bluuebunny/crossref_metadata_2025 huggingface dataset:
In vitro and in vivo TSH releasing activity of two new analogues of TRH
Authors: Roussel Jean-Paul , Tapia-Arancibia Lucia , Astier Hélène , Klingler Wolfgang
Published: December 2008

Abstract. The TSH releasing activity of two new analogues of TRH 'Pyr-(N3-Im-methyl)-His-Pro-NH-(n-amyl)' (I) and 'Pyr-His-Pro-(tyramine)' (II) was tested and compared with that of TRH in adult rats to test how structural modifications in the TRH molecule affect its biological activity: 1) in vitro in superfused pituitaries and 2) in vivo after ip injection, with measurement of TSH by RIA before and after addition of each secretagogue.

Analogue I was found to be more potent than both TRH itself and Analogue II in stimulating TSH release: at 10 nmol/l in vitro, the ratio of induced to spontaneous release was 4.13 ± 0.35, 2.98 ± 0.20, and 1.19 ± 0.17, respectively for each secretagogue, with a 50% effective dose of 6 × 10−9 mol/l for Analogue I and 5 × 10−8 mol/l for TRH. A similar order of potency in increasing plasma TSH (Analogue I > TRH > Analogue II) was found in vivo, as shown by dose-response curves. After a 4-day pre-treatment with TRH (2 × 100 μg/day) a similar TSH response to TRH and Analogue I (500 nmol/kg body weight) was observed. By contrast, the dose of Analogue II needed to obtain the same stimulatory effect on TSH release was twice as high.

The biological activity of TRH appears to be more effectively increased by replacing an H atom by an amyl group in the C-terminal amide function of the proline residue of TRH than by a tyramyl group in the same residue.
Thyroid hormone reserve in asymptomatic autoimmune thyroiditis
Authors: Deboel S. , Bonnyns M. , Jonckheer M. , Buydens P. , Smitz J. , Finne E. , Vanhaelst L.
Published: December 2008

Abstract. Basal (B) and peak (P) serum levels of thyroxine (T4), free thyroxine (FT4), triiodothyronine (T3), free triiodothyronine (FT3), and TSH were measured before and after oral TRH (40 mg) administration in 79 subjects affected with asymptomatic autoimmune thyroiditis (AAT) and in 69 normal subjects. The area under the curve (AUC) and peak values of T4, FT4, T3 and FT3 were considered as parameters of thyroid hormone reserve. Intrathyroidal iodine (ITI) was measured by the X-ray fluorescence method. The AAT subjects were divided into three groups on the basis of their basal and peak TSH values. In group I, these parameters were similar to those in the normal controls; in group II, basal TSH remained normal but peak TSH was significantly increased, and in group III both values were significantly increased. Group I differed from the controls by a decrease in P FT4 and AUC FT4, whereas in groups II and III B FT4 was also significantly lowered. T3 levels were similar in all groups except in group III, in whom they dropped. ITI was already lower in group I than in the controls. Its decline went further in groups II and III. An inverse correlation with significant r values was evidenced between log B and P TSH on one hand and log B FT4, P FT4 and AUC FT4 on the other. When group III was excluded, log P TSH was positively correlated with log B T3, P T3, AUC T3, and AUC F T3. The present study shows that the thyroid T4 reserve gradually decreases with the severity of AAT, and suggests that except in the most severe stage, a preferential T3 secretion occurs probably as a consequence of the decrease in intrathyroidal iodine.
Effect of 1,25-dihydroxyvitamin D3 on TSH secretion from rat pituitary cells in culture
Authors: Törnquist Kid , Lamberg-Allardt Christel
Published: December 2008

Abstract. The effect of 1,25-dihydroxyvitamin D3 ( 1,25(OH)2D3) on TSH secretion from rat pituitary cells was studied. When incubating cells with 1,25(OH)2D3 even at 100 × the physiological concentrations (10−8), no effect on basal TSH secretion was observed. The TRH-induced TSH secretion increased after a 24-h incubation with 10−8 mol/l 1,25(OH)2D3 (2.9 ± 0.2 ng/well vs 4.3 ± 0.5 ng/well, mean ± sd; P < 0.05). When serum was omitted from the incubation medium, the potentiating effect of 1,25(OH)2D3 on the TRH-induced TSH release was blunted. No effect on cellular protein content was observed after incubating the cells with 10−8 mol/l 1,25(OH)2D3. The results indicate that at unphysiological concentrations, 1,25(OH)2D3 affects the TRH-induced TSH secretion from pituitary cells. The physiological significance remains unclear.
Opioid peptides in the regulation of TSH and prolactin secretion in the rat
Authors: Rauhala Pekka , Tuominen Raimo K. , Männistö Pekka T.
Published: December 2008

Abstract. The effect of β-endorphin, met-enkephalin and leu-enkephalin on cold-stimulated TSH and prolactin secretion after infusion of the drugs into the 3rd ventricle or into the posterior hypothalamus (PH) was investigated in male rats. β-endorphin (0.25 μg/rat, but not 0.05, 0.5 and 1 μg/rat) increased and met-enkephalin (20 and 100 μg/rat) decreased TSH secretion when infused into the 3rd ventricle. After bilateral infusion into the PH, β-endorphin (0.25 μg/side, but not 0.05 and 1 μg/side) increased TSH secretion, but met-enkephalin (1 and 10 μg/side) induced no changes. β-endorphin (0.05–1 μg/rat) and met-enkephalin (100 μg/rat) both increased prolactin secretion when infused into the 3rd ventricle, but only a high dose of β-endorphin (1 μg/side) was effective after infusion into the PH. Leu-enkephalin had no effect on TSH or prolactin secretion at the hypothalamic level. These results favour the hypothesis that μ-receptors mediate the inhibitory effect and other types (possible ε-receptors) of opiate receptors mediate the stimulatory effect of opioid peptides on TSH secretion at periventricular sites. However, only stimulatory μ-receptors affect prolactin secretion at these sites. After infusion into the PH, the effect of a high dose of β-endorphin on prolactin secretion may also be mediated through periventricular sites, but its effect on TSH secretion is evidently mediated through opiate receptors in the PH.
Evidence that exteroceptive stimuli other than suckling have no major effect on plasma prolactin in lactating rats
Authors: Mattheij John A. M. , Swarts Hans J. M.
Published: December 2008

Abstract. The ability of exteroceptive stimuli from pups to increase plasma prolactin in lactating dams was investigated. Prolactin profiles were measured during 30 min of suckling followed by complete or partial separation from pups. Prolactin profiles were also measured subsequent to complete or partial isolation from pups in dams which had been with pups permanently before the experiment. In addition, plasma prolactin was measured in dams which after a night of isolation were partially united with pups. Finally, the effect of ether stress on prolactin profiles after interruption of suckling by pups was determined. Vigorous suckling after a period of isolation induced a sharp increase of plasma prolactin. Subsequent to pup removal, either partial or complete, prolactin profiles showed a widespread variation. Also dams which before experimentation were kept permanently with pups, showed a great variation in prolactin profiles subsequent to either complete or partial separation from pups. Plasma prolactin either decreased rapidly or gradually. In several dams a rapid or a gradual decline of plasma prolactin was interrupted by one or more episodes of prolactin release. Partial reunion with pups after a night of isolation, either in mid-lactation or in late lactation, did not induce a rise of plasma prolactin. It is concluded that exteroceptive stimuli from pups are not effective as prolactin releasing signal. Because ether stress did not induce a steep rise of plasma prolactin, we conclude that the episodic rises of plasma prolactin in dams, subsequent to partial or complete removal of pups, are due to spontaneous activity of the hypothalamo-pituitary system.
Diurnal plasma profiles of metabolite and hormone concentration in insulin-dependent diabetic patients during conventional insulin treatment and continuous subcutaneous insulin infusion
Authors: Hermansen K. , Møller A. , Christensen C. K. , Christiansen J. S. , Schmitz O. , Ørskov H. , Alberti K. G. M. M. , Mogensen C. E.
Published: December 2008

Abstract. In addition to hyperglycaemia, derangement of metabolic and hormonal control may play an important role in the development of microvascular complications in diabetes. Little, however, is known about the impact of insulin pump treatment on metabolic and hormonal parameters. In a 6-month prospective randomized study in insulin-dependent diabetics we therefore investigated the effects of continuous subcutaneous insulin infusion by pump (10 patients) and conventional insulin treatment (10 patients) on the 24-h profiles of blood glucose, glycerol, lactate, 3-hydroxybutyrate, insulin, glucagon and growth hormone by measuring the respective concentrations every 2 h.

We found that average blood glucose levels and HbA1c were significantly lower in the group treated by continuous subcutaneous insulin infusion as compared with the group on conventional insulin treatment. Furthermore, we observed an improvement in diurnal levels of lactate and 3-hydroxybutyrate in the pumptreated group which was not seen in the conventionally treated group. A slight increment in alanine was seen in the group treated with insulin pump. Serum growth hormone, glycerol, plasma free insulin as well as the daily insulin supply were unchanged and identical in the two groups. It is noteworthy that in the pump group, the decrease in blood glucose and 3-hydroxybutyrate takes place concomitantly with a significant suppression of glucagon.
Relationship between serum thyroxine concentration and dialyzable triiodothyronine fraction in patients with hyper-and hypothyroidism
Authors: Konno N. , Hagiwara K. , Taguchi H. , Nakajima A.
Published: December 2008

Abstract. The interrelationship between the dialyzable triiodothyronine (T3) fraction (DFT3), T3, and thyroxine (T4) was examined in various groups of patients with hyper- and hypothyroidism. Partial correlational analysis showed that DFT3 correlated significantly with T4 (r = 0.383, N = 114, P <0.001), but not with T3 (r = 0.132). DFT3 exceeded the normal range when T4 was supranormal. The relation between T3 and free T3 (FT3) was quadratic (R2 = 0.944, N = 112, P < 0.001). When the patients were divided into two groups according to T4 levels, the regression line between T3 and FT3 in patients with supranormal T4 was more than twice as steep as that obtained in patients with normal or subnormal T4 levels. In addition, the DFT3 and FT3 values were higher in patients with hyperthyroidism and both elevated T4 and T3 than in patients with hyperthyroidism and only elevated T3. The results indicate that T4 is a major factor influencing the DFT3 value, except when the T4-binding globulin concentrations vary markedly, and that the T4 level should be taken into account for a clinical evaluation of the FT3 concentration in hyper- and hypothyroidism.
The effect of minisomatostatin on anomalous growth hormone responses in acromegaly
Authors: Pieters G. F. F. M. , Smals A. E. M. , Smals A. G. H. , Gennep J. A. v. , Kloppenborg P. W. C.
Published: December 2008

Abstract. Twelve patients with active acromegaly were treated with the long-acting somatostatin analogue SMS 201-995 at a dose of 50 μg sc twice daily in the first 2 weeks of treatment and 100 μg twice daily thereafter. Four hours after the first injection of SMS, GH levels became normal in 8 of the 12 patients. The GH response after hpGRF administration was strongly suppressed by SMS. Paradoxical GH responses to TRH disappeared in 6 out of 7 patients during SMS. Paradoxical GH responses to LHR, however, persisted in 4 out of 4 patients. Paradoxical responses of GH after glucose loading disappeared in 2 out of 2 patients. We conclude that SMS normalizes most anomalous growth hormone kinetics in acromegaly. This drug offers a new tool in the treatment of this disease.
Hemiovariectomy and follicular growth in the immature rat
Authors: de Reviers M. M.
Published: December 2008

Abstract. Female rats were hemiovariectomized on day 1 (T2) or day 10 (T3) after birth. The population of growing follicles in the remaining ovary and the plasma levels of FSH an LH were compared to controls (T1) on post-natal days 20, 30 and 38. There was a non significant trend towards higher FSH and LH levels in hemicastrates. Hemicastration had a significant (P < 0.05) overall effect on the number of small (1 to 2 layers of granulosa cells) and preantral follicles (more than 2 layers of granulosa cells and diffuse antrum): small follicles were more numerous (P < 0.05) in ovaries of the T3 group, whereas preantral follicles were more numerous in the T2 group. Atresia was somewhat lower in hemicastrates compared to controls. The observed increase in the whole population of follicles, in the remaining ovary, may be attributed to several factors including a decrease in steroids and inhibin, an increase in FSH and/or a neural discharge signal. The increased number of follicles may constitute a reserve to maintain the characteristic ovulation pattern of the species in later life.
Heterogeneity of human luteinizing hormone. Detection and identification of α- and β-subunits in international reference preparations
Authors: van Ginkel L. A. , Loeber J. G.
Published: December 2008

Abstract. The charge heterogeneity of three international reference preparations containing biologically active human luteinizing hormone (LH) or its free α-or β-subunits, respectively, was investigated with isoelectric focussing in sucrose density gradients. The immunoreactive profiles throughout the pH-gradient were assessed with radioimmunoassay (RIA) systems specific for intact, i.e. undissociated, LH or free α- or β-subunits. For the preparation of intact LH (MRC 68/40), two peaks were found at pH = 7.69 and 8.05; for the α-subunit preparation (NIBSC 78/554), the peak values were 4.76, 5.04, 5.94, 6.70, 6.96, 7.35, 8.02, 8.72 and 9.32; and for the β-subunit preparation (NIBSC 78/556), the values were 7.60, 8.40, 8.55 and 9.61. These results are in excellent agreement with those obtained for a highly purified LH preparation (NM 14) which was prepared by one of us and on which we have reported earlier. In addition, with the abovementioned techniques, the spontaneous dissociation of MRC 68/40 into subunits upon incubation at 37°C in phosphate buffer was clearly demonstrated by the increased immunoreactivity in the profiles assessed with both RIA-subunit systems. It is concluded that charge heterogeneity of LHi, α- and β-subunits, as observed for different preparations, is confined to a limited population of forms. Differences between preparations are only quantitative. A single preparation, therefore, can be used as a general model for the study of human luteinizing hormone.
The effects of cyproterone acetate on statural growth in children with precocious puberty
Authors: Sorgo W. , Kiraly E. , Homoki J. , Heinze E. , Teller W. M. , Bierich J. R. , Moeller H. , Ranke M. B. , Butenandt O. , Knorr D.
Published: December 2008

Abstract. Forty-four patients (42 f, 2 m) with precocious puberty (31 idiopathic, 1 familial, 7 cerebral, 5 McCune-Albright) were treated with cyproterone acetate for periods of 1–8.75 years in different (P < 0.05) daily dosages of 117 ± 6.1 mg/m2 per day (x̄ ± sem, group A, N = 20) and 60.8 ± 2.42 mg/m2 per day (group B, N = 24). Thirty-three girls had experienced menarche before therapy at a mean age of 4.89 ± 0.42 years. Treatment was started at a chronologic age of 5.45 ± 0.33 years in the girls and 5.74 ± 1.34 years in the boys. At the time of evaluation, 31 of our patients had reached final height. With respect to the effects of treatment on statural growth, the Standard Deviation Scores were retrospectively determined for height, weight, and growth velocity. The initial Bayley-Pinneau height predictions were compared with final height and target height, and the skeletal maturation was studied. There were no significant differences between those parameters in the patients of group A and B or between treated and untreated subjects as far as final height and target height were concerned. It is concluded that cyproterone acetate administered orally at daily doses from 50–150 mg/m2 does not improve statural growth of patients with precocious puberty.
Effects of atrial natriuretic peptide, dopamine, and ouabain on aldosterone synthesis
Authors: Nakajima Sadao , Suzuki Hiromichi , Saito Ikuo , Saruta Takao
Published: December 2008

Abstract. This study was undertaken to examine the effects of atrial natriuretic peptide (ANP), dopamine, and ouabain, which each are considered to be a kind of natriuretic factor, on aldosterone synthesis in vivo and in vitro. In the in vivo experiments, during infusion of one of the natriuretic factors, ANP (64 pmol · min−1 · kg−1), dopamine (20 nmol · min−1 · kg−1) or ouabain (684 pmol · min−1 · kg−1), the stimulatory action of angiotensin II (20 pmol · min−1 · kg−1) or adrenocorticotropin (ACTH, 7 pmol · min−1 · kg−1) on aldosterone synthesis was investigated in 36 anaesthetized (pentobarbital, 40 mg/kg, iv) female rabbits. In the basal condition, aldosterone synthesis was suppressed slightly by each of the natriuretic factors. The stimulatory actions of angiotensin II and ACTH on aldosterone synthesis were significantly attenuated by pre-treatment with ANP and dopamine. However, ouabain infusion did not induce any changes in the synthesis of aldosterone, 18-hydroxycorticosterone (18-OHB), and corticosterone (B) in either the basal or the stimulated conditions. For the in vitro experiments, rabbit adrenal glomerulosa cells (105 cells/tube) were used. The effects of ANP and dopamine on the aldosterone synthesis revealed results identical to those from the in vivo study. However, in contrast to the in vivo study, ouabain completely inhibited the synthesis of aldosterone, 18-OHB and B. The above results obtained in vivo and in vitro suggest that ANP inhibits corticosterone methyloxidase II activity and dopamine inhibits corticosterone methyloxidase I activity. However, from the present study we were unable to specify the action of ouabain on the synthesis of aldosterone and its related substances.
Effects of metabolic inhibitors on hormone release, cyclic AMP levels, and oxygen consumption in rat pituitary cells in culture
Authors: Sletholt Kjersti , Magnusson Claes , Haug Egil , Gautvik Kaare M.
Published: December 2008

Abstract. The metabolic inhibitors antimycin A (2 μmol/l), dinitrophenol (0.5 mmol/l), and iodoacetate (6 mmol/l) were tested for their effects on hormone release, cAMP levels, and oxygen consumption in clonal strains of rat pituitary cells (GH3 cells). Basal release of growth hormone (GH) and prolactin (PRL) was reduced by all three inhibitors, and thyrotropin-releasing hormone (TRH) (l μmol/l) and K+ (50 mmol/l) stimulated hormone release were blocked. Trifluoperazine, a calmodulin antagonist, inhibited basal GH and PRL release at concentrations up to 30 μmol/l and stimulated above 50 μmol/l. The stimulatory effect of 80 μmol/l trifluoperazine on basal hormone release was eliminated by antimycin A, dinitrophenol, and iodoacetate, whereas the inhibitory effect of antimycin A, dinitrophenol and iodoacetate on basal hormone was not affected by 30 μmol/l trifluoperazine. None of the inhibitors had any effect on the level of cellular cAMP (i.e. intracellular plus extracellular). Oxygen consumption of GH3 cells was blocked by antimycin A, reduced by 25% by iodoacetate and increased by about 100% by dinitrophenol. In contrast, hormone secretion stimulated by TRH and K+ was not accompanied by any measurable alteration in oxygen consumption. Trifluoperazine (⩾ 80 μmol/l) reduced the basal oxygen consumption and blocked the stimulatory effect of dinitrophenol on oxygen consumption. In conclusion, inhibition of the energy generation of GH and PRL-producing cells severely affects the action of secretagogues, although stimulated hormone secretion may not be accompanied by any measurable increase in oygen consumption. The cellular energy supporting hormone secretion is mostly generated via oxidative phosphorylation.
Regulation of LH receptors and steroidogenesis in the foetal rat testis in vivo
Authors: Warren Dwight W. , Huhtaniemi Ilpo T. , Dufau Maria L. , Catt Kevin J.
Published: December 2008

Abstract. Foetal rats were injected with high doses of hCG or ovine LH (oLH) to determine if LH receptors were down-regulated and steroidogenesis impaired as is seen in the adult animal. Foetuses injected in utero with 52 μg/kg hCG had a prompt increase in intratesticular testosterone, demonstrating that the injected substance reached the foetal testis. Pregnant mothers were laparotomized and each foetus in one uterine horn injected with 52 μg/kg hCG. Twenty-four hours later, the foetal testes from both uterine horns were collected and free LH receptor content measured. In foetuses injected with hCG, free LH receptors were significantly reduced. LH receptors in foetal testes from the contralateral horn were not significantly different from those in controls. Foetuses injected with 52 μg/kg hCG at 17.5 days of gestation showed a delayed response in LH receptor up-regulation when compared with neonatal rats injected with comparable doses of hCG. Injection of foetal and neonatal rats with 400 μg/kg oLH showed no evidence of down-regulation, as is seen in the adult. Testes from foetuses injected with 52 μg/kg hCG 3 days earlier showed an increase in both basal and hCG-stimulated testosterone production during 3 h of incubation when compared with controls. These results show that the rat foetal testis in vivo does not demonstrate down-regulation of LH receptors or steroidogenic lesions of the testosterone synthetic pathway when exposed to high levels of hCG as does the adult rat testis. These results from the foetal testis in vivo are in agreement with results obtained from the foetal testis in vitro and the neonatal testis in vivo.
Immunoreactive somatomedin B in the human foetus and in women during pregnancy
Authors: Tham A. , Wetterberg L. , Sara V. R.
Published: December 2008

Abstract. Immunoreactive somatomedin B (RIA-B) was identified in foetal organ extracts, amniotic fluid and foetal serum in the second trimester. After separation using a G-200 neutral Sephadex column, the RIA-B activity in the cytosol prepared from foetal organs eluted after the void volume, suggesting the dominance of activity with the molecular weight of approximately 200 K. In contrast, the majority of the RIA-B activity in amniotic fluid eluted around the elution volume, suggesting dominance of activity with a molecular weight of approximately 5 K. Cord blood RIA-B levels were examined and found to be significantly lower than adult levels. A significant correlation between cord blood RIA-B levels, and neonatal weight was found. A longitudinal study during pregnancy showed that RIA-B is increased in both healthy women and in women suffering from hypopituitarism suggesting a pituitary-independent production of RIA-B during pregnancy.
Changes in catecholamine contents in ovarian follicular theca, progesterone contents in granulosa, and LH concentrations in peripheral plasma during the ovulatory cycle in the hen
Authors: Chotesangasa Ratana , Kamiyoshi Michiharu , Tanaka Katuhide , Tomogane Hiroshi , Yokoyama Akira
Published: December 2008

Abstract. By the use of high-performance liquid chromatography, the content of norepinephrine (NE) and epinephrine (E) in the theca of the largest and the second largest preovulatory follicle of the ovary of the hen was found to increase from 15 h (NE) or 18 h (E) to reach a peak 9 h (NE) or 9–6 h (E) before ovulation of the largest follicle. The content of progesterone in the granulosa of these follicles and the concentration of LH in the peripheral plasma of the same hen, both of which were measured by radioimmunoassays, showed a peak 6 h before ovulation. The results suggest that the catecholamines are involved in some events occurring in both follicles some several hours before ovulation of the largest follicle during the ovulatory cycle.
T3 stimulation of 2-deoxy-D-glucose uptake in cultured chick embryo carcass derived cells, requires neosynthesis of proteins
Authors: Gordon Amirav , Schwartz Henia , Gross Jack
Published: December 2008

Abstract. T3 stimulated, in a dose dependent manner, the uptake of 2-deoxy-D-glucose (2-DOG) into cultured chick embryo carcass derived cells. A significant increase in sugar uptake was seen already at a T3 concentration of 1 pmol/l. The stimulation of 2-DOG uptake increased with time during the 6 h of exposure to T3. The hormone also stimulated, within 45 min, the incorporation of [3H]leucine and [3H]uridine into the trichloroacetic acid precipitable material of these cells. Actinomycin-D (100 μg/l) and cycloheximide (1 mg/l) each were capable of blocking the stimulatory effect of 10−8 mol/l T3 on sugar uptake and on uridine and leucine incorporation. Thus, T3 in these cultured chick embryo cells stimulated sugar transport through processes dependent on neosynthesis of proteins. In this respect the effect of T3 is different from that seen in cultured chick embryo cardiomyocytes.
Age-dependence of the rat Leydig cell and Sertoli cell function.
Authors: Kühn-Velten Nikolaus , Bos Dagmar , Schermer Roland , Staib Wolfgang
Published: December 2008

Abstract. The first part of this study compares peripheral testosterone levels with intratesticular levels of the cytochromes P-450 of two key enzymes of androgen biosynthesis, i.e. mitochondrial cholesterol monooxygenase (P-450(cscc)) and microsomal steroid-17α-monooxygenase (P-450(C17α)) during puberty and early adulthood of male Wistar rats. From 4 to 10 weeks of age, the testosterone level increases 8.7-fold, the P-450(C17α) level 8.3-fold, but the P-450(cscc) level 24.5-fold as an indication of specific induction of this protein. From 13 to 50 weeks of age, the testosterone level remains constant, the P-450(cscc) level increases continuously by a factor of 1.4, but 62% of the P-450(C17α) content are lost. This discrepancy is explained by a divergent regulation of the cytochromes P-450 of the two steroid monooxygenases: a persisting induction of P-450(cscc) and a concurrent down-regulation of P-450(C17α) that may be a consequence of the high rate of Leydig cell steroid hydroxylation after puberty. Overlapping of both processes may (probably besides other developmental factors) result in a constant testosterone concentration in blood. The second part of the study compares testicular and epididymal levels of androgen-binding protein (ABP) with the peripheral testosterone level. The peripubertal increase in testicular ABP content is shown to be related only to the increase in testicular mass, whereas a specific accumulation of ABP occurs in the epididymis from 4 to 13 weeks of age. This pattern indicates an increasing secretory activity of the Sertoli cells that remains high during adulthood up to the 50th week. The parallelity of epididymal ABP accumulation and testosterone level confirms the concept of androgen-dependence of Sertoli cell secretory function.
Is thyrotropin-releasing hormone receptor involved in thyrotrope adaptation to starvation?
Authors: Hugues Jean-Noel , Wolf Bryan , Sebaoun Jacques , Buisson Nicole , Gourdji Danièle
Published: December 2008

Abstract. The aim of the present study was to delineate the involvement of TRH receptors in the thyrotrope adaptation to starvation (i.e. plasma TSH and thyroid hormone decrease, increased sensitivity to T3) by measuring [3H]TRH binding in euthyroid, hypothyroid and T3-substituted rats (175 ng/100 g body weight). Our results show that in euthyroid rats, starvation does not significantly modify either the affinity or the number of pituitary binding sites. In hypothyroid and T3-substituted rats, starvation does not alter the negative control exerted by T3 on the number of TRH binding sites. Our data indicate that the adaptation of thyrotrope to starvation does not primarily result from alterations of TRH binding sites.
Induction of transient hyperprolactinaemia in neonatal rats by direct or maternal treatment with the dopamine receptor blocker, sulpiride
Authors: Lewis Mark , Howie Peter W.
Published: December 2008

Abstract. Prolactin was measured in the plasma of neonatal rats after iv and ip injection of the dopamine receptor blocking drug sulpiride, and after its ip injection to neonatal rats' nursing mothers. The sulpiride dose PRL response relationship in 10 –25 day old neonatal rats was similar to that found in lactating rats, with a threshold sensitivity around 29 nmol sulpiride/kg body weight and a maximal response at about 2.9 μmol/kg. Absolute levels of PRL in the neonate (both peak and increment-over-basal) were, however, 90% lower than in adults. Treatment of lactating mothers with a maximally stimulatory dose of sulpiride (2.9 μmol/kg) twice daily for 4 days resulted in small but highly significant increases in neonatal PRL on days 1 and 2 but complete loss of response by day 4. These data demonstrate that there is a close similarity between the responses of maternal and neonatal rats to sulpiride and that transfer of the drug to the neonate via milk can induce neonatal hyperprolactinaemia. The subsequent loss of the neonatal PRL response on chronic exposure to sulpiride may indicate a degree of disturbance of hypothalamic dopaminergic mechanisms. In the clinical situation this would suggest that doses of dopamine receptor-blocking drugs used to enhance maternal milk production should be carefully chosen.
Androgens and oestrogens before and following oral testosterone administration in male patients with and without alcoholic cirrhosis
Authors: Gluud Christian , Dejgaard Anders , Bennett Paul , Svenstrup Birgit
Published: December 2008

Abstract. Compared with controls (N = 9), alcoholic cirrhotic men (N = 14) showed: significantly (P < 0.05) higher serum concentrations of sexual hormone binding globulin (SHBG), androstenedione, oestrone, oestradiol, non-protein bound oestradiol, and non-SHBG bound oestradiol; significantly (P < 0.05) lower concentrations of albumin and non-SHBG bound testosterone; no significant differences regarding concentrations of testosterone, dihydrotestosterone, non-protein bound testosterone, oestrone sulphate, and SHBG bound oestradiol. Following oral administration of 400 mg of micronized testosterone, serum concentrations of testosterone, dihydrotestosterone, androstenedione, and oestrone increased significantly (P < 0.05) in both groups, cirrhotic patients reaching significantly (P < 0.01) higher concentrations than controls. Further, in the cirrhotic group, the serum concentrations of oestrone sulphate, oestradiol, non-protein bound oestradiol, and non-SHBG bound oestradiol, and the urinary excretion of oestrogen increased significantly (P <0.05). In conclusion, peroral testosterone administration decreases the serum oestradiol/testosterone ratio in patients with normal livers as well as in patients with alcoholic cirrhosis, but the latter group obtains significantly higher oestrogen concentrations.
Prostaglandin F2α and oxytocin release during persistence of the corpus luteum in sheep
Authors: Hooper S. B. , Thorburn G. D.
Published: December 2008

Abstract. Oxytocin (OT), progesterone and prostaglandin F2α (PGF2α) concentrations were measured in the utero-ovarian vein (UOV) of ewes which displayed persistence of the corpus luteum (CL). During the period of expected luteolysis, the frequency of OT and PGF2α pulses in the UOV was significantly (P < 0.005 for both) lower in ewes with persistent CLs, compared with ewes that underwent normal luteal regression. In contrast, the amplitude of both OT and PGF2α pulses was similar in both groups of animals. It is suggested that persistence of the CL resulted from a decreased PGF2α pulse frequency, which may have arisen from a decreased frequency of stimulation by OT. In two persistent CL ewes, however, it appeared that a failure at the level of the uterus may have contributed to the observed decrease in PGF2α release. Although a PGF2α analogue (Lutalyse) infusion into the uterine vein of two ewes with persistent CLs failed to induced luteolysis, it did stimulate a large release of OT into the UOV. This suggests that persistent CLs maybe more resistant to PGF2α and, that at day 22 post-oestrus, these CLs are capable of releasing large quantities of OT into the UOV.
Influence of steroid hormones on the incorporation of amino acids in uterine and cervical tissue of pregnant women
Authors: Wiqvist Ingrid , Linde Anders
Published: December 2008

Abstract. The influence of steroids on protein synthesis in cervical and uterine tissue obtained from early and term pregnant women was studied by measuring the incorporation of labelled amino acids into total protein. It was found that oestradiol-17β and progesterone significantly reduced the incorporation of [3H]proline. Androstenedione and cortisol had no significant effect on the incorporation of [3H]proline even at high concentrations. The protein synthesis inhibitors puromycin and cycloheximide blocked the incorporation of [3H]proline to 80–85%. However, there was no further reduction in the incorporation in the presence of oestradiol. Oestradiol was found to reduce the incorporation of [14C]glycine but not that of [3H]serine. The results indicate that oestradiol and progesterone reduce protein synthesis in human cervical and uterine tissue and that this reduction, at least partially, involves collagen synthesis. Oestradiol and progesterone were equipotent under in vitro experimental conditions. The tissue concentration of progesterone in the pregnant uterus is, however, much higher than that of oestradiol. It seems therefore probable that progesterone rather than oestradiol restricts unopposed synthesis of proteins, presumably mainly collagen.
Thyroid hormone binding and deiodination by pancreatic islets:
Authors: Cortizo A. M. , Chazenbalk G. D. , de Gagliardino E. E. P. , García M. E. , Pisarev M. A. , Gagliardino J. J.
Published: December 2008

Abstract. Thyroxine dehalogenation by rat pancreatic islets was studied incubating isolated islets with labelled T4. [125I]T4 added to the incubation medium was deiodinated by the islets with the consequent production of T3, rT3 and iodide. This deiodination process showed a clear glucose-dependence, being significantly increased in the presence of 16.6 mmol/l glucose. The existence of high and low affinity binding sites for T3 was also demonstrated incubating [125I]T3 with islets under different experimental conditions. The properties of these binding sites were greatly influenced by the extracellular concentration of glucose. Addition of T3 to the incubation medium, significantly modified the insulin release, but its effect varied according to the glucose concentration in the medium, i.e. it enhanced the insulin release at a glucose concentration between 2 to 8 mmol/l; it has no effect at 12 mmol/glucose, and significantly inhibited the secretion of insulin in the presence of 16.6 mmol/l glucose. Our results suggest that thyroid hormones might play a direct regulatory effect on insulin secretion, probably mediated by its deiodination and interaction with specific receptors in the islet cell.
Impaired prolactin responsiveness to a dopamine antagonist in long-term survivors of acute lymphoblastic leukaemia
Authors: Dunkel Leo , Hovi Liisa , Siimes Martti A.
Published: December 2008

Abstract. Cranial irradiation is known to affect the neuroendocrine control of GH secretion. The aim of the present study was to clarify the effect of leukaemia treatment on neuroendocrine control of PRL secretion in long-term survivors of acute lymphoblastic leukaemia (ALL). Pituitary LH, FSH and PRL responses to GnRH and to the dopamine receptor antagonist metoclopramide were evaluated in 18 boys 1.6–9 years after discontinuation of medication for ALL. All the boys had been subjected to prophylactic cranial irradiation and 8 to testicular irradiation. Eight of the boys had supranormal gonadotropin levels either basally or after GnRH. All had normal basal PRL levels, but in 14 of the 18 boys the metoclopramide-releasable PRL levels were subnormal. The decreased PRL responses cannot be explained by the hypergonadotropism, since exaggerated rather than decreased responses are frequently found in patients with primary gonadal failure. We conclude that abnormal regulation of PRL secretion is a frequent consequence of treatment of ALL, probably being due to decreased pituitary lactotrop mass.
A highly sensitive bioassay for PTH using ROS 17/2.8 subclonal cells
Authors: Sato Kanji , Han Doo Chol , Ozawa Minoru , Fujii Yuko , Tsushima Toshio , Shizume Kazuo
Published: December 2008

Abstract. A highly sensitive bioassay for PTH was developed by using rat osteosarcoma cells (ROS 17/2.8). By limiting dilution, ROS cells were subcloned and the subclonal cell line (ROS 17/2.8–5) most responsive to PTH was selected. When subconfluent ROS 17/2.8–5 cells were treated with hydrocortisone for 3 days and then incubated with PTH, the cAMP response was significant at 10–40 ng/l hPTH (1–34) (4 ∼ 16 × 10−12 mol/l). Osteoclast activating factors such as human interleukin I alpha and beta, and tumour necrosis factor alpha did not stimulate cAMP production, whereas a conditioned medium of oesophageal carcinoma cells established from a patient with humoral hypercalcaemia stimulated cAMP production. By selecting PTH-responsive subclonal cells and treating them with hydrocortisone, the sensitivity for detecting PTH was improved approximately 15 times. This method will be useful in the characterization and purification of PTH-like factors produced by malignant tumours from hypercalcaemic patients.
Differential effects of hydrocortisone, fluocortolone, and aldosterone on nocturnal sleep in humans
Authors: Born J. , Zwick A. , Roth G. , Fehm-Wolfsdorf G. , Fehm H. L.
Published: December 2008

Abstract. Previous experiments have suggested that sleep processes are sensitive to influences of corticosteroids. The present experiment was designed to compare effects of three different corticosteroids on human sleep: fluocortolone (a synthetic pure glucocorticoid), cortisol which possesses glucocorticoid and mineralocorticoid activity, and aldosterone (the major mineralocorticoid). Ten male adult subjects were tested in four experimental nights according to a double-blind latinsquare design under conditions of either 1.0 mg of aldosterone, 20 mg of fluocortolone, 80 mg of hydrocortisone, or placebo. Substances were administered orally (fluocortolone, 23.00 h) or infused iv throughout the night (hydrocortisone, aldosterone) starting at 23.00 h. Hydrocortisone and fluocortolone induced a substantial reduction of rapid eye movement sleep. Hydrocortisone increased slow wave sleep activity. No such effect was observed after fluocortolone. Effects on sleep processes of aldosterone, in general, seemed to be neglegible. The results demonstrate differential effects of synthetic glucocorticoid, cortisol, and aldosterone on sleep in humans, which may be attributed to the heterogeneity of corticosteroid receptors in the brain.
Age-related differences in the growth hormone secretory response to hGHRH 1-44 in male rats from infancy through puberty
Authors: Shulman Dorothy I. , Sweetland Margaret , Duckett Gregory , Root Allen W.
Published: December 2008

Abstract. The GH secretory response to varying doses (15, 30, 60 μg/kg) of sc administered hGHRH 1–44 (or normal saline) was measured in vivo in 10, 20, 30, 40, 50, 60 and 130 days old pentobarbital-anaesthetized, male rats. The 10-min GH level and ΔGH were in general significantly greater in older rats (50, 60, 130 days old) than in younger rats (10, 20 days old) following all doses hGHRH. Ten-day-old animals had no significant GH response to any dose of hGHRH tested. ΔGH correlated significantly with age (r = 0.36; P < 0.0001) and Sm-C level (r = 0.29; P < 0.01) but not with serum testosterone concentrations. Monolayer pituitary cell cultures were established in rats aged 10 to 130 days and were incubated with varying concentrations of hGHRH 1–44 (0.05, 0.5, 5.0, 50 nmol/l or incubation medium). Cultures from 10- and 20-day-old animals had a greater percentage increase over basal GH secretion than other groups at all concentrations of hGHRH tested (P < 0.05). Age-related differences in the GH secretory response to hGHRH are present in male rats from 10 to 130 days. The in vitro results reported here suggest that the increase in magnitude and sensitivity of the GH response to hGHRH observed in pubertal animals in vivo under pentobarbital anaesthesia is likely due to influences above the level of the somatotrope receptor.
Ontogenesis of thyroid hormone receptor in foetal lambs
Authors: Ferreiro Beatriz , Bernal Juan , Potter Brian J.
Published: December 2008

Abstract. Affinity and concentration of T3 receptor sites have been measured in nuclear extracts from the brain, lung, and liver of foetal lamb tissues at 50, 82 and 100 days of gestational age. Control experiments indicated that the concentration of sites was similar when nuclear extracts or purified nuclei were used, and that maximal binding capacity was obtained after 2 h of incubation at 22°C. The pattern of receptor binding affinity when different thyroid hormone analogs were used in competition assays with [125I]T3 was T3 > 3,5,3'-triiodothyroacetic acid (Triac) > T4 in the lung and brain. In the liver, Triac had the same affinity as T3. The sedimentation coefficient of the receptor was 3.6 S in lung. There were minor changes of receptor affinity in the brain, but not in the lung or liver, during development with the highest value at 82 days. Receptor concentration increased twice from 50 to 82 days. Since in the brain this is the period of neuroblast proliferation, the results suggest that thyroid hormone is required for proper foetal lamb development and, in particular, for neuroblast proliferation and/or differentiation.
Vasoactive intestinal polypeptide enhances ACTH levels in some patients with adrenocorticotropin - secreting pituitary adenomas
Authors: Ambrosi Bruno , Bochicchio Domenico , Sartorio Alessandro , Morabito Francesco , Faglia Giovanni
Published: December 2008

Abstract. Vasoactive intestinal polypeptide (VIP) was administered (75 μg iv over 12 min) to 14 patients with Cushing's disease, 1 patient with Nelson's syndrome, and 8 normal subjects. VIP induced a significant rise of plasma ACTH levels in 6 patients with Cushing's disease, from a baseline of 13.2 pmol/l (9.9–18.5 pmol/l) to a peak of 24.5 pmol/l (7.7–18.9 pmol/l), median and range (P < 0.05), and in the patient with Nelson's syndrome, from a baseline of 260.9 to 461.3 pmol/l. A significant elevation of cortisol levels was also observed, from a baseline of 567 nmol/l (185–842 nmol/l) to a peak of 727 nmol/l (364–1029 nmol/l); P < 0.05. No modifications in plasma ACTH and cortisol levels were noticed in the other 8 patients with Cushing's disease, or in the normal subjects. In the responsive patients, the median plasma ACTH level reached after VIP was found to be less than that induced by CRH administration. In 2 of the responsive patients, VIP was injected again after successful microadenomectomy and did not then cause changes in ACTH and cortisol concentration. These data demonstrate that VIP specifically stimulates ACTH release in some patients with corticotropinomas but not in normal subjects; the disappearance of such abnormal ACTH responses after successful adenomectomy suggests the presence of specific VIP receptors only on the adenomatous corticotropes.
Lack of desensitization of 3',5'-cyclic AMP response to thyrotropin stimulation in differentiated thyroid carcinoma
Authors: Hamada Noboru , Manabe Yoshitaka , Saito Hifumi , Mimura Takashi , Ito Kunihiko
Published: December 2008

Abstract. The course of the cAMP response to thyrotropin (TSH) in 23 specimens of differentiated thyroid carcinoma and the adjacent normal tissue was studied. In the carcinomatous tissue, the cAMP concentration in slices incubated with TSH was significantly greater after 2 h than after 15 min of incubation; the level was almost the same at both times in normal tissue. The effects of an initial exposure of thyroid slices to TSH (50 U/l on the subsequent cAMP responsiveness to the hormone were investigated in seven more differentiated thyroid carcinomas. In normal tissue, the cAMP level in slices exposed to TSH, washed, and exposed again was lower after the third incubation than in slices exposed to TSH only in the third. In contrast, the cAMP level tended to be greater after the second of 2 TSH incubations in 5 out of the 7 specimens of carcinomatous tissue. The data suggest that differentiated thyroid carcinoma lacks desensitization of the cAMP response to TSH.
Cationized serum albumin enhances basal and stimulated adenylate cyclase activity in canine renal membranes
Authors: Nijs-De Wolf N. , Corvilain J. , Bergmann P. J.
Published: December 2008

Abstract. We examined the effects of cationized serum albumin on the canine renal membrane adenylate cyclase in the basal state and when stimulated with guanylyl-imidodiphosphate, PTH or NaF. Human albumin was cationized to an isoelectric point greater than 9.5 by the addition of hexamethylene diamine. Cationized albumin increased basal and stimulated cAMP production by the membranes and increased the sensitivity of the system to low doses of PTH (0.25 pmol/l), being usually inactive in buffer alone or in human serum albumin. These observations are comparable to those previously reported on thyroid membranes and cells from adrenal tumours and confirm that positively charged macromolecules can increase adenylate cyclase activity. A decrease in non-specific binding of PTH is only partly responsible for the increased sensitivity to the hormone. Though this increase in sensitivity is small, it could nevertheless be useful in the detection of biologically active PTH after extraction from the serum.
The effect of hypermagnesaemia on serum immunoreactive calcitonin levels in normal human subjects
Authors: Suzuki Koyasu , Kono Norio , Onishi Toshio , Tarui Seiichiro
Published: December 2008

Abstract. The effect of hypermagnesaemia on serum levels of immunoreactive calcitonin was studied in normal human subjects. After iv administration of magnesium sulphate over 120 min, the mean (± sem) serum magnesium concentration rose from the baseline level of 0.9 ± 0.1 to 2.6 ± 0.3 mmol/l (P < 0.01), and thereafter remained higher than the baseline level. The magnesium infusion caused a significant increase in serum immunoreactive calcitonin levels (P < 0.01). The rise in serum magnesium concentration was accompanied by a significant decrease in the concentrations of corrected serum calcium and whole blood ionized calcium (P < 0.01, P < 0.01, respectively). Our results suggest that hypermagnesaemia causes an increase in serum immunoreactive calcitonin levels in normal human subjects despite a decrease in the concentrations of corrected serum calcium and whole blood ionized calcium.
Immunocytochemical localization of hFSH as an index of Sertoli cell function in the human testis
Authors: Yoon Doug J. , Golimbu Mircea , Schinella Roger , Stein Bruce , Sklar Charles A. , David Raphael
Published: December 2008

Abstract. The FSH receptor in the human testis has not been well characterized in vivo. Using an immunoperoxidase technique we have attempted the immunocytochemical localization of FSH in testicular tissue from patients with a variety of disorders including oligo- or azoospermia (N = 6), cryptorchidism (N = 3), and prostatic carcinoma (N = 3). Specific staining for hFSH was observed inside the seminiferous tubule, generally near the basal membrane in all except the cryptorchid patients. Specific staining was also localized in the luminal area of the seminiferous tubule. In most cases, FSH-positive cells were also found in the interstitium, with a minority of the cells being macrophages. The latter were more prevalent in the undescended testes and in orchiectomy specimens from patients with prostatic cancer. The pattern of FSH localization observed in this study probably represents receptorbound hormone, and may reflect damage to the Sertoli cell and its tight junctions. Further study of the changes in receptor distribution as an indication of Sertoli cell malfunction, may be helpful in our understanding of human testicular disorders.