bluuebunny/crossref_metadata_2025 huggingface dataset:
Somatostatin, insulin and glucagon after arginine stimulation in active and treated acromegaly
Authors: Skare Ståle , Kriz Vera , Hanssen Kristian F.
Published: December 2008

Abstract. Ten acromegalic patients, 28–71 years old, were compared with 10 normal controls, 21–39 years old. In another study, 7 patients with active acromegaly, 19–70 years old, were investigated before and 4–9 months following transsphenoidal adenectomy and radiation. They were all investigated following an arginine infusion (0.5 g/kg/20 min).

Although the mean plasma somatostatin (somatotrophin release inhibiting factor (SRIF)) was somewhat higher in acromegalic patients compared to normal controls (mean basal values 21 ± 3.8 and 16.6 ± 2.1 pmol/l, respectively), the difference was not significant. The patients had higher serum insulin (peak values 118 ± 23.9 and 63 ± 11.8 mU/1, respectively) and lower plasma glucagon (peak values 171 ± 29.0 and 310 ± 52.7 pmol/l, respectively).

Plasma SRIF increased during arginine infusion, but the concentrations were similar before and following the operation (mean basal values 18.2 ± 2.6 and 15.2 ± 2.3 pmol/l, respectively). Serum insulin was significantly higher before the operation (peak values 154 ± 38.8 and 91 ± 24.9 mU/1, respectively). Plasma glucagon was similar before and after the operation (peak values 143 ± 23.4 and 127 ± 22.7 pmol/l, respectively).

Plasma SRIF is similar in active acromegaly and normal controls, and in acromegaly before and following treatment, despite differences in serum growth hormone (GH), serum insulin and plasma glucagon. This points towards a modulating role for GH on plasma SRIF, possibly by affecting the other islet cell hormones.
Responsiveness of pituitary hGH to GRH1-44 in juveniles with obesity
Authors: Pertzelan A. , Keret R. , Bauman B. , Josefsberg Z. , Ben-Zeev Z. , Szoke B. , Comaru-Schally A. M. , Schally A. V. , Laron Z.
Published: December 2008

Abstract. The response of plasma hGH to an iv bolus injection of GRH1-44 (1 μg/kg) was studied in 14 obese juveniles with a mean overweight of 4.7 ± 0.05 standard deviation score (sds). Two patterns of response were observed: in all 7 adolescents with 'simple' obesity not related to any particular disorder (group A) the response was good (a mean of 11.8 ± 2.4 ng/ml) whereas in 6 of the 7 juveniles suffering from syndromes associated with obesity (group B) the response was poor (a mean of 3.2 ± 1.4 ng/ml). This divergence in response could not be related to a difference in the degree of overweight. These results indicate that in group B with syndromes associated with obesity there may also be a pituitary impairment in addition to the hypothalamic defect.
An investigation into the effects of ketoconazole on testicular function in Wistar rats
Authors: Vawda A. I. , Davies A. G.
Published: December 2008

Abstract. Ketoconazole was administered orally to sexually mature Wistar rats and testicular function assessed. A single oral dose of 24 mg ketoconazole/kg body weight lowered plasma testosterone and DHT levels by 83 and 50%, respectively within 2 h, without altering gonadotrophin levels. Treatment for up to 7 days decreased epididvmal sperm number and motility and increased the proportion of abnormal sperm. The sperm appeared to be most affected 3 days after a single dose of ketoconazole and recovery had taken place by the seventh day. Daily treatment for up to 90 days also decreased sperm number and motility and increased the proportion of abnormal sperm, but did not affect testicular germ cells. No significant change was noted in the weights of the testis, epididymis, seminal vesicle and prostate; nor was there a change in testicular DNA, RNA and protein contents. Although fertility appeared to be impaired by long-term treatment, some of the treated rats mated successfully.
Effect of an acute injection of melatonin on the basal secretion of hypophyseal hormones in prepubertal and pubertal healthy subjects
Authors: Lisoni P. , Resentini M. , Mauri R. , De Medici C. , Morabito F. , Esposti D. , Di Bella L. , Esposti G. , Rossi D. , Parravicini L. , Legname G. , Fraschini F.
Published: December 2008

Abstract. It is well known that the pineal gland can modulate the secretion of pituitary hormones. Melatonin, the main hormone produced by the pineal gland, acts at the hypothalamic site, whereas hypophyseal sensitivity to melatonin seems to change with age. To investigate the influence of pubertal development on the role of the pineal gland in the regulation of the secretion of pituitary hormones, FSH, LH, Prl, TSH and GH responses to melatonin were evaluated in a group of 9 prepubertal and 10 pubertal healthy subjects of both sexes. Melatonin was given im at a dose of 0.2 mg/kg body weight at 3 p.m. Venous blood samples were drawn −20, 0, 20, 40, 60, 90, 120, 180 and 240 min, after melatonin injection. According to the same experimental protocol, venous blood samples were collected during a saline infusion on a separate occasion. FSH, LH, Prl, TSH and GH plasma levels were measured with RIA. In pubertal subjects, a significant rise in the mean Prl levels was seen 90 min after melatonin as compared with those during saline infusion. The Prl melatonin response area was significantly lower in prepubertal treated subjects and significantly higher in pubertal ones compared with the respective controls. The mean GH values showed a significant decrease 120 min after melatonin only in prepubertal subjects; no significant variations were seen in 8 of 10 pubertal subjects, whereas in the last 2 a marked increase was observed. Finally, under these conditions, melatonin did not influence the basal FSH LH and TSH levels.

These results seem to suggest that hypophyseal hormone reponses change with pubertal development.
Effects of pregnancy hormones on pancreatic islets in organ culture
Authors: Nielsen J. Høiriis , Nielsen Vibeke , Pedersen L. Mølsted , Deckert T.
Published: December 2008

Abstract. Pregnancy is associated with hyperinsulinaemia and decreased glucose tolerance which may lead to gestational diabetes. Sera from pregnant women in the last trimester were found to stimulate insulin secretion of mouse pancreatic islets maintained in organ culture suggesting a direct effect of pregnancy hormones and/or metabolites on the endocrine pancreas. Previous studies have shown that progesterone and human placental lactogen (hPL) had direct effects on isolated islets and in the present study the effects of combined addition of these hormones to the cultured islets were evaluated. hPL, 1 μg/ml was found to prevent the decrease in the islet insulin content due to progesterone 100 ng/ml, and hPL induced an increase in the DNA-content compared with the progesterone treated islets. The effect of the hormones on the DNA synthesis was evaluated by incorporation of [3H]thymidine into newborn rat islets. Progesterone in a high concentration, 1 μg/ml, inhibited while 0.1 and 1 μg/ml hPL stimulated the [3H]thymidine incorporation. These results indicate that progesterone may contribute to the increased glucose-induced insulin release during pregnancy and hPL to the β-cell hyperplasia. Since progesterone and hPL counteracted each other with regard to both insulin content and DNA-synthesis in the islets, the direct interaction between these two hormones on the β-cell may be of importance for the changes in glucose metabolism during pregnancy.
Early diagnosis of 11β-hydroxylase deficiency in two siblings confirmed by analysis of a novel steroid metabolite in newborn urine
Authors: Hughes I. A. , Arisaka O. , Perry L. A. , Honour J. W.
Published: December 2008

Abstract. Plasma and urinary steroid measurements are reported in 2 normotensive newborn female siblings with virilized external genitalia due to 11β-hydroxylase deficiency. Plasma 11-deoxycortisol concentrations were markedly elevated whereas 17OH-progesterone concentrations were not raised. Plasma renin activity was suppressed, but increased to levels characteristic of infancy within 4 weeks of treatment. The enzyme defect was confirmed by measurement of increased urinary excretion of tetrahydro-11-deoxycortisol. A more polar steroid metabolite, 6α-hydroxytetrahydro-11-deoxycortisol was also determined by gas chromatographic and mass spectrometric analysis. Analysis of metabolites in urine is an additional specific marker to plasma 11-deoxycortisol measurement for the diagnosis of 11β-hydroxylase deficiency in early infancy.
Effect of oestrogen or cyproterone acetate treatment on adrenocortical function in prostate carcinoma patients
Authors: Schürmeyer Th. , Graff J. , Senge Th. , Nieschlag E.
Published: December 2008

Abstract. The antiandrogen cyproterone acetate (CA), as well as oestrogens have been reported to influence pituitary-adrenal function in prostate cancer patients, but the clinical relevance of these findings is unknown. We therefore investigated serum cortisol (F), dehydroepiandrosterone sulphate (DS), testosterone (T) and prolactin (Prl) levels in patients treated with CA or oestradiol undecylate for at least 6 months. Hypothalamic-pituitary-adrenal function was further assessed by analysis of diurnal hormone variation and by ACTH stimulation and dexamethasone suppression tests. To differentiate between direct CA or oestrogen effects and secondary effects resulting from therapy-induced hypogonadism, we performed similar tests in untreated normogonadal and hypogonadal patients. CA treatment effected a significant decrease in serum F (−40%), DS (−73%) and T (−58%) levels and an increase in serum Prl (+118%). Oestrogen treatment resulted in markedly lowered T levels (−89%), slightly elevated serum F (+24%) and significantly increased serum Prl (+192%). Corresponding changes of F, DS and Prl could not be found in the untreated hypogonadal controls, thus indicating a direct drug-related effect. Neither diurnal rhythmicity of serum F nor adrenal response to ACTH stimulation or sensitivity to dexamethasone suppression significantly changed under CA or oestrogen treatment. We conclude that, although serum F levels may decrease under CA or increase slightly under oestrogen therapy for prostate carcinoma, these findings do not justify specific treatment, since neither clinical side effects nor an impairment of hypothalamic-pituitary-adrenal feedback occurs.
Priming procedure and cell isolation for study on luteal cell response to peptide hormone in the rat
Authors: Kumai A. , Asakai R. , Sakamoto S. , Sassa S. , Okamoto R.
Published: December 2008

Abstract. The objective of this study was to develop a method of isolating luteal cells from the ovaries of immature rats pretreated with pregnant mare serum gonadotrophin (PMSG). After the ovaries were digested by collagenase and trypsin, the corpora lutea were obtained from the tissues, gently pressed in a test tube, and then placed on a sucrose density gradient. The two bands that appeared in the tube after centrifugation were designated S1 (top band) and S2 (bottom band). Progesterone and 20α-dihydroprogesterone (20α-DHP) secreted by the isolated cells during short-term incubation were measured by radioimmunoassay (RIA). A larger amount of progesterone, i.e., 60 to 260 ng/105 cells, was secreted by S1 cells than by S2 cells during the 18-h incubation. These results suggest that this simple procedure for isolation of luteal cells may provide a suitable model for in vitro studies of the luteal function.
Thyroid function in hyperemesis gravidarum
Authors: Bober S. A. , McGill A. C. , Tunbridge W. M. G.
Published: December 2008

Abstract. Twenty-five patients with severe persistent vomiting were studied. On admission they were given the diagnosis of hyperemesis gravidarum. Hyperemesis was defined as vomiting of sufficient severity to warrant admission to hospital and iv therapy, which was not associated with any other condition known to cause vomiting other than the pregnancy itself. Ten (40%) of the patients had free thyroxine levels which were elevated on admission with hyperemesis. The free thyroxine normalised when the patients were well but still pregnant and remained normal post partum. Longitudinal data for nine other thyroid parameters are given and all illustrate the transient nature of the disturbed function in hyperemesis gravidarum.
Isolation, purification and culture of Sertoli cells from immature piglet testes
Authors: Renier G. , Gaulin J. , Gibb W. , Simard P. , Leung T. K. , Collu R. , Ducharme J. R.
Published: December 2008

Abstract. Several studies suggest a role of Sertoli cells in the control of Leydig cell steroidogenesis. In order to verify this hypothesis, we have developed a system for the purification of pig Sertoli cells. These cells were then characterized by their morphological appearance in light and electron microscopy, their ability to bind [125I]follicle stimulating hormone (FSH) and their functional capacity as evaluated by adenosine 3',5' monophosphate (cAMP) accumulation and lactate production when in primary culture under basal and FSH-stimulated conditions.

Crude Sertoli cell suspensions from immature porcine testes were fractionated on discontinuous Percoll gradients (densities 1.025, 1.039, 1.055, 1.080 g/ml). Highly purified Sertoli cells were contained in the second band (d: 1.039) generated on the gradient. These cells demonstrated morphological and functional integrity as evidenced by binding specifically [125I] FSH and by responding to FSH stimulation (by an increased production of cAMP and lactate after 3 days in primary culture), but not to human chorionic gonadotrophin (hCG).

This preparation represents a useful model for the study of Sertoli cell functions and their interation with Leydig cells in the regulation of testicular steroidogenesis.
Ovine corticotrophin-releasing factor in dogs: dose-response relationships and effects of dexamethasone
Authors: Kemppainen R.J. , Filer D. V. , Sartin J. L. , Reed R. B.
Published: December 2008

Abstract. Dose-response relationships between iv bolus injections (0, 0.1, 1 or 10 μg/kg) of synthetic ovine corticotropin-releasing factor (oCRF) and plasma immunoreactive (i) ACTH and cortisol concentrations were examined in healthy, conscious dogs. All doses of oCRF resulted in elevated plasma iACTH and cortisol levels over those of the controls. Maximum (or Peak) plasma iACTH concentrations were generally observed 20–30 min after oCRF and the magnitude of these peaks was a linear function (P<0.001) of the logarithm of the oCRF dose. The time of peak cortisol concentrations was more variable but the peak cortisol level was also linearly related (P< 0.001) to the logarithm of the oCRF dose. An estimate for the response areas for both hormones demonstrated a quadratic (P < 0.05) relationship with the logarithm of the oCRF dose. The relationship between oCRF and the iACTH response suggested a progressively greater response at increasing oCRF doses while a maximally effective oCRF dose was predicted in the cortisol response area relationship. Graded (0, 0.01, 0.1 or 1 mg/kg) bolus doses of dexamethasone produced a dose-dependent (P < 0.03) decline in baseline plasma iACTH levels and a non-dosedependent suppression in baseline plasma cortisol. Pre-treatment with 0.001 mg dexamethasone/kg 4 or 8 h before injection of 1 μg oCRF/kg did not alter the plasma iACTH or cortisol response; however, 0.1 mg dexarhethasone/kg administered at these times totally abolished the responses to oCRF. An intermediate dose (0.01 mg/kg) of dexamethasone inhibited the plasma iACTH response by an average of 79% (P<0.01) when administered 4 h before oCRF, but did not significantly alter this response when given 8 h prior to oCRF. The plasma cortisol response to oCRF was inhibited (P < 0.01) when 0.01 mg dexamethasone/kg was given as a 4 h, but not as a 8 h, pre-treatment. Iv administration of oCRF produces a profound, dose-dependent stimulation of the pituitary-adrenocortical axis of dogs and should prove useful in studies of this system.
Human foetal prolactin but not thyrotropin secretion is decreased by bromocriptine
Authors: Roti Elio , Robuschi Giuseppe , Alboni Alessandro , d'Amato Lorenzo , Montermini Mara , Gardini Eliana , Salvi Mario , Borciani Elisabetta , Dall'Aglio Elisabetta , Bisi Sandra , Zammarchi Giuseppe , Lasagni Remo , Gnudi Angelo , Braverman Lewis E.
Published: December 2008

Abstract. In the adult, dopamine inhibits prolactin (Prl) secretion and less so thyrotropin (TSH) release. Little information is available concerning the role of dopaminergic stimuli in the regulation of TSH and Prl secretion in the term human foetus. The dopamine agonist, bromocriptine (5 mg), or placebo were randomly administered orally to 120 pregnant women during labour. Maternal and foetal cord blood was obtained at parturition and analyzed for Prl, TSH, T4, T3 and rT3 concentrations. Since the time of parturition is unpredictable, maternal and cord blood hormone values were grouped at intervals of time from the time of bromocriptine or placebo administration to delivery. Hormone values were compared between the bromocriptine and placebo groups by two-way analysis of variance (ANOVA). Bromocriptine markedly inhibited maternal serum Prl conentrations compared to values in the placebo treated women (P < 0.001) and this decrease was more marked as the time interval between bromocriptine administration and delivery increased (P < 0.001, regression analysis). Cord blood Prl was also significantly lower in newborns whose mothers received bromocriptine (P < 0.001). Bromocriptine significantly inhibited maternal serum TSH concentrations as compared to values in women treated with placebo (P < 0.006). In contrast, bromocriptine administration did not affect cord blood TSH concentrations. These findings suggest that bromocriptine crosses the term human placenta and suppresses foetal Prl secretion. In contrast to the small inhibition of TSH secretion in pregnant women, bromocriptine does not affect foetal TSH secretion suggesting that regulation of TSH secretion in the term foetus may not be under dopaminergic control.
Characterization of the pituitary response in the TRH test by kinetic modeling
Authors: Swartz Conrad M. , Wahby Victor S. , Vacha Ruth
Published: December 2008

Abstract. Applying the principles of chemical kinetics to the time course of TSH concentrations after TRH infusion, individual values for total TSH release from the pituitary, TSH elimination and release rates, and latency for TSH release were found for 40 patients. Justification for using the observed peak TSH elevation as a consistent reflection of the total TSH release was provided by the high correlation between these two (r = 0.97, P < 0.001). Kinetic modeling indicated that the most consistent reflection of total pituitary TSH response is the TSH elevation over baseline 35 min after TRH (with the peak expected 30 min post-TRH), rather than the area under the curve.
The effect of oestriol and tamoxifen on oestradiol induced prolactin secretion in anaesthetised rats
Authors: Gilna Paul , Martin Finian
Published: December 2008

Abstract. In ovariectomized rats oestradiol and oestriol administered sc for 5 days increased basal plasma prolactin in a dose related manner to similar maximal values. The data fitted log dose-response curves. Oestradiol was about 12 times more potent than oestriol. These dose response relationships were retained on thyrotrophin releasing hormone (TRH) administration (50 ng iv, blood sampled 5 min post TRH). In addition, significantly higher maximal response values for both oestradiol and oestriol were now seen. The relative potency also increased in oestradiols favour.

We subsequently examined the effect of co-administering oestriol with oestradiol on plasma secretory responses to a single dose of oestradiol in young male rats: Oestriol (30 μg) potentiated increases in basal plasma prolactin, TRH stimulated prolactin secretion and radioimmunoassayable pituitary prolactin in rats in response to a single sc injection of oestradiol (10 μg). Tamoxifen, administered once also potentiated these responses to a single sc injection of oestradiol. However, if the tamoxifen was administered sequentially i.e. 48 and 24 h before or 48 and 24 h before and simultaneous with the oestradiol the potentiation was completely reversed.
The effect of maternal thyroidectomy prior to conception on foetal brain development in sheep
Authors: Potter B.J. , McIntosh G. H. , Mano M. T. , Baghurst P. A. , Chavadej J. , Hua C. H. , Cragg B. G. , Hetzel B. S.
Published: December 2008

Abstract. Merino ewes were surgically thyroidectomized, and mated 6 weeks later when their plasma thyroxine (T4) levels were negligible. Their foetuses were delivered by hysterotomy at 52, 71, 84, 98, 125, 140 days gestation or at term (150 days). Despite the very low levels of T4 in maternal plasma, the concentrations of T4 in foetal plasma were not significantly different after 71 days gestation from those of foetuses of sham-operated (control) ewes. Foetal brain and body weights, however, were reduced from 71 days compared to those of foetuses of sham-operated ewes. The foetal brain weights but not the body weights were restored to normal from 125 days to term. In additon to the weights, cell number (DNA) and cell size (protein:DNA ratio) appeared to be normal in the neonatal brain at parturition and this was confirmed by histological examination of the brains. Thus lack of maternal thyroid hormones in early pregnancy may cause a reduction in brain and body growth in the foetus which, in the case of the brain, appears to be restored to normal after the onset of foetal thyroid function.
Free fatty acids and pancreatic function in the duck
Authors: Gross R. , Mialhe P.
Published: December 2008

Abstract. The isolated perfused duck pancreas was used to study the effect of free fatty acids (FFA) on pancreatic function in vitro and to determine whether the FFA-glucagon negative feedback mechanism resulted from a direct inhibitory effect of FFA on the pancreatic A cell. Oleate, 2 mmol/l, increased the output rates of pancreatic somatostatin, glucagon and insulin. As there is poor morphological evidence in the duck for somatostatin to act as a paracrine intra-islet modulator, we reproduced in the pancreatico-duodenal artery, the rise in somatostatin level obtained in the pancreatic effluent after oleate. In these conditions the rises in glucagon and insulin secretions after oleate treatment were, respectively, reversed and suppressed, thereby reproducing observations previously made in vivo. Consequently, we may assume that the negative FFA-glucagon feedback mechanism that operates in vivo for physiological FFA variations does not result from a direct effect of FFA on the A cell, but may rather be mediated by an increase in pancreatic somatostatin secretion.
Effects of ACTH on RNA synthesis and migration in the adrenal cortex cells of the young rat, as shown by radioautography
Authors: Magalhães Maria C. , Vitor A. Bonito , Magalhães M. M.
Published: December 2008

Abstract. The effect of ACTH on the RNA synthesis in adrenal zona fasciculata cells of the young rat were studied by light and electron microscope radioautography. Two units of ACTH were administered sc to animals and immediately followed by an iv injection of [3H]uridine. ACTH-injected and control rats, which received the isotope alone, were sacrificed at various time intervals. Labelling over extranucleolar areas was higher in the ACTH-treated animals at 20 min, then becoming lower than in the controls at 60 min and 24 h. Nucleolar radioactivity, however, was consistently decreased by ACTH at all experimental times. Apart from these changes in the rate of synthesis, the over-all curves of labelling were similar to those in the control animals with a striking peak at 1 h. The short-term increase in extranucleolar RNA synthesis observed after ACTH injection was considered to be consistent with the hypothesis that an enhanced extranucleolar synthesis of mRNA takes place early in stimulated animals and is associated with the synthesis of steroidogenic proteins. On the other hand, the relatively decreased uridine uptake of the label by the nucleolus in ACTH-treated animals, suggests an inhibition of nucleolar transcription with diminished pre-rRNA formation in treated animals.
Effects of angiotensin II infusion on the early morning surge of ACTH and on o-CRH-provoked ACTH secretion in normal man
Authors: Haller H. , Hensen J. , Bähr V. , Oelkers W. , Exner P. , Windfuhr L.
Published: December 2008

Abstract. The question of whether elevated plasma angiotensin II (All) levels modulate ACTH secretion in man still awaits a definite answer. We performed two sets of experiments pertinent to that problem:

Seven healthy young males each received All (5 ng/kg/min) and sham infusions on different days in a randomized sequence from 03.00 h to 06.00 h in the morning, while plasma ACTH and cortisol were measured every 20 min. Mean blood pressure rose by about 10 mmHg during All infusion. Mean plasma ACTH levels were slightly higher with All than with sham infusion in every single individual (P <0.05). Differences in a pre- and post-infusion period were significant. Plasma cortisol levels were almost identical with or without All infusion.

Nine healthy young males received All (5 ng/kg/min) or sham infusions on different days from 16.30 h to 20.00 h in a randomized sequence and a 100 μg o-CRH injection at 17.00 h. Plasma ACTH and cortisol were measured every 15 or 30 min between 16.30 h and 20.00 h. Mean blood pressure rose by about 14 mmHg during All infusion. The rapid increment and further change in plasma ACTH and cortisol was not significantly different between the All and sham infusion studies. Conclusions: The dose of All infused was probably just above the threshold of ACTH stimulation, although All plasma levels obtained were probably far above the physiological range. On the adrenal level, a vasoconstrictor effect of All may have prevented stimulation of cortisol. This may be different in states of sodium depletion with reduced vascular effects of AII. The CRH experiment supports the idea that All enhances hypothalamic CRH release rather than directly stimulating ACTH on the pituitary level.
Effect of prostaglandin D2 on the release of luteinizing hormone and prolactin in castrated and intact male rats
Authors: Wogensen Lise , Warberg Jørgen
Published: December 2008

Abstract. One, 5 or 20 μg of prostaglandin D2 (PGD2) was infused into a lateral ventricle of the brain of anaesthetized intact or castrated male rats, and the response of luteinizing hormone (LH) and prolactin (Prl) was determined. PGD2 stimulated the release of LH in both groups of rats. The greatest LH-response was observed in the castrated rats, where the lowest dose of PGD2 (1 μg) caused the greatest LH response. This dose was ineffective in the non-castrated animals. PGD2 had no effect on the release of Prl neither in intact nor in orchidectomized rats. It is concluded that PGD2 is capable of stimulating the release of LH in male rats and that the stimulating effect is intensified by removal of the gonadal negative feedback effect on the hypothalamo-pituitary unit.
Effects of phorbol esters on protein phosphorylation and free T3 release by mouse thyroid lobes
Authors: Haraguchi Kazutaka , Endo Toyoshi , Onaya Toshimasa
Published: December 2008

Abstract. Phorbols stimulated 32P incorporation into several proteins in mouse thyroid lobes. Phosphoproteins (34 K and 23 K) were detected by SDS-polyacrylamide gel electrophoresis and autoradiography. Among phorbols tested, 12-O-tetradecanoyl-phorbol-13-acetate (TPA) was the strongest stimulator of protein phosphorylation. On the other hand, TPA at 50– 200 ng/ml significantly stimulated free T3 release by mouse thyroid lobes. The stimulatory effect of TPA was not additive to that of TPA or dibutyryl cAMP. TSH stimulation of free T3 release by mouse thyroid lobes, however, was significantly inhibited by H-7 (an inhibitor of protein kinase C) at a concentration of 50 μm. These results suggest that protein kinase C may play some role in thyroid hormone secretion by phosphorylating the endogenous substrates.
Cannulation of the utero-ovarian vein in intact ewes: hormone concentrations and blood gas levels during the oestrous cycle and early pregnancy
Authors: Hooper S. B. , Walker D. W. , Thorburn G. D.
Published: December 2008

Abstract. A technique for implanting and maintaining catheters in both utero-ovarian veins (UOV) of intact, conscious sheep has been developed. Both UOV catheters remained patent for more than 2 weeks in 72.7% of animals. In non-pregnant ewes, large pulses of PGF2α were observed in UOV plasma collected on days 13 to 16 of the cycle (frequency 1.3 ± 0.2/12 h; pulse height range 1.0–26.9 ng/ml). In contrast, on days 13 to 16 of gestation, significantly (P < 0.001) fewer pulses of PGF2α (frequency 0.42 ± 0.2/12 h) were observed in both UOVs of pregnant ewes, which were significantly (P < 0.001) smaller in amplitude (pulse height range 1.4–4.9 ng/ml). The maintenance of the corpus luteum (CL) during early pregnancy may therefore directly result from a decreased uterine PGF2α release.

During the luteal phase (day 4–12), the PO2 of UOV blood draining an ovary containing a CL (UOV/CL) was significantly higher than blood in the contralateral UOV (P <0.001). By days 15 and 16 of the cycle, the PO2 of UOV/CL blood had decreased and was not significantly different to that observed in the contralateral UOV (P >0.1). On day 17, the PO2 of blood in both UOVs was elevated significantly compared to levels observed on the two preceding and the two following days (P < 0.001). We consider that the higher PO2 in UOV/CL blood resulted from a very high luteal blood flow, and that the decrease on days 15 and 16 of the cycle resulted from a decline in luteal blood flow during luteolysis. The subsequent increase in PO2 of blood from both UOVs on day 17 was considered to result from an increased uterine blood flow.
Glucose tolerance in early pregnancy
Authors: Buch Inge , Hornnes Peter J. , Kühl Claus
Published: December 2008

Abstract. The effect of pregnancy on oral glucose tolerance (50 g of glucose) and plasma insulin and glucagon responses to oral glucose was studied in weeks 10 and 32 of pregnancy and again 1 year post partum in 12 normal women. Already in week 10, fasting plasma glucose was decreased and the glucose-induced insulin secretion increased as compared with post partum. However, glucose tolerance was not affected at this time. In week 32, glucose tolerance had deteriorated, although the levels of both fasting and glucose-induced insulin were higher than those found in early pregnancy and post partum. At all investigations fasting plasma glucagon and the suppression of plasma glucagon after oral glucose were similar, indicating that glucagon is not implicated in the changes in glucose homeostasis seen in pregnancy. It is concluded that glucose tolerance is unaltered by pregnancy in week 10. Pregnancy has, however, at this very early stage already affected glucose homeostasis as seen by the decrease in fasting plasma glucose and the increase in the insulin response to glucose.
Human decidua synthesizes placental protein 14 (PP 14) in vitro
Authors: Julkunen Mervi
Published: December 2008

Abstract. Human decidua was found to synthesize and secrete placental protein 14 (PP14). The presence of PP14 in tissue explants of decidua, foetal membranes and placenta from term pregnancy was demonstrated by radioimmunoassay. The PP14 content in decidua (1300 ±410 ng/100 mg tissue) was higher than in chorion (570 ± 120 ng/100 mg; P < 0.01), amnion (240 ± 100 ng/100 mg; P < 0.001) or placenta (300 ± 130 ng/100 mg; P< 0.001). Three to 36 times more PP14 was released into culture medium by decidual explants compared with the other tissues, and cycloheximide decreased this release by 39%. Placental tissues released hardly any PP14. Decidual synthesis of PP14 was demonstrated by incorporation of [35S]methionine into immunoprecipitable PP14 in tissue culture.
A-ring reduction enhances the antigonadotropic potency of norethisterone
Authors: Garza-Flores Josué , Vilchis Felipe , García Gustavo A. , Menjívar Martha , Pérez-Palacios Gregorio
Published: December 2008

Abstract. To assess whether structural modifications on the A-ring of norethisterone (NET) could modify its antigonadotropic potency, comparative studies using NET, 5α-dihydro NET (5α-NET) and its 3β,5α and 3α,5α tetrahydro derivatives in castrated adult rats were undertaken. The antigonadotropic effect of these compounds was evaluated by measuring the serum and pituitary immunoreactive concentrations of LH and FSH following their chronic sc administration to animals depleted of progesterone receptors. The results demonstrated that 3β,5α-NET and 5α-dihydro-NET exhibited a significantly greater gonadotropic inhibiting activity as compared with that of their parent compound. The simultaneous administration of tamoxifen with 3β,5α-NET resulted in a significant diminution of its antigonadotropic potency, particularly for LH. These data indicate that the potent antigonadotropic effect of 3β,5α-NET metabolite was mediated via oestrogen receptors. The LH inhibitory activity of 5α-dihydro-NET was not suppressed by the non-steroidal antioestrogen administration, thus suggesting that 5α-NET might exert its effect via androgen receptors. The overall data were interpreted as demonstrating that metabolic conversion products of NET exhibit potent antigonadotropic effect. The data are consistent with an A-ring enhancement of the antigonadotropic potency of this synthetic progestin and open an alternate approach to the development of fertility regulating agents.
Ontogenesis of androgen receptors in the mouse submandibular gland: correlation with the developmental profiles of circulating thyroid and testicular hormones
Authors: Minetti Conceicão A. S. A. , Valle Luiz B. S. , Fava-De-Moraes Flávio , Romaldini João H. , Oliveira-Filho Ricardo M.
Published: December 2008

Abstract. Specific binding of the synthetic androgen, [17α-methyl-3H]methyltrienolone, to the cytosol fraction of the submandibular salivary gland (SMG) of male mice was studied in relation to the developmental profiles of testosterone and thyroid hormones in blood. The peak rise of serum triiodothyronine (T3) at prepubertal age was closely related to both the increase of maximal androgen-binding capacity in SMG and the conspicuous surge of proliferative activity as indicated by increased rate of glandular DNA content. Also, 2-month thyroidectomized mice had an age-related, strong reduction in the number of androgen-binding sites. On the other hand, the development of the secretory functions of the gland could be better related to the rise of circulating testosterone by days 25–30 of age. The results suggest that thyroid hormones play a very important role in the early induction and further maintenance of androgen receptors in the murine SMG.
Time course of the effect of streptozotocin on serum concentration of glucose and triglycerides and on hepatic drug metabolism in the male rat
Authors: MacFarlane Marion , Skett Paul
Published: December 2008

Abstract. Streptozotocin (STZ) causes a rise in serum glucose, triglycerides and ketones and a fall in insulin and also leads to changes in drug metabolism. Results from rats left for 20 days indicate that there is no correlation between the effects of STZ on hepatic and serum parameters. The present study investigated the time course of the effect of STZ on hepatic drug metabolism, protein and cytochrome P-450 content and serum glucose and triglyceride concentration. STZ caused the induction of diabetes by 2 h which disappeared at 8 h and reappeared at 24 h. Drug metabolism was reduced after 1 h, returned to control levels at 2 h and remained there until 24 h. Liver protein was increased at 1 and 72 h but cytochrome P-450 was unaffected. The initial increase in serum parameters was not accompanied by changes in hepatic parameters and, thus, the two effects of streptozotocin may not be related.
Long-term results of stereotactic radiosurgery to the pituitary gland in Cushing's disease
Authors: Degerblad M. , Rähn T. , Bergstrand G. , Thorén M.
Published: December 2008

Abstract. Gamma radiation from 60Co delivered with stereotactic technique was given to the pituitary gland in 35 patients, aged 18–65 years, with Cushing's disease. The doses were 70– 100 Gy in each single irradiation. The size of the sella turcica was normal in the majority of the patients. The observation time was 3–9 years in 29 patients. Out of them, 14 (48%) obtained clinical remission and normal urinary cortisol after one irradiation. Eight achieved remission after two to four irradiations. In total, 22 out of 29 patients (76%) obtained remission. In 12 of them remission was obtained in 1 year and in another 10 within 3 years. No recurrences were observed. Improvement was seen in 2 patients after one and three irradiations. Bilateral adrenalectomy was performed in 5 patients owing to unsatisfactory effect of irradiation. Pituitary insufficiency with gonadotropin, thyrotropin or corticotropin failure was demonstrated in 12 of 22 patients in remission. This occurred 4 months to 7 years after the first irradiation. Another 6 patients were followed less than 3 years after the first irradiation. Two obtained remission after the first treatment, whereas the other 4 improved. Stereotactic pituitary irradiation is suggested as a non-invasive therapeutic alternative in Cushing's disease for example in patients with considerable surgical risk or as a supplement to pituitary microsurgery.
Thyrotropin – an episodically secreted hormone
Authors: Brabant G. , Ranft U. , Ocran K. , Hesch R. D. , von zur Mühlen A.
Published: December 2008

Abstract. A recently developed highly sensitive immunoradiometric thyrotropin (TSH) assay capable to distinguish between euthyroid and hyperthyroid TSH-levels was used to evaluate the secretion-pattern of TSH in 10 healthy male subjects by taking blood via an indwelling venous catheter at 10 min intervals over 24 h. Visual analysis revealed a pulsatile pattern of hormone release with an average of 10.3 peaks/24 h. Evaluation by computer assisted programs such as the Santen-program (8.9 peaks/24 h, amplitude 0.60 mU TSH/l), the 'Pulsar'-program (6 peaks/24 h, amplitude 0.61 mU TSH/l) or power-spectrum analysis (11.9 peaks/24 h) showed similar results. These data suggest a pulsatile mechanism of TSH secretion similar to other pituitary hormones.
The regulation of metabolic clearance rate of human FSH in mice by variation of the molecular structure of the hormone
Authors: Wide Leif
Published: December 2008

Abstract. The relationship between charge on human FSH (hFSH) molecules and their metabolic clearance rate (MCR) was investigated. The median charge of the hFSH molecules was expressed as their median mobility at electrophoresis in 0.075 m sodium veronal buffer, pH 8.6. MCR was estimated after single iv injection in mice of unfractionated and fractionated extracts of human pituitaries. There was a highly significant (P < 0.001) correlation between charge and MCR both for forms of FSH present within the individual pituitary and for FSH in different pituitaries. After the iv injection there was a gradual change to a more negative median charge of hFSH in plasma. This was explained by the more rapid clearance of the less negatively charged forms of hFSH and thus selective survival of different forms in the circulation. This is a most likely explanation for the differences in median charge between FSH in pituitaries and in sera of men and women of corresponding age. The results suggest that MCR of human FSH is controlled by a gonadal-pituitary feed-back mechanism which involves changes in the structure of the FSH produced by the pituitary. It is suggested that charge is one factor involved in the regulation of the survival of FSH in the circulation and that this is of physiological importance for the control of the ovarian function during the menstrual cycle.
Relationship between oral glucose tolerance and insulin sensitivity in healthy man and type 1 diabetic patients
Authors: Yki-Järvinen Hannele , Helve Eero , Koivisto Veikko A.
Published: December 2008

Abstract. The relationship between insulin sensitivity and oral glucose tolerance was studied in 8 conventionally treated type 1 diabetic patients (age 34 ± 4 years, relative body weight (RBW) 113 ± 5%) and in 11 healthy subjects (age 35 ± 3 years, RBW 114 ± 2%). In each subject and patient, oral glucose tolerance (75 g glucose) and in vivo sensitivity to insulin (euglycaemic clamp technique, 1 mU/kg/min insulin infusion) were measured. The response to oral glucose in the diabetic patients was measured during maintenance of similar peripheral plasma free insulin levels as in the normal subjects during the oral glucose tolerance test (OGTT). During the OGTT, the post-glucose plasma glucose values in the diabetic patients were markedly higher (P < 0.001) than in the normal subjects. During the clamp study, the rate of glucose metabolism in the diabetic patients (4.53 ± 0.58 mg/kg/min) was 37% lower than in the normal subjects (7.19 ± 0.67 mg/kg/min, P < 0.02). The area under the glucose curve was inversely related to the rate of glucose metabolism in both the diabetic (r = −0.72, P < 0.02) and the normal (r = −0.69, P < 0.02) subjects. The slope of the curve was substantially steeper in the diabetic than the control subjects. Thus, peripheral insulin sensitivity contributes to oral glucose tolerance both in healthy man, and even to a greater extent, in type 1 diabetic patients.
Long-term trophic action of α-melanocyte-stimulating hormone on the zona glomerulosa of the rat adrenal cortex
Authors: Robba Claudia , Rebuffat Piera , Mazzocchi Giuseppina , Nussdorfer Gastone G.
Published: December 2008

Abstract. The effects of α-melanocyte-stimulating hormone (α-MSH) on the rat adrenal cortex were investigated by coupled morphometric and radioimmunological techniques. Short-term α-MSH administration provoked a significant increase in the aldosterone plasma level along with a notable lipid droplet depletion in zona glomerulosa cells. Long-term α-MSH treatment induced a notable hypertrophy of zona glomerulosa cells and a further rise in the blood concentration of aldosterone. α-MSH did not affect zona fasciculata morphology and corticosterone plasma level. The possibility is discussed that α-MSH may be specifically involved in the control of the growth and steroidogenic capacity of rat adrenal zona glomerulosa.
Reduced urinary epidermal growth factor levels in Snell dwarf mutant mice
Authors: Lakshmanan J. , Perheentupa J.
Published: December 2008

Abstract. Because of findings implicating thyroid and growth hormones in the regulation of urinary EGF concentration, we determined urine and kidney EGF concentrations and relative kidney weights in both sexes of 8 week old dwarf mutant mice of the Snell strain and their normal littermates. Both male and female dwarfs had subnormal urine and kidney EGF concentrations. A female > male sex difference in both concentrations was present in the normal mice, but not in the dwarfs. The male > female sex difference in relative kidney weight, which has been demonstrated in normal mice of the Swiss-Webster strain, was not present in the normal or dwarf Snell mice.
Response of total and 'free' thyroid hormones and diiodotyrosine to bovine TSH in subclinical hypothyroidism
Authors: Benker G. , Rasche H. , Olbricht Th. , Meinhold H. , Teuber J. , Reinwein D.
Published: December 2008

Abstract. Thirty-three patients with Addison's disease were studied. Twenty-two had idiopathic Addison's disease; within this group, 14 patients had clinical or subclinical hypothyroidism, and 16 had increased titres of thyroid autoantibodies. Five patients had tuberculous, and eight had unclassifiable Addison's disease; only one patient in the latter group had evidence of thyroid autoimmunity. A stimulation test with 15 mU bTSH/kg was performed in three patients with Schmidt's syndrome (coexisting Addison's disease and manifest primary hypothyroidism), 15 patients with either subclinical hypothyroidism or increased titres of thyroid autoantibodies, 10 patients without thyroid involvement, and 10 normal controls. There was no detectable increase of 'free' and total thyroid hormones in Schmidt's syndrome. The mean increases after 3–4 h of T4, fT4, T3 and fT3 were 22, 35, 63 and 66%, respectively, in patients without thyroid involvement, and 13, 24, 46 and 45% in patients with subclinical hypothyroidism. 'Free' but not total thyroid hormones rose significantly (P <0.01) higher in patients without signs of thyroid involvement than in patients with subclinical hypothyroidism and/or thyroid autoantibodies. Thyroid hormone response to bTSH in Addison's disease with apparently healthy thyroid glands was not different from normal controls. Serum diiodotyrosine rose in all groups except in hypothyroidism; hypothyroid patients had, however, basal levels well within the normal range. Thus, thyroid hormone synthesis appears to be blocked at a point distal to diiodotyrosine formation in this particular situation. These results support the assumption that TSH elevation in idiopathic Addison's disease is due to coexisting thyroid autoimmunity and that it reflects incipient thyroid failure. This can be demonstrated by a diminished response of 'free' T4 and 'free' T3 to exogenous stimulation with bTSH.
Assay for thyroid growth stimulating immunoglobulins: stimulation of [3H]thymidine incorporation into isolated thyroid follicles by TSH, EGF, and immunoglobulins from goitrous patients in an iodine-deficient region
Authors: Schatz H. , Pschierer-Berg K. , Nickel J.-A. , Bär R. , Müller F. , Bretzel R. G. , Müller H. , Stracke H.
Published: December 2008

Abstract. Estimations were carried out of [3H]thymidine incorporation during culture of isolated porcine thyroid follicles in the presence of standard TSH or epidermal growth factor (EGF) both alone and together with anti-TSH or anti-EGF serum, and of immunoglobulins fractionated from the sera of patients from our endemic goitre area with iodine deficiency. A significant stimulation of thymidine incorporation was exerted by TSH when thyroglobulin was present in the culture medium, and also by EGF. TSH stimulation was abolished by anti-TSH serum, in contrast to the effect of EGF. Anti-EGF serum, on the other hand, blocked the effect of EGF, but not that of TSH. The sera of 20 out of 72 patients (27%) with euthyroid goitre (not operated on) and of ten out of 26 patients (38%) with recurrent euthyroid goitre contained immunoglobulins stimulating thyroid growth (TGI). There was no correlation of TGI with other thyroid antibodies. TGI have to be regarded as a pathogenetic factor of euthyroid goitre also in patients from an endemic region especially in recurrent cases.
Thyroxine monodeiodination in normal human kidney tissue in vitro
Authors: Boye Niels
Published: December 2008

Abstract. The present study deals with thyroxine monodeiodination in normal human kidney. To allow for comparison with previous reports, the present methods are similar to those used by others in rat tissue studies. The microsomal cell fraction of normal human kidney tissue was obtained by differential ultracentrifugation. The microsomes were incubated under various conditions and the deiodination products assayed with radioimmunoassay. A type I 5'-monodeiodinase was demonstrated, pH optimum around 6.5. Competitive inhibition was observed of T3 generation from T4 by rT3 with a Km of 3.0 μm and a Ki of 4 μm. Vmax was 26.1 pmol/min/mg protein. Likewise rT3 was generated from added T4, but it was rapidly degraded, while T3 was relatively stable as is the case in rat tissue preparations. Propylthiouracil inhibited 5'-deiodination in a dose dependent fashion with complete abolishment of deiodination at propylthiouracil concentration of 10−4m. Ipodate inhibited the reaction with complete inhibition at 10−2 m. The data demonstrate that a human kidney particulate cell-fraction contained considerable amounts of T4 deiodinases, very similar to the type I deiodinase of various rat tissue, although the handling of rT3 and the inhibitory action of this iodothyronine on T4 to T3 conversion seem to be slightly different in the two species.