model, were retested by the semiparametric method employed for the present publication. The findings of highly significant cycles in aldosterone and progesterone were corroborated. We think that the results indicate the existence of an adrenocortical cycle. We think that the monthly ovarian cycle in the non-pregnant state is paralleled by an adrenocortical cycle, where changes in aldosterone are "linked" with changes in progesterone and changes in cortisol with changes in estrogens. During pregnancy the adrenocortical cycle persists, probably controlled by the maternal hypothalamus. The physiological background for this monthly endocrine cycle during pregnancy is enigmatic.
Thyrotropin results in euthyroid patients with a past history of hyperthyroidism
Authors: Brownlie Bevan E. W. , Legge Helen M.
Published: December 2008

Sensitive TSH levels were measured in 93 euthyroid patients with a past history of hyperthyroidism. Subnormal TSH values were found in 18 out of 75 (24%) patients previously treated with a course of antithyroid drugs, and in 3 out of 18 (17%) post-thyroidectomy patients. These subnormal TSH results are a limitation to the general applicationof the TSH-first strategy. Twelve months follow-up showed that subnormal TSH values are associated with increased risk of relapse in the antithyroid drug treated group (p<0.001). Longer follow-up varies in duration and some late relapses have occurred in drug treated patients with normal baseline TSH levels. To date relapses have occurred in 3 out of 56 normal TSH patients compared with in 6 out of 16 suppressed TSH patients; no thyroidectomy patients have relapsed. Prospective studies are needed to confirm the predictive value of sensitive TSH measurements.
The synthesis and release of gonadotropins in response to gonadotropin-releasing hormone of the rat anterior pituitary gland during weight reduction
Authors: Kotsuji Fumikazu , Aso Takeshi , Kamitani Naoyuki , Tominaga Toshiro
Published: December 2008

It is well recognized that weight reduction produces the suppression of serum LH but not FSH level in rodents. In order to clarify the mechanism by which the discrepancy between LH and FSH levels is brought about, the influence of weight loss on the pituitary function was explored using female rats. The changes of the pituitary response to GnRH and the basal secretion of gonadotropins with progressive weight loss were investigated by in vitro short-term incubation of the pituitary gland after prolonged weight loss in female Wistar rats. On the first day of diestrous and until day 14 of the diet, GnRH induced LH and FSH release from the pituitary and a decrease in pituitary content of them, but the total amount of gonadotropin in culture medium and pituitary tissue was not affected. On day 30 of the diet, the decrease in pituitary content disappeared. On day 60 LH release disappeared, whereas pituitary FSH and the total amount of gonadotropins were increased by GnRH. Non-stimulated FSH but not LH secretion per mg of pituitary was augmented during dieting. The data indicate that pituitary responsiveness to GnRH and non-stimulated FSH release were modified by weight loss: the LH-releasing action of GmRH was diminished, the gonadotropin-synthesizing action of GnRH was augmented, and non-stimulated FSH release was increased.
Further evidence of an opposite effect of dorsal and median raphe nuclei on the proestrous surge of LH
Authors: Morello H. , Caligaris L. , Haymal B. , Taleisnik S.
Published: December 2008

The effect of stimulation or lesions of either the dorsal or the median raphe nucleus on the proestrous surge of LH and on ovulation was studied in rats kept under constant illumination. Electrochemical stimulation (anodic DC of 100 μA during 30 sec) was applied at noon on the day of proestrus through chronically implanted electrodes. Lesions of the raphe nuclei were made by passing a cathodic current of 1 mA for 20 sec through nichrome electrodes stereotaxically implanted. Blood samples from freely behaving rats were obtained hourly through cannulae inserted into the jugular vein. Rats under constant light from diestrous day 1 or diestrous day 2 showed a delay in the onset of the LH surge of the next proestrus. Stimulation applied into the median raphe nucleus inhibited proestrous LH release and blocked ovulation, whereas stimulation of the dorsal raphe nucleus resulted in enhanced LH release in rats under constant light from diestrous day 2 but not from diestrous day 1. In turn, in rats bearing lesions in the dorsal raphe nucleus LH surges were decreased and ovulation was blocked, but rats with lesions in the median raphe nucleus exhibited enhanced LH release. It is concluded that the dorsal and the median raphe nuclei exert opposite effects on the proestrous surge of LH and on ovulation.
An update on the frequency of nonclassic deficiency of adrenal 21-hydroxylase in the Yugoslav population
Authors: Dumić Miro , Brkljačić Ljerka , Speiser Phyllis W. , Wood Elizabeth , Crawford Christopher , Plavšić Vesna , Baničeviác Miloš , Radmanović Slobodan , Radica Ana , Kaštelan Andrija , New Maria I.
Published: December 2008

Nonclassic steroid 21-hydroxylase deficiency is an attenuated adrenal enzyme defect that is commonly the basis of hyperandrogenic syndromes. Inherited as an autosomal recessive trait, it is known to occur with high frequency in the general population and with increased frequency in a number of ethnic groups, including the Yugoslav population. Following expansion of the original data on 21 families in Croatia to a total of 49 Croatian and Serbian families, we establish that this enzymatic disorder is increased in this Slavic population and provide an updated estimate for the gene frequency of 0.092 (0.035-0.149). Also in keeping with earlier reports, we continue to note the absence of association between nonclassic 21-hydroxylase deficiency occurring among Yugoslavs and HLA-B14;DR1.
Vitamin D metabolism in osteoporotic women during treatment with estrogen, an anabolic steroid, or calcitonin
Authors: Hartwell Dorthe , Hassager Christian , Overgaard Kirsten , Riis Bente Juel , Pødenphant Jan , Christiansen Claus
Published: December 2008

We assessed the effects of a continuous oral combination of estradiol and norethisterone acetate, nandrolone decanoate, or salmon calcitonin on the vitamin D endocrine system. One hundred and nineteen postmenopausal women, aged 55-75 years, with at least one osteoporotic fracture, were randomly allocated to one year of treatment with estradiol and norethisterone acetate, nandrolone decanoate, or calcitonin, all drugs with a beneficial effect on bone. All three trials were double-blind and placebo-controlled; 104 women (87%) completed the study. We measured the total serum concentration of 1,25-dihydroxyvitamin D (1,25(OH)2D) and vitamin D-binding protein, and estimated the free 1,25(OH)2D index and the "24-hydroxylase activity" initially, and at 6 and 12 months. Furthermore, the 24-h urinary excretions of calcium, phosphate, and adenosine 3'-5'-cyclic monophosphate were assessed initially and at 12 months. The serum concentration of vitamin D-binding protein and 1,25(OH)2D increased transiently during estradiol and norethisterone acetate treatment and vitamin D-binding protein decreased transiently during nandrolone decanoate treatment. None of the other parameters were significantly affected by any of the three treatments. The risk of type II errors was below 10 per cent for all vitamin D measurements. We conclude that the vitamin D metabolites are unlikely to be of major importance for the mechanism by which these drugs exert their positive skeletal effects.
Factors influencing the outcome of thyrostatic drug therapy in Graves' disease
Authors: Winsa Brita , Dahlberg Per Anders , Jansson Rolf , Ågren Hans , Karlsson F. Anders
Published: December 2008

In patients with Graves' disease, thyrostatic drug treatment may induce definitive remission without the need of more aggressive measures such as surgery or radioiodine. Following drug therapy, however, relapses often occur. In the present study, a multivariate analysis of pretreatment variables was performed, in order to identify individuals running a high risk of an unfavourable outcome of thyrostatic drug therapy. We studied 109 consecutive patients with a mean age of 38 years, range 20–70, over a mean follow-up period of 5.3 years after cessation of therapy. The analysis showed that goitre size, age, thyroid hormone levels, HLA-DR 3 haplotype, and TSH receptor antibody levels were of prognostic significance, whereas HLA-B8 haplotype, a lymphocytic infiltrate at fine needle biopsy, thyroglobulin, and microsomal antibodies had no such value. In particular, patients characterized by young age, large goitre and high hormone values were found to be associated with an unfavourable course.
Secretion of alpha and TSH-beta subunits in patients with acromegaly: an in vivo study
Authors: Assadian Hossein , Shimatsu Akira , Koshiyama Hiroyuki , Hattori Naoki , Ishikawa Yasuhiro , Tanoh Tsutomu , Imura Hiroo
Published: December 2008

Plasma alpha and TSH-beta subunit responses to iv administration of GHRH were examined in 19 patients with active acromegaly. In 4 patients (21%), plasma alpha subunit levels were increased over 50% of basal levels after administration of GHRH, whereas plasma TSH-beta subunit levels were increased in response to GHRH in another 5 patients (26%). No patient showed simultaneous increases of alpha and beta subunits. After successful surgery, alpha and TSH-beta subunits did not respond to GHRH. These findings support the idea that some pituitary adenomas in acromegaly co-secrete GH and either alpha subunit or TSH-beta subunit.
THE RESPONSE OF THE ADRENAL CORTEX TO PSYCHIC STRESS AFTER MEPROBAMATE TREATMENT
Authors: Mäkelä S. , Näätänen E. , Rinne U. K.
Published: December 2008

A study has been made of the effect of acute as well as chronic meprobamate treatment on the adrenal ascorbic acid depletion caused by psychic stress, and of the effect of meprobamate treatment on the adrenal cortex. The results obtained in this work indicate that meprobamate is able under acute experimental conditions to inhibit the ascorbic acid depletion caused by psychic stress although in the meprobamate plus psychic stress group the adrenal ascorbic acid quantity was highly significantly less than in the controls. During chronic treatment, again, adaptation occurs, causing the blocking effect of meprobamate to cease after 11 to 14 days' treatment. It was found, on the other hand, that meprobamate treatment alone stimulates the adrenal cortex in intact as well as unilaterally adrenalectomized animals. The possible mechanisms of action are discussed.
DETERMINATION OF INDIVIDUAL ADRENOCORTICAL STEROIDS IN URINE OF PREGNANT WOMEN
Authors: Johnson David F. , Francois Daniel , Heftmann Erich
Published: December 2008

The urinary excretion of individual adrenocortical steroids has been studied throughout the course of normal pregnancy and in complications of pregnancy, including toxaemia, diabetes and rheumatoid arthritis. The pattern of U. V. absorbing and reducing compounds was qualitatively the same for all urines. Of the reducing steroids, three have been identified as allopregnanetetrolone, pregnanetrioldione and pregnanetetrolone. The quantitative changes of the individual compounds in the course of normal pregnancy and in complications of pregnancy are discussed.
EFFECT OF CORTISONE ON GROWTH AND ON 35S UPTAKE BY MUCOPOLYSACCHARIDES OF TRANSPLANTED OSTEOSARCOMA IN RATS
Authors: Kowalewski K.
Published: December 2008

Cortisone significantly inhibited the growth of Noble's transplanted osteosarcoma in rats. Cortisone also inhibited the uptake of 35S by sulphated mucopolysaccharides of tumours. This observation is in agreement with the known effects of glucocorticoids on certain elements of connective tissue.
STUDIES ON URINARY GONADOTROPHINS
Authors: Johnsen Svend G. , Hamburger Christian
Published: December 2008

The gonadotrophic activities of the International Reference Preparation for Human Menopausal Gonadotrophin (HMG 24) and of its predecessor, the unofficial reference preparation (HMG 20A), were assayed against 7 other preparations of postmenopausal urines extracted and purified by different methods. The end-points of assay were the dose-response curves for mean uterine and ovarian weights in immature rats.

A marked qualitative difference was found between the 7 different extracts on the one hand and the reference preparations on the other.

This difference is tentatively assumed to be caused by a relatively greater loss of follicle stimulating hormone than of luteinizing hormone in the procedures used for the extraction and purification of HMG 24 and HMG 20A.

It is concluded that HMG 24 and HMG 20A are unsuitable as reference preparations for human menopausal gonadotrophin and for hypophyseal gonadotrophins in general.
STUDIES ON THE CORTICOTROPHIN RELEASING ACTIVITY OF SYNTHETIC OXYTOCIN
Authors: Rinne U. K. , Kivalo E. , Lahtinen K.
Published: December 2008

The ACTH-releasing activity of synthetic oxytocin has been investigated in male rats, using adrenal ascorbic acid depletion as an indication of ACTH release. In acute experimental conditions synthetic oxytocin caused a highly significant adrenal ascorbic acid depletion in normal animals, as compared both to intact controls and to controls injected with physiological sodium chloride solution. It did not however, produce any adrenal ascorbic acid depletion in animals blocked by means of prednisolone. Administered as daily injections, synthetic oxytocin no longer caused any significant adrenal ascorbic acid depletion after six to nine days of treatment. It has been concluded that the ACTH-releasing activity of synthetic oxytocin is non-specific and thus is not the hypothalamic neurohumoral substance causing ACTH release from the anterior pituitary gland. The nature of this substance has been discussed in the light of previous results and of those obtained in the present investigations.
ALTERATION IN HORMONAL ACTIVITY RESULTING FROM CHEMICAL TREATMENT OF BEEF GROWTH HORMONE
Authors: Sonenberg Martin , Money William L.
Published: December 2008

The effect of various reagents, which produce protein derivatives, on the biological activity of growth hormone has been studied. Various conditions which affect growth hormone stability have also been investigated. In general, it has been found that reaction of growth hormone with phenylisocyanate, nitrous acid or concentrated sulfuric acid, under the conditions specified, destroyed the biological activity. Reaction of growth hormone with thioglycolic acid, iodine, or acid methanol yielded growth hormone derivatives which were active or inactive, depending on the reaction conditions. Reaction with acid ethanol, formaldehyde, cysteine, sodium bisulfite, diisopropylfluorophosphate, urea or bromine had no effect on the growth-promoting activity of these preparations. Growth hormone was found to be rather stable in dilute and glacial acetic acid except when heated to a temperature of 94° C. The implications of these findings are discussed.

None of the growth hormone derivatives obtained in this study was able to inhibit the growth-promoting response induced by unmodified growth hormone preparations.
PITUITARY REGULATION OF THYROID ACTIVITY
Authors: Christensen L. Korsgaard
Published: December 2008

Under normal conditions the thyroid function is mainly controlled by the content of thyroid hormone in plasma. If the level is too low, this acts as a stimulus for the pituitary production of thyrotrophic hormone. If it is too high, the opposite effect prevails. Administration of salicylate or dinitrophenol influences the thyroid function in a way which appears to contradict the existence of a regulating mechanism of this kind. However, evidence is presented which is consistent with the view that it is not the total content of thyroid hormone in the plasma, but its content of free, non-protein-bound thyroxine that regulates the pituitary effect on the thyroid.
REPRODUCTIVE PERFORMANCE IN THE ALLOXAN DIABETIC FEMALE RAT
Authors: Lawrence A. M. , Contopoulos A. N.
Published: December 2008

Sexual maturity was delayed in prepuberal rats rendered diabetic by alloxan; this could not be attributed to inanition alone. Mature rats rendered diabetic ceased to have cyclic oestrous periods, and the ovaries, uterus, and vagina involuted. Insulin restored the oestrous cycles and fertility to normal in the sexually mature alloxan diabetic rats. When the insulin was withdrawn after breeding some diabetic rats successfully delivered viable litters. In the majority, however, foetal death and resorption occurred about the 10th day of gestation. The lactational performances in alloxan-diabetic rats was variable and subnormal. This variability in reproductive performance probably accounts for the lack of agreement in the literature. No obvious correlation existed between the degree of hyperglycaemia in rats which maintained pregnancy and in those which failed to deliver viable young.
TESTOSTERONE AND THE GROWTH OF MAMMARY GLANDS AND OTHER TISSUES OF HYPOPHYSECTOMIZED RATS TREATED WITH THYROXINE, INSULIN AND CORTISONE
Authors: Donovan B. T. , Jacobsohn Dora
Published: December 2008

The reaction of the mammary glands to testosterone propionate was studied in gonadectomized, hypophysectomized rats treated with thyroxine, insulin and cortisone in various combinations. The weight and length of the body and the weight of the liver, heart ventricles, adrenal glands, seminal vesicles and ventral prostate was also recorded.

Growth of alveolar lobules, such as produced by injections of testosterone into rats with intact pituitary gland did not occur in any of the 3 groups of hypophysectomized rats studied, that is, neither after treatment with testosterone and 1) thyroxine and cortisone, 2) insulin and cortisone, nor 3) thyroxine, insulin and cortisone. An abnormal elongation of side buds and a hyperplasia and proliferation of ductal epithelium did occur and was most prominent in the group receiving insulin and cortisone.

A marked increase in body length, as well as in body weight, was observed in the group treated with testosterone, thyroxine, insulin and cortisone. The results are discussed with regard to the enhanced growth response to ovarian hormones observed in this laboratory under similar conditions.
ACTION OF ENZYME DIGESTED PITUITARY GLANDS OF THE SKIPPER-FROG ON THE OVULATION OF THE SAME
Authors: Ramaswami L. S. , Lakshman A. B.
Published: December 2008

By using enzymes, the gonadotrophic factors in the skipper-frog pituitary glands have been selectively inactivated or destroyed. By incubating a known number of pituitary gland homogenate with ptyalin in a constant temperature bath for 5–6 h the follicle-stimulating factor is inactivated; with trypsin or pepsin, the luteinizing factor is inactivated. Bioassay on gravid skipper-frogs indicate that the ptyalin digested homogenate brings about profuse spawning while the trypsin or pepsin digested homogenates do not. When a combination of ptyalin digested and trypsin digested homogenates is injected into fresh gravid skipper-frogs, poor spawning is brought about. These experiments show that the luteinizing factor alone brings about more profuse spawning than when it is combined with the follicle-stimulating factor. It is likely, therefore, that in the lower vertebrates the luteinizing factor of the pituitary gland plays a more predominant role. The exact proportions in which the different dosages for the control and test animals are administered are also tabulated.
STUDIES ON OESTROGENS IN CATTLE
Authors: Velle Weiert , Erichsen Stian
Published: December 2008

A review is given of previous in vitro investigations on oestrogen metabolism. In the present investigation use has been made of the tissue culture technique, whereby possible blood or serum effects on oestrogen transformations could be excluded. The conversion products were characterized by chemical methods.

In the presence of bovine kidney cells grown on a medium of known composition, the following conversions were recorded: Oestrone to oestradiol-17β, oestradiol-17β to oestrone, oestradiol-17α to oestrone. Control incubations of the hormones with medium only showed that the transformations must be due to the presence of the living cells. The rate of conversion to oestrone was markedly higher for oestradiol-17β than for oestradiol-17α. As previous in vivo experiments have shown oestradiol-17α to be an important end product in the bovine, following injections of both oestrone and oestradiol-17β, the free interconvertibility of oestrone and oestradiol-17β demonstrated in the present investigation becomes significant. The findings are discussed in relation to recent observations on hormoneenzyme interrelations.
FLUORIMETRIC DETERMINATION OF FREE PLASMA 11-HYDROXYCORTICOSTEROIDS IN MAN
Authors: De Moor Pieter , Steeno Omer , Raskin Monique , Hendrikx Achiel
Published: December 2008

A fluorimetric method for the determination of the free 11-hydroxycorticosteroids (cortisol and corticosterone) in human plasma has been described. Using a routine fluorimeter, 1–2 ml plasma samples are needed for a valid determination. The procedure is reliable as judged by the criteria of Borth (1957). One single trained technician can perform 40–50 determinations a day. Background fluorescence equivalent to about 3 μg % hydrocortisone is found; this background fluorescence does not appear to be related to plasma cholesterol. The method is designed primarily to study the dynamics of adrenocortical function in a given individual and can be of help as an emergency screening test (a determination can be done in one hour) in cases of suspected adrenocortical dysfunction.
ELIMINATION OF ENDOGENOUS CORTICOSTEROIDS IN VIVO
Authors: Bojesen Ejgil , Egense Johan
Published: December 2008

In experiments with the anaesthetized and acutely adrenalectomized cat it has been shown that the endogenous corticosteroids, cortisol and corticosterone are eliminated at the unstimulated normal level at a rate proportional to the plasma concentration. Hepatectomy prolonged the half life by a factor of about two (from 35 ± 8.6 to 79 ± 22 min) and total abdominal evisceration abolished all true elimination. Determinations of the arteriovenous difference across the portal system gave results in accordance with these results. A few experiments suggested that the intestine is responsible for the main part of the extrahepatic elimination. In experiments with the perfused isolated hindquarter preparation it was impossible to demonstrate any elimination of corticosteroids in spite of electrical stimulation or the administration of large amounts of insulin.
CONN'S SYNDROME: THE EFFECT OF AMPHENONE
Authors: Hoet Joseph J. , Molineaux Louis
Published: December 2008

A case of primary aldosteronism is described which was associated with a marked left kidney atrophy.

This patient showed hypertension, hypokalaemia, hypochloraemic alkalosis with urinary sodium and potassium loss. The inhibition of aldosterone secretion by the administration of amphenone and the associated changes in the urinary and blood electrolytes made it possible to focus attention to the mineralocorticoid secretion of the adrenal in this case, since it induced a reversion to normal of the abnormal biochemical blood picture.

The patient died suddenly of a cerebrovascular accident. At autopsy, a left adrenal adenoma, weighing 13 g, mainly containing cells resembling those of the zona glomerulosa, was found.
35S-AUTORADIOGRAPHY OF THE RETROBULBAR CONNECTIVE TISSUE AND HARDER'S GLAND IN THYROTROPHIN-STIMULATED GUINEA-PIGS
Authors: Wegelius Otto , Lamberg B.-A.
Published: December 2008

The localization of 35S-labelled sulphate in the retrobulbar connective tissue and Harder's glands of untreated and thyrotrophin stimulated guinea-pigs was autoradiographically determined. Uptake of sulphate was observed in the mast cells, in the metachromatic connective tissue ground substance, in the cells of Harder's gland, and in the secretion of the latter of untreated as well as of stimulated animals. The secretory activity seemed to be due to thyrotrophic hormone stimulation.
THE NEUTRAL 17-KETOSTEROID EXCRETION DURING THE MENSTRUAL CYCLE
Authors: Huis in 't Veld L. G.
Published: December 2008

The excretion of Zimmermann chromogens was determined during 3 menstrual cycles in a woman with regular menstruation, suffering from Addison's disease following bilateral adrenalectomy. The 3 cycles investigated were normal (ovulatory) according to the conventional criteria. The medication given (DOCA, deoxycorticosterone-trimethyl-acetate (DOCTA), cortisone) gave rise to the excretion of small quantities of pregnanediol, pregnanolones and 11-oxygenated 17-ketosteroids in the urine. The progesterone produced in the corpus luteum gave rise to urinary excretion of pregnanediol and probably pregnanolones.

The results obtained indicate that the ovarian secretion of precursors of 17-ketosteroids (17-hydroxyprogesterone and androst-4-en-3,17-dione) must be exceedingly small. No findings were obtained which indicate the existence of cyclic fluctuations in the ovarian secretion of precursors of neutral 17-ketosteroids.
COMPARISON OF THE BIOLOGICAL EFFECT OF OESTROGEN ON THE VAGINAL CYTOLOGY IN GONADAL DYSGENESIS AND AFTER OOPHORECTOMY
Authors: Hortling H. , Hiisi-Brummer Leila
Published: December 2008

The vaginal cytology was compared in cases of gonadal dysgenesis and in surgically castrated women. In the castrated women a moderate oestrogen effect was observed in the vaginal smear, but this was not as a rule seen in the smears of the patients suffering from gonadal dysgenesis. The possible cause of this discrepancy is discussed.
CROSS-OVER DESIGNS IN THE BIOASSAY OF CORTICOTROPHIN
Authors: Lyng Jørn
Published: December 2008

The relevant data from 28 subcutaneous triplet cross-over assays of corticotrophin are given.

The possible advantage of a twin cross-over design for the »in vitro« standardization of corticotrophin has been investigated, and it is concluded, that when the randomization of the adrenal tissue has been properly performed, there will be no advantage in this design.

An attempt has been made to do an »in vitro« cross-over assay of corticotrophin without mixing the glands. The efficiency of the design is shown, but it is concluded that it is not effective enough to eliminate the effect of the highly heterogeneous material.
STUDIES IN THE SUPPOSED GOITROGENOUS EFFECT OF TAP WATER IN HELSINKI
Authors: Krusius F.-E. , Peltola P.
Published: December 2008

The study reported here was performed in order to examine the tap water of Helsinki for its alleged goitrogenous effect.

In a short-term, 24-hour experiment with rats, kept on an iodine-poor diet, we noticed no inhibition of the 4-hour 131I uptake, as compared with that of animals receiving physiological saline instead of tap water. Two similar groups of rats receiving 1 and 2 mg of mercazole in redistilled water showed a distinct blockage of the 4-hour uptake, which proved the effect of this substance.

In a long-term experiment of 5 weeks' duration there was no detectable difference in the body weight, thyroid weight and the 4-hour 131I uptake when the rats receiving tap water or distilled water to which 0.45 per cent of sodium chloride was added were compared with each other. Replacement of tap water by a 10 mg per cent solution of mercazole in redistilled water enlarged the thyroid to double its normal weight and increased the 131I uptake to approximately five times that of the controls.

Thus our experiments failed to demonstrate any goitrogenous effect in the tap water of Helsinki. Changes similar to those produced by a long-term administration of mercazole, i. e. an enlargement of the thyroid and an increased thyroidal iodine uptake, have been shown to be due to milk collected from goitrous areas. The observations here reported confirm the importance of milk in the genesis of the goitre endemia of Helsinki. Attention is further called to the fact that a thyroidal enlargement combined with an increased thyroidal iodine uptake cannot always be taken as a sign of iodine deficiency because similar changes may be produced by the administration of goitrogens.
TREATMENT OF POSTMENOPAUSAL OSTEOPOROSIS WITH OESTROGENS AND ANDROGENS
Authors: Hernberg C. A.
Published: December 2008

Fifteen patients with postmenopausal osteoporosis and 51 postmenopausal women without osteoporosis were subjected to intermittent treatment with oestrogens and androgens during 2 to 8 years.

In the patients with osteoporosis there was prior to treatment a considerable loss of height which ceased more or less during therapy.

In the nonosteoporotic postmenopausal women there was a negligible reduction in height during treatment in comparison to control cases of the same age group.
ÜBER DIE BEZIEHUNGEN ZWISCHEN DEM THYREOIDALEN UND PERIPHEREN JODSTOFFWECHSEL BEI SCHILDDRÜSENGESUNDEN UND HYPERTHYREOSEN
Authors: Klein Erich
Published: December 2008

In 28 euthyroid persons and 22 patients with hyperthyroidism several data of thyroidal and peripheral iodine metabolism were measured. A normal thyroxine/triiodothyronine-ratio of 100/0–85/15 has been found. With increasing age the turnover of iodine by the thyroid gland and the peripheral turnover of thyroxine proved to be accelerated, whereas the protein bound iodine in blood remained unchanged. Most hyperthyreotic patients showed an altered ratio of hormone secretion. The greater the amount of thyrogenic triiodothyronine in blood the slower was the thyroidal conversion of 131I to organically bound iodine (PB131I), and the smaller were the extrathyroidal organic iodine, the hormonal iodine in blood, the daily turnover of hormonal iodine and the oxygen consumption. The relations between the several data are explained by use of a 5 compartment modell of iodine metabolism.
TROPHIC HORMONE CONTENT OF THE ANTERIOR LOBE OF THE PITUITARY GLAND IN NORMAL AND CASTRATE MALE DOGS
Authors: Davidson Julian M. , Contopoulos Alexander N. , Ganong William F.
Published: December 2008

Pituitary FSH, ICSH, and TSH activities of intact and castrate male dogs were assayed in hypophysectomized immature female rats by determining the minimum amount of anterior pituitary tissue necessary to produce a response characteristic of each of these hormones. In intact dogs only, pituitary ACTH and GH content were also determined. The minimum effective doses obtained for intact dogs in fractions of anterior pituitary were: FSH – 1.5, ICSH – 0.25, TSH – 0.016, ACTH – 0.025, GH – 0.125. Castration had no significant effect on TSH content, but resulted in a sixteen-fold increase in FSH content and a two-fold increase in ICSH content of the pituitary gland.
SUBACUTE THYROIDITIS WITH ELEVATED SERUM ALKALINE PHOSPHATASE LEVEL
Authors: Vogt Jörgen Herman
Published: December 2008

A case of subacute thyroiditis is recorded, in which a transient rise in serum alkaline phosphatase values leads to the hypothesis of a transient parathyroid hyper-activity induced by the inflammation of the thyroid tissue in which the parathyroid may be embedded.