bluuebunny/crossref_metadata_2025 huggingface dataset:
Radioimmunoassay for 21-deoxycortisol: clinical applications
Authors: Gueux B. , Fiet J. , Pham-Huu-Trung M. T. , Villette J. M. , Gourmelen M. , Galons H. , Brerault J. L. , Vexiau P. , Julien R.
Published: December 2008

Abstract. A radioimmunoassay for 21-deoxycortisol is described. The immunogen, 21-deoxycortisol-3-(O-carboxymethyl) oxime-bovine serum albumin, was prepared, the antisera raised against it were studied and the reliability of the assay was checked. The antiserum selected cross-reacted with 11-deoxycortisol (0.08%), corticosterone (0.25%), cortisol (0.6%) and 17-hydroxyprogesterone (1.6%). 21-deoxycortisol was separated by celite partition chromatography and eluted in the 70/30 (v/v) isooctane/ethyl acetate fraction together with 11-deoxycortisol and corticosterone.

The radioimmunoassay was used to measure 21-deoxycortisol in the plasma of normal subjects and patients with androgen excess. In normal subjects, men (0.19 ng/ml ± 0.08) and women (0.18 ng/ml ± 0.09) had similar basal levels (mean ± sd). One hour after ACTH stimulation, these levels were increased by a factor of 3.5. In 7 patients treated for classical congenital adrenal hyperplasia associated with 21-hydroxylase deficiency, basal values varied between 9.1 and 39.9 ng/ml (measured at 8 a.m.). In 7 untreated women with lateonset congenital adrenal hyperplasia (with 21-hydroxylase deficiency), ACTH-stimulated levels were increased to between 9 and 25.5 ng/ml. In 14 heterozygous carriers of 21-hydroxylase deficiency, diagnosed by HLA genotyping, all ACTH-stimulated levels were well above the highest corresponding levels in normal subjects, whereas 17-hydroxyprogesterone levels remained within the normal range in 9 of the cases.
Effect of ovine corticotrophin releasing factor, bromocriptine, and dopamine on release of ACTH and β-endorphin in a patient with Cushing's disease
Authors: Nakashima Hiroko , Hirata Yukio , Uchihashi Masahito , Tomita Masahiro , Fujita Takuo
Published: December 2008

Abstract. Release of immunoreactive ACTH and β-endorphin (β-EP) in response to corticotrophin-releasing factor (CRF) and dopaminergic agents was studied in vivo and in vitro in a patient with Cushing's disease. Iv administration of synthetic ovine (o) CRF significantly stimulated plasma ACTH release, accompanied by increase of plasma cortisol levels. Oral administration of bromocriptine significantly suppressed plasma cortisol levels. Although reduced responses of plasma ACTH and cortisol to o-CRF was observed 1 month after removal of the pituitary adenoma, these normalized 6 months after operation. In vitro perifusion of the pituitary adenoma obtained by surgery revealed that o-CRF also stimulated ACTH and β-EP release in a dose-responsive manner (10−9m–10−5 m) and that dopamine suppressed their basal secretion. Gel exclusion chromatography of the perfusates showed that the predominant component of ACTH and β-EP before and after o-CRF stimulation coeluted with standard ACTH and β-EP, respectively. The present data suggest that o-CRF is a potent secretagogue for ACTH and β-EP release from the human pituitary adenoma causing Cushing's disease and that ACTH secretion from certain adenomas, possibly originating from the intermediate lobe of the pituitary gland, is partly regulated by a dopaminergic mechanism.
Functional integrity of anterior pituitary cells separated by a density gradient
Authors: Scheikl-Lenz B. , Markert C. , Sandow J. , Träger L. , Kuhl H.
Published: December 2008

Abstract. Using a continuous Percoll density gradient, endocrine cells of the anterior pituitary were separated. The cells were obtained from adult female Sprague-Dawley rats which had been ovariectomized for 7 days. The gradient revealed two equally sized populations of cells with densities of about 1.02 and 1.09 g/ml. Ninety-two per cent of the cellular GH content, 64% of LH, and 60% of TSH were found in the high density peak. Sixty-one per cent of the cellular Prl appeared in the low density peak. Immunocytochemical staining of the LH containing cells showed that 74% of the gonadotrophs were in the high density peak. After separation, the cells retained their responsiveness to LRH, TRH and GRF. Culture conditions influenced stimulated hormone release. Before stimulation, the cells were cultured either in tissue culture flasks (attached cells) or in Petri dishes (cells in suspension) for 3 days. After TRH-stimulation, suspended thyrotrophs released more TSH than attached thyrotrophs. Comparing the cells of both peaks, attached thyrotrophs of the high density peak showed higher stimulated TSH-release than those of the low density peak. The response of the gonadotrophs and somatotrophs to stimulation did not differ when culture conditions were changed. The present results demonstrate that the secretory activity of endocrine cells is influenced by culture conditions and should be evaluated fore each cell type.
Characterization of microheterogencity of human thyroglobulin from different thyroid disorders
Authors: Gärtner Roland , Bechtner Günther , Greil Walter , Horn Klaus , Pickardt C. Renate
Published: December 2008

Abstract. Human thyroglobulin (Tg) was isolated to apparent purity from various thyroid tissue samples obtained after surgery. Iodine and iodothyronine content of Tg was determined. Isoelectric focussing (IEF) was performed on thin layer agarose gels. Tg revealed a microheterogeneity of 6 bands in the range between pH 4.2 and 4.6. The intensity of the single bands depended on the iodothyronine content of Tg. With increasing degree of iodination, the bands with a lower pI (pI 4.35, 4.40) became more prominent, whereas the bands with higher pI (pI 4.55, 4.60) diminished. This typical change in microheterogeneity pattern could be confirmed by kinetic in vitro iodination and consecutive iodothyronine formation of low iodinated Tg (0.05% iodine). After in vitro desialylation, the bands shifted to a higher pH range (pH 4.60 to pH 4.90), but no reduction of the number of bands occurred. Even in desialylated Tg microheterogeneity is still dependent on iodine content. These results suggest, that the microheterogeneity of Tg is influenced, but not caused by different iodine and NANA content. Different polypeptide composition may be responsible for the microheterogeneity of Tg.

In thyroid diseases without disturbance in Tg synthesis (endemic, diffuse and nodular goitre, Graves' disease) variations in relative intensity of single bands could be related to differences in iodine content. In thyroid cyst fluid and cold nodules in addition to low iodinated Tg, further bands were found with pI-values comparable to desialylated Tg.
Effect of enzyme and enzyme inhibitors on specific binding of hGH to human peripheral lymphocytes
Authors: Kiess W. , Butenandt O.
Published: December 2008

Abstract. A recently described method to investigate growth hormone (GH) receptors on circulating human blood cells has been used to study the effect of a trypsin preparation and antitrypsin moieties on hormone binding to lymphocytes. Trypsinization with one defined dose of trypsin (10 ng/ml) led to a considerable decrease both of specific binding and of binding affinity (affinity constant after 60 min trypsinization 0.5 × 109 vs 1.5 × 109 m−1 in untreated control cells). Exposure of peripheral blood lymphocytes (PBL) to antitrypsin activites was followed by a steady increase of affinity and specific binding (affinity constant: with 10 KIU anti-trypsin 1.9 × 109 m−1, with 100 KIU 2.4 × 109 m−1, with 1000 KIU 3.6 × 109m−1). This antitrypsin effect exceeds the binding values expected after blocking trypsin activities in the incubation medium. In a subset of experiments somatomedin-B (SM-B) was used as the antitrypsin moiety and was shown to increase specific GH binding to PBL in a similar manner as did antitrypsin (with 1000 ng SM-B affinity constant (Ka) 12.0 × 109 m−1, specific binding 9.7% of total radioactivity). It is concluded that enzymatic factors and their inhibitors including partially GH dependent moieties like SM-B modulate specific GH binding to human peripheral lymphocytes in vitro.
Studies on the site of origin and molecular form of the extrahypothalamic corticotrophin-releasing factor (CRF) in rats
Authors: Yasuda Naoki , Yasuda Yuko
Published: December 2008

Abstract. A homologous radioimmunoassay was developed for rat CRF. CRF immunoreactivity was found widely in the extrahypothalamic areas in the rat central nervous system in concentrations 1–3% of that in the median eminence. Large hypothalamic lesions including the paraventricular nucleus and the median eminence did not cause a decrease in the extrahypothalamic CRF concentrations.

CRF of the rat hypothalamus and cerebral cortex both consisted of high and low molecular weight forms. In contrast the posterior pituitary and the spinal cord contained only low molecular weight forms. Upon gel filtration the low molecular weight CRF of the hypothalamus co-eluted with synthetic rat CRF whereas that of the spinal cord was considerably more retarded. The low molecular weight CRF of the posterior pituitary and cerebral cortex was slightly more retarded compared to synthetic rat CRF.

We conclude that CRF in many extrahypothalamic brain areas and the spinal cord does not originate from the hypothalamus and that there is some heterogeneity in the molecular form of the extrahypothalamic CRF.
Temporary increase in the circulating prolactin levels during and after consecutive administration of bromocriptine-mesilate (CB-154) in female mice
Authors: Mori T. , Namiki H. , Niki K. , Satoh K.
Published: December 2008

Abstract. Changes in circulating prolactin (Prl) levels during and after consecutive administration of bromocriptine-mesilate (CB-154; 0.2 mg/day), a potent suppressor of pituitary Prl secretion, were studied in virgin mice of SHN and BALB/c strains. Plasma Prl levels were lower in CB-154-treated SHN mice than in vehicletreated controls until the first week of the daily treatment. However, the circulating Prl increased in the experimental mice and surpassed the control levels thereafter. The elevated levels of Prl were maintained throughout the treatment, then they decreased to control levels 1 month after the termination of the treatment. In BALB/c mice given CB-154, the pattern of changes of the circulating Prl levels was almost the same seen in SHN mice; a significant suppression of the Prl levels was observed on the 2nd day of the treatment and the levels increased and reached to the control levels thereafter. The results have demonstrated that in mice the inhibition of pituitary Prl secretion by CB-154 did not persist throughout the period of consecutive administration.
Thyroid function after resection for non-toxic goitre with special reference to thyroid lymphocytic aggregation and circulating thyroid autoantibodies
Authors: Bang Ulla , Blichert-Toft M. , Petersen P. Hyltoft , Nielsen B. B. ,   Ester Hage, Diederichsen H.
Published: December 2008

Abstract. A series of 91 patients operated on for nontoxic goitre was followed systematically during 24 months post-operatively with regard to thyroid function. A thyroid remnant of at least 5 to 8 g was left in the majority of cases, and thyroid replacement was not given. Histopathological grading was performed on goitrous specimens with reference to lymphocytic infiltration. Thyroglobulin antibodies and thyroid microsomal antibodies were determined pre-operatively. Goitre resection provoked a high, but transient increase in serum thyroid stimulating hormone (TSH) levels with peak values 3 to 6 months after operation. Twenty-four months after surgery serum TSH values had normalized, but were still slightly elevated in patients with bilateral surgery and high lymphocytic infiltration, 9% of the patients. The concentration of serum free thyroxine index (FT4I) and serum total triiodothyronine (TT3) decreased after operation, but within reference range. Twenty-four months after surgery, serum FT4I was back to baseline values, while serum TT3 was still lowered compared to the pre-operative level. None of the patients developed overt hypothyroidism. Occurrence of circulating thyroid autoantibodies was not related to post-operative changes in thyroid parameters. We conclude that thyroid replacement therapy seems not to be indicated routinely following resection for non-toxic goitre, but precaution should be taken in case of bilateral resection and high lymphocytic infiltration of goitrous specimens.
The mechanism of hypocalcaemia following thyroidectomy
Authors: Percival Richard C. , Hargreaves Arthur W. , Kanis John A.
Published: December 2008

Abstract. The mechanism of transient hypocalcaemia following thyroidectomy was studied in 29 consecutive patients undergoing thyroid surgery. Eight of 27 (30%) patients who had a partial thyroidectomy developed transient hypocalcaemia. Hypocalcaemia was attributable to a reduction in renal tubular reabsorption of calcium (P < 0.05), but was not associated with changes in serum values of immunoassayable parathyroid hormone or calcitonin.
High muscle lipoprotein lipase activity in thyrotoxic patients
Authors: Lithell H. , Vessby B. , Selinus I. , Dahlberg P. A.
Published: December 2008

Abstract. Serum lipoprotein metabolism was studied in 7 women before and after treatment for thyrotoxicosis. Of the lipoprotein lipids, the triglyceride concentration in the low density lipoproteins (LDL) (P < 0.01) and the cholesterol concentration in both LDL (P < 0.01) and the high density lipoproteins (HDL) (P < 0.05) increased significantly during treatment. These changes were accompanied by increases in apolipoprotein B (P < 0.01) and A-1 (P < 0.05) concentrations in serum.

Muscle lipoprotein lipase activity (LPLA) was increased in the thyrotoxic state by 46% (P < 0.05) compared with the value after the patients had been rendered euthyroid, but adipose tissue LPLA was only 8% higher (ns) in the former state. The capacity for removal of exogenous fat, as determined by the fractional elimination rate (K2) at an iv fat tolerance test, was 23% higher in the thyrotoxic than in the euthyroid state (ns).

It is suggested that the increase in muscle LPLA in the thyrotoxic state may be due to enhanced sensitivity to catecholamines. This may contribute to the increased capacity for plasma triglyceride turnover in thyrotoxicosis.
Insulin modulates the stimulation of renal 1,25-dihydroxyvitamin D3 production by parathyroid hormone
Authors: Wongsurawat Nirandon , Armbrecht H. James
Published: December 2008

Abstract. Previous studies have shown that there is an impairment in renal production of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), the major biologically active metabolite of vitamin D3, in diabetes. This impairment is not due to a deficiency in the parathyroid hormone (PTH), a major stimulator of renal 1,25(OH)2D3 production. Therefore, we have investigated the capacity of PTH to stimulate 1,25(OH)2D3 production in insulin deficiency and with insulin replacement. Experiments were performed in rats fed a 0.6% calcium, vitamin D sufficient diet for 2 weeks. Thyroparathyroidectomy was performed on all rats. Rats to be rendered diabetic were injected with streptozotocin immediately after surgery. In non-diabetic rats, PTH administration significantly increased renal 1,25(OH)2D3 production (11 ± 2 vs 46 ± 5 pg/min/g; P < 0.05). In diabetic rats, however, PTH caused only a modest increase in 1,25(OH)2D3 production (11 ± 1 vs 19 ± 4 pg/min/g; P < 0.05). With insulin replacement, PTH stimulation of 1,25(OH)2D3 production was markedly increased over that seen in diabetic rats (48 ± 12 vs 19 ± 4 pg/min/g; P < 0.05). PTH was equally effective in raising serum calcium, depressing serum phosphorus and tubular reabsorption of phosphate in non-diabetic as well as in diabetic rats. These results demonstrate that insulin is necessary for the maximal stimulation of renal 1,25(OH)2D3 production by PTH. However, insulin is not necessary for PTH action in terms of renal handling of phosphate and inducing hypercalcaemia. These results suggest multiple pathways for the action of PTH, only some of which are insulin requiring.
Testolactone treatment of precocious puberty in McCune-Albright syndrome
Authors: Foster Carol M. , Pescovitz Ora H. , Comite Florence , Feuillan Penelope , Shawker Thomas , Loriaux D. Lynn , Cutler Gordon B.
Published: December 2008

Abstract. Current medical and surgical therapies of precocious puberty in McCune-Albright syndrome are often unsatisfactory. We used an aromatase inhibitor, testolactone, to treat precocious puberty in a girl with McCune-Albright syndrome. This child was unresponsive to 28 weeks of treatment with the long-acting agonist of LRH, D-trp6-pro9-NEt-LRH. During testolactone therapy, menses ceased, bone age advancement and height velocity diminished, and plasma oestradiol levels were suppressed. Serum gonadotrophin levels remained in the prepubertal range. Testolactone may be an effective therapy of precocious puberty in girls with McCune-Albright syndrome.
DNA and S-phase representation in human growth hormone producing pituitary adenomas
Authors: Hulting A.-L. , Tribukait B. , Bergstrand G. , Werner S.
Published: December 2008

Abstract. The DNA contents of 33 pituitary adenomas from patients with acromegaly were analysed with flowcytofluorometry. Degrees of ploidy and the proliferation rate, expressed as percentage of cells in S-phase, were determined. The aim was to compare these morphological and functional tumour properties with clinical and laboratory parameters to establish a possible relation and to further elucidate the characteristics of these tumours.

In 15 tumours (45%) diploid DNA pattern were found, while 18 (55%) showed varying degrees of aneuploidy. The frequency of cells in S-phase showed wide variations and were equally distributed in diploid and aneuploid tumours. Duration of symptoms, age at diagnosis, preoperative growth hormone (GH)- and prolactin (Prl)-levels, tumour size and grade of invasive tumour growth as determined by radiological estimations, did not correlate to ploidy or grade of proliferation.

The lack of correlation between DNA pattern and proliferation rate in relation to clinical, laboratory and radiological parameters in tumours causing acromegaly contrasts to the documented relation between the degree of ploidy, cells in proliferation and grade of malignancy reported in tumours of other sites. The 55% aneuploid GH producing tumours indicate a certain malignant transformation. The high frequency of cells in S-phase in several GH secreting tumours completes the malignant morphological and functional cell properties. The benign character of tumours causing acromegaly is therefore in contrast to these findings.

The lack of clinical significance of the DNA pattern and the frequency of cells in proliferation in GH producing tumours and the benign character despite malignant cell properties in most of these tumours are difficult to explain. The possibility of unknown factors regulating growth rate, invasiveness and the lack of metastazation in tumours causing acromegaly cannot be excluded.
Persistence of a defective tuberoinfundibular dopaminergic function in rats after long-term removal of oestrogen treatment. An in vivo study
Authors: Cocchi D. , Peñalva A. , Torpia R. , Rossi G. L. , Müller E. E.
Published: December 2008

Abstract. The function of the tuberoinfundibular dopaminergic (TIDA) neurons of 49 rats bearing oestradiolvalerate (EV)-induced prolactin (Prl) secreting tumours (prolactinomas) was evaluated in vivo, 7 months after discontinuation of EV-treatment, with neuroactive drugs acting via stimulation or inhibition of DA neurotransmission. Based on the size and morphologic appearance of the pituitary and on determination of plasma Prl levels, rats previously treated with EV could be divided into those bearing macro- (31/49) and those bearing microprolactinomas (18/49). Administration of the indirect DA agonist drug nomifensine (10 mg/kg iv) lowered plasma Prl levels in control rats, but failed to do so in rats bearing either macro- or microprolactinomas. Administration of the DA receptor antagonist domperidone (50 μg/kg ip) or the synthetic enkephalin analogue FK 33-824 (1 mg/kg ip) failed to induce a rise in plasma Prl in rats with macro-, but induced a clear-cut rise in plasma Prl in those with microprolactinomas.

Prl unresponsiveness to all three neuroactive drugs indicates that long time after EV withdrawal TIDA neuronal function is still highly impaired in rats bearing EVinduced macroprolactinomas. The impairment of TIDA neuronal function would be of lesser extent in rats bearing microprolactinomas as revealed by a defective response to only one of the three applied neuroendocrine probes.
Sexual differences in the effect of serotonin on LH secretion in rats
Authors: Moguilevsky Jaime A. , Faigón María R. , Rubio Modesto C. , Scacchi Pablo , Szwarcfarb Berta
Published: December 2008

Abstract. The effect of 5-hydroxytryptophan (5-HTP), a serotonin (5-HT) precursor, on luteinizing hormone (LH) secretion was studied in prepubertal male and female rats of different ages. In females 5-HTP stimulated LH release on days 16, 18 and 20 but not in older rats (26, 30, 35 days of age). No effects of 5-HTP on LH levels were observed in males. The positive feed-back mechanism of oestrogen-progesterone (E-P), that normally matures in the female between 20 and 26 days, was inhibited by 5-HTP in all the ages studied during prepuberty (26, 30 and 35 days old). On the other hand, in adult ovariectomized rats, 5-HTP administration not only decreased the high LH levels induced by ovariectomy, but the LH release response to E-P as well. These results indicate that there are sexual differences in the effect of 5-HT on LH in prepubertal rats younger than 26 days old.

Administration of p-chloroamphetamine (PCA) a serotonin neurotoxin selective for serotoninergic neurons that depletes 5-HT levels in the brain, induced a significant increase in the LH release response to LRH in females, but had no effect in males. These results, besides suggesting a probable pituitary participation in the 5-HT action on LH secretion in the female, appear to indicate the existence of sexual differences in the effect of 5-HT in adult rats.
Secretory, enzymatic, and morphological characterization of rat pancreatic endocrine tumours induced by streptozotocin and nicotinamide
Authors: Lenzen S. , Klöppel G. , Zielmann S. , Panten U.
Published: December 2008

Abstract. Rat pancreatic endocrine tumours were induced by administration of streptozotocin plus nicotinamide. Fifteen to eighteen months later tumours with wet weights of 0.1 to 224 mg were isolated. These tumours were compared with normal rat pancreatic islets. Insulin release from perifused tumours was stimulated by d-glucose, l-leucine, 2-ketoisocaproate, and d-glyceraldehyde, potentiated by theophylline and inhibited by norepinephrine. Compared with isolated rat pancreatic islets, however, insulin secretory responsiveness to glucose stimulation and insulin content were reduced in tumour tissue. Hypoglycaemia in tumour bearing rats and impaired diffusion of insulin out of the tumours may explain this difference. The pattern of enzyme activities observed in tumour tissue was typical for pancreatic endocrine tissue. The activities of succinate dehydrogenase, the two types of the monoamine oxidase, and α-glucosidase were in the normal range in tumour tissue. Only the activities of 5'nucleotidase and glutamate dehydrogenase were decreased. Immunocytochemical analysis of the tumours revealed that they contained an average of 91% B-cells. In addition 8% of D-cells were encountered. Proportions of A-cells and PP-cells ranged below 1%. Thus this endocrine tumour of the pancreas with a high proportion of functionally intact B-cells is an interesting model for studying regulation of secretion and endocrine tumour development.
'Cryptic' form of congenital adrenal hyperplasia due to 21-hydroxylase deficiency in the Yugoslav population
Authors: Dumić Miro , Brkljačić Ljerka , Mardešić Duško , Plavšić Vesna , Lukenda Milica , Kaštelan Andrija
Published: December 2008

Abstract. Five individuals with the asymptomatic, 'nonclassical', 'cryptic' form of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase (21-OH) deficiency from 5 unrelated families were discovered during hormonal studies and HLA-typing performed in a series of 24 families with CAH due to 21-OH deficiency.

Four of the 5 individuals with the 'cryptic' form of CAH belong to families where the index case was a patient with the classical form of CAH due to 21-OH deficiency. The fifth one originated from a family where the index case was a girl with the 'non-classical', 'late-onset' form of the disease. All the 5 individuals had no clinical symptoms in spite of clearcut biochemical signs of 21-OH deficiency: increased 17-OH-progesterone (17-OHP), dehydroepiandrosterone and androstenedione levels, particularly after ACTH-stimulation. The 17-OHP response upon ACTH stimulation of heterozygotes for this 'non-classical' form of 21-OH deficiency did not differ from the response of heterozygous individuals for the classical form of the disease. The results of this study confirm the hypothesis that individuals with the 'cryptic' form of CAH due to 21-OH deficiency are genetic compounds bearing one allele for the severe, classical form, and on the homologous locus, another one for the mild 'nonclassical' form of CAH due to 21-OH deficiency. Their genotype was 21-OHsevere/21-OHmild, The gene for 'cryptic' 21-OH deficiency, as well as the gene for the classical form of the disease is linked to the HLA system, but in our population apparently it is not in genetic disequilibrium with the antigens B 14 DR 1, as it was shown for other populations studied up to now.
Inhibition of phytohaemagglutinin-induced lymphocyte blastogenesis by serum from pregnant women: correlation between cortisol level and in vitro immunosuppression
Authors: Wajner Moacir , Papiha Surrinder , Arruda Neusa Bianchini
Published: December 2008

Abstract. Peripheral human blood lymphocytes stimulated by optimal doses of phytohaemagglutinin (PHA) were cultured in the presence of serum obtained from non-pregnant (controls) and pregnant women at different stages of gestation. A significant inhibitory influence on cellular growth was identified in the serum from pregnant women from the second trimester onward but more pronounced at the end of gestation. This inhibition was strongly correlated with the levels of cortisol in the sera.

The action of commercial cortisol on lymphocyte reactivity in cultures stimulated by various concentrations of PHA and containing either a pool of pregnancy sera, or a pool of non-pregnancy sera, or a mixture of these pools was also investigated. The hormone provoked a significant inhibition more evident when low doses of PHA were used. The same finding occurred with the gravida's sera pool supplemented cultures.
Body temperature elevation, exercise and serum prolactin concentrations
Authors: Christensen Stig Engkjær , Jørgensen Otto , Møller Jan , Møller Niels , Ørskov Hans
Published: December 2008

Abstract. Ten young healthy normal-weight males were studied in four test situations designed to elucidate the relative role of body temperature increase vs that of exercise per se for pituitary hormone release. Tympanic temperature was recorded continuously during the tests. Elevation of body temperature at rest induced by external heating resulted in parallel changes in serum prolactin (Prl), also found when temperature spontaneously returned towards normal. In contrast, temperature elevation of the same magnitude through exercise (450 kpm/min for 40 min) induced no change in Prl secretion. It is concluded that increase in core temperature is a stimulus of Prl secretion and suggested that exercise apparently inhibits the stimulatory effect.
Serum prolactin levels in women with excessive milk production. Normalization by transitory prolactin inhibition
Authors: Peters F. , Geisthövel F. , Breckwoldt M.
Published: December 2008

Abstract. Serum prolactin levels and milk yield were studied in 27 puerperae with excessive milk production (polygalactia) and compared with 30 normally lactating puerperae. In order to normalize polygalactia, 14 of these women were treated with 2.5 mg bromocriptine per day for 3 days starting on post-partum day 5, 13 women received placebo. Milk flow in polygalactic women started significantly earlier than in puerperae with normal milk yield and developed mean milk volumes of 816 g per day on post-partum day 4. Serum prolactin levels did not differ from levels of puerperae with normal milk yield. There was no correlation between serum prolactin and milk yield. Bromocriptine treatment resulted in a sharp but reversible decline of serum prolactin levels followed by a significant reduction of milk production. Bromocriptine could not be detected in milk specimens, while serum levels showed significant amounts. In placebo treated women prolactin levels and milk yield remained unaffected. These data indicate that serum prolactin concentrations of puerperae with polygalactia are within the normal post-partum range. Short term prolactin suppression by bromocriptine can reduce milk yield, without complete ablactation.
Growth hormone releasing factor induces prolactin secretion in acromegalic patients but not in normal subjects
Authors: Losa Marco , Schopohl Jochen , Müller O. Albrecht , von Werder Klaus
Published: December 2008

Abstract. The effect of an iv injection of growth hormone releasing factor (GRF) on Prl secretion in healthy volunteers and patients with active acromegaly was investigated. Thirteen normal subjects received 100 μg GRF 1-44, and 19 acromegalics received 100 μg GRF 1-44. Nine normals and 9 patients were given the diluent only and served as placebo control. In healthy volunteers GRF did not affect Prl secretion significantly when compared to placebo, whereas in acromegalics Prl levels after GRF were higher than after placebo.

We have divided acromegalics in Prl-responders to GRF (n = 11) and Prl-non-responders (n = 8) using the criterion of strict parallelism between GH and Prl secretion after GRF. In cases with no GH response to GRF a clear increase of Prl levels with the maximum 15–30 min after GRF was also regarded as a Prl response. Acromegalic Prl-responders and Prl-non-responders did not significantly differ in age, sex, previous therapy, and basal GH and Prl levels. However, Prl-non-responders had a significantly reduced response of both GH and Prl to TRH (GH: 147.3 ± 16.0 vs 590.1 ± 127.8%; mean ± se; Prl: 159.4 ± 32.6 vs 504.9 ± 109.3%). It is concluded that 50 or 100 μg GRF does not affect Prl secretion in normal subjects. In contrast, in acromegaly GRF leads to Prl secretion in more than half of all patients.
Thyrotrophin-releasing hormone (TRH) and hormone secretion from the follicular and C-cells of perfused dog thyroid lobes
Authors: Iversen E. , Laurberg P.
Published: December 2008

Abstract. Recently we found small amounts of TRH immunoreactivity in the thyroid gland of dogs and pigs. In the present study we investigated if exogenous TRH influences the release of T4, T3 and cAMP from the follicular cells, and calcitonin and somatostatin from the C-cells of perfused dog thyroid lobes.

10−5 mol/l TRH inhibited the TSH induced iodothyronine and cAMP release from the thyroid while 10−8 mol/l TRH had no effect. The relative proportions of T4 and T3 in thyroid secretion were not altered by TRH infusion. TRH did not influence the basal or the Ca++ induced release of somatostatin and calcitonin.

Hence TRH has a direct inhibitory effect on the hormone secretion from thyroidal follicular cells. This opens the possibility that TRH in the thyroid participate in the regulation of thyroid hormone secretion.

Even though the concentration of TRH found to be effective is high our results may indicate that TRH in the thyroid participates in the regulation of thyroid hormone secretion as an antagonist to TSH.
Immunocytochemical demonstration of oxytocin in bovine ovarian tissues
Authors: Kruip Th. A. M. , Vullings H. G. B. , Schams D. , Jonis J. , Klarenbeek A.
Published: December 2008

Abstract. The presence of oxytocin in ovarian tissue was examined immunocytochemically. Bovine antral follicles and corpora lutea were fixed with glutaraldehyde, picric acid and acetic acid fixative and immuno-stained by the indirect peroxidase-antiperoxydase (PAP) technique. Immunoreactive oxytocin was demonstrated in the granulosa cells of small and large follicles, in the granulosalutein cells of the young corpus luteum and in the large luteal cells of the mature corpus luteum.

The regressing corpus luteum was not stainable. It is discussed that these findings additionally support the view that oxytocin is actually synthesized in ovarian tissues.
Effects of flutamide or of supplementation with testosterone in prepubertal male rats prenatally treated with busulfan
Authors: Viguier-Martinez Marie-Claude , Hochereau-de Reviers Marie-Thérèse , Perreau Christine
Published: December 2008

Abstract. Male rats treated prenatally with busulfan in order to render them aspermatogenic were treated between 23 and 38 days of age either with testosterone, or flutamide. In such aspermatogenic rats, testosterone supplementation stimulated the growth of accessory sex organs, markedly decreased the secretion of gonadotrophins (by 61% for LH and 83% for FSH), decreased testicular weight (–60%) as well as all parameters relating to testicular histology. Flutamide treatment decreased the weight of accessory sex organs, stimulated the secretion of both LH (+200%) and FSH (+63%) by inhibition of the negative feedback of testosterone; endogenous testosterone secretion was increased by 363%. Testicular weight was increased by 44% and the total volume and the cytoplasmic and nuclear area of Leydig cells were increased by 254 and 28%, respectively, but their number per testis was unchanged. The number of Sertoli cells per testis was increased by 49%, but their nuclear area was not modified. In aspermatogenic prepubertal rats, the large increase in plasma FSH demonstrated that FSH release was partly under the control of inhibin, secreted by Sertoli cells when germinal cells were present. Nevertheless, FSH levels after testosterone (inhibition) or flutamide treatment (stimulation) clearly demonstrated that, in the growing rat, FSH secretion is also partly dependent on the negative feedback of testosterone. In the absence of germ cells, FSH was able to re-initiate Sertoli cells mitoses, but not their functional activity. LH secretion was solely controlled by the negative feedback of androgens and, even in the absence of germinal cells, Leydig cells were able to respond to LH stimulation by an increase in testosterone secretion.
Endocrinological and histological changes induced by continuous low dose γ-irradiation of the rat testis
Authors: Pinon-Lataillade G. , Viguier-Martinez M. C. , maas J.
Published: December 2008

Abstract. Young adult Sprague-Dawley rats were continuously whole-body irradiated with γ rays at a dose-rate of 7 cGy/day for 92 days. Plasma LH, FSH and testosterone concentrations and testicular histology were quantified at different times during exposure. Irradiation selectively decreased spermatogonial numbers until 17 days of irradiation, following which a maturation depletion was observed. By the end of the exposure all germ cell types were reduced in number to about 10% of the control values.

No significant changes were found in testosterone concentration nor in the weights of testosterone dependent accessory sex organs, LH plasma concentration increased slightly but not significantly at the end of irradiation. A significant increase in plasma FSH concentration occurred after the numbers of a spermatogonia and preleptotene spermatocytes had been reduced, when number of stage VII pachytene spermatocytes decreased to 36% of control values, whereas numbers of round spermatids and Sertoli cells were respectively 86% and 100% of the control values. These results suggest a possible role of pachytene spermatocytes in the regulation of inhibin production by the testis.
Plasma growth hormone (GH) and somatomedin C response to continuous growth hormone-releasing factor (GRF) infusion in patients with GH deficiency
Authors: Hizuka Naomi , Takano Kazue , Shizume Kazuo , Tanaka Izumi , Honda Noriko , Ling Nicholas C.
Published: December 2008

Abstract. Pituitary growth hormone (GH) responses during a 10-h iv infusion of saline or human GH-releasing factor (hGRF-44) at 500 ng/kg/h, followed by an iv bolus injection of hGRF-44 at 2 μg/kg body weight, were studied in 10 patients with GH deficiency. During saline infusion in 4 patients, small plasma GH increase were observed in 2 patients. However, during hGRF infusion in 6 patients, up to 4 or 13 pulses of GH secretion were observed. The mean integrated GH pulse area during hGRF infusion was 22.5 ± 5.2 (se) ng/ml × h, which was greater than that obtained during saline infusion. Plasma somatomedin C levels did not increase after hGRF infusion. After saline or hGRF infusion all patients responded to an iv bolus injection of the peptide. These results indicate that hGRF infusion augments GH secretion by increasing the number and amplitude of GH pulses and that the infusion does not cause pituitary somatotrophs to lose their capacity to respond to hGRF subsequently.
Antibodies against animal growth hormones appearing in patients treated with human growth hormone: their specificities and influence on growth velocity
Authors: Pérez A. R. , Peña C. , Poskus E. , Paladini A. C. , Domené H. M. , Martínez A. S. , Heinrich J. J.
Published: December 2008

Abstract. The appearance of anti-human growth hormone (hGH) and anti-non-hGHs antibodies in 27 patients with idiopathic hypopituitarism, treated for periods of 6—18 months with three different preparations of hGH, was investigated.

The preparations induced antibodies to GH in 21 out of the 27 patients: 10 patients produced exclusively an anti-non-hGH response, whereas 11 generated both anti-non-hGH and anti-hGH antibodies. The levels of antibodies against hGH had low correlation with decreased growth velocity, whereas those for the antibodies against non-hGHs did not correlate with decreased growth velocity.
Serum somatomedin-C and bioassayable growth-promoting activity (thymidine activity) in appropriate and small-for-gestational-age human newborns
Authors: Thiériot-Prévost G. , Daffos F. , Forestier F.
Published: December 2008

Abstract. The serum level of radioimmunoassayable somatomedin-C and the bioassayable growth-promoting activity evaluated by the stimulating effect of serum upon thymidine incorporation into activated lymphocytes have been measured in the blood of term human foetuses. Comparison between those with a low birth weight and those with normal birth weight has shown that small-forgestational-age subjects have lower somatomedin-C (0.31 ± 0.03 vs 0.52 ± 0.03) and thymidine activity (1.03 ± 0.11 vs 1.50 ± 0.07) (P< 0.001). A positive correlation between somatomedin and thymidine activity was found. There was no difference in serum transferrin levels between both groups. It is suggested that somatomedin, and probably other growth-promoting factors measured by the thymidine bioassay, play a role in regulation of the foetal growth.
Comparison of growth hormone binding and metabolic response in rat adipocytes of epididymal, subcutaneous, and retroperitoneal origin
Authors: LaFranchi Stephen , Hanna Cheryl E. , Torresani Toni , Schoenle Eugen , Illig Ruth
Published: December 2008

Abstract. We undertook a comparison of human growth hormone (hGH) binding and metabolic responses in rat adipocytes of epididymal, subcutaneous, and retroperitoneal origin to determine whether the site of fat depot biopsy might affect the response to hGH stimulation. The results showed highest specific binding in epididymal (3.6%), followed by subcutaneous (2.3%) and retroperitoneal adipocytes (1.5%); half-maximal binding was achieved at 14–18 ng/ml hGH for the three sites. Scatchard analysis of the binding data from each site was linear; there was no significant difference in binding affinities (2.1 to 3.3 × 109, m−1), but the number of binding sites was statiticially higher in epididymal (9.8 × 103) as compared to subcutaneous (7.5 × 103, P < 0.05) and retroperitoneal cells (3.3 × 103, P < 0.01). Stimulation with 5 to 2500 ng pituitary hGH produced a dose-related increase in glucose incorporation, with the largest increase in epididymal fat cells (31%, P <0.05) followed by subcutaneous cells (18%, P < 0.05); no significant increase was seen with retroperitoneal cells. Biosynthetic hGH produced a similar pattern of glucose incorporation in the three sites. Addition of hGH antibodies blocked the glucose incorporation in epididymal adipocytes using both pituitary-derived and biosynthetic hGH. It seems clear that this insulin-like effect is caused by hGH, not an insulin-like impurity. We conclude that the number of binding sites, perhaps related to adipose cell size, differs in adipose tissue from different locations and this influences the metabolic response to hGH stimulation.
Elevated metabolic clearance rate of 1α,25-dihydroxyvitamin D3 in hyperthyroidism
Authors: Karsenty Gérard , Bouchard Philippe , Ulmann André , Schaison Gilbert
Published: December 2008

Abstract. Metabolic clearance rate (MCR) and daily production rate (DPR) of 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) were measured in 7 hyperthyroid patients and 8 control subjects after a single injection of tritiated 1,25(OH)2D3. Using a bicompartmental analysis, MCR of 1,25(OH)2D3 was found to be significantly higher in hyperthyroid than in control subjects (11.5 ± 4.4 vs 5.9 ± 2.4 ml/min (sd), P < 0.01). No significant difference in plasma 1,25(OH)2D and DPR of 1,25(OH)2D3 was demonstrated. MCR was again measured 1 month after initiation of treatment in 4 hyperthyroid patients and remained elevated. In 2 of these patients, MCR was once more determined 6 months later and had declined towards normal. No correlation was found between MCR and DPR and either plasma calcium, phosphate, immunoreactive PTH, 1,25(OH)D and T3 values. In conclusion, MCR of 1,25(OH)2D3 is elevated in hyperthyroidism, but this finding is probably unrelated to the effect of thyroid hormones on bone metabolism.
Altered plasma catecholamines and numbers of α- and β-adrenergic receptors in platelets and leucocytes in hyperthyroid patients normalized under antithyroid treatment
Authors: Ratge Dieter , Hansel-Bessey Sabine , Wisser Hermann
Published: December 2008

Abstract. We measured plasma catecholamines, α- and β-adrenoreceptor numbers and the accumulation of cyclic adenosine monophosphate (cAMP) in the unstimulated state and in response to 10 μmol/l (-) isoproterenol in blood cells from 29 euthyroid controls and from 18 patients with spontaneous hyperthyroidism. In the thyrotoxic patients plasma norepinephrine (1.14 ± 0.5 nmol/l) and epinephrine (0.3 ±0.14 nmol/l) were significantly decreased compared with plasma norepinephrine (1.87 ± 0.7 nmol) and epinephrine (0.41 ± 0.19 nmol/l) in the controls (P < 0.01 and P < 0.05, respectively) and the values obtained in subjects rendered euthyroid by antithyroid treatment (P < 0.001, respectively). α-adrenoceptor density in platelet membranes obtained from patients in the hyperthyroid state (114 ± 38 sites per cell) was significantly decreased when compared with controls (159 ± 48 sites per cell, P < 0.01) and the values from patients under effective antithyroid treatment (136 ± 35 sites per cell, P < 0.01). On the contrary, a significant increase in β-adrenoceptor density in mononuclear leucocyte (MNL) membranes was found in hyperthyroid patients (1751 ± 237 sites/cell) when compared with controls (1510 ± 351 sites/cell, P < 0.05) and the same patients following antithyroid treatment (1455 ± 260 sites/cell, P < 0.001). The equilibrium dissociation constants (KD) did not change in hyperthyroidism. Basal cAMP concentrations in MNL were higher in untreated thyrotoxicosis (45 ± 18 pmol/106 cells/10 min) than in patients in the euthyroid state (35 ± 9 pmol/106 cells/10 min, P < 0.05). Our data support the hypothesis that the balance of α- and β-adrenoceptors depends on the thyroid state. However, before the reputed catecholamine supersensitivity in hyperthyroid man can be accepted, the relationship between alterations in adrenoceptors and the biological responsiveness to catecholamines has to be demonstrated in different human tissues.
Glucagon release and glucose counter-regulation during hypoglycaemia
Authors: Lager Ibe , von Schenck Henning , Smith Ulf
Published: December 2008

Abstract. The importance of a short-term elevation of the ambient glucose level for the release of counter-regulatory hormones and the glucose recovery rate during a subsequent hypoglycaemia was studied in healthy subjects. Hypoglycaemia was induced with insulin infusion after a previous 80 min of euglycaemic (E: 5 mmol/l) or hyperglycaemic (H: 15 mmol/l) glucose clamp. By infusing insulin during the euglycaemic clamp similar levels were reached during both glucose clamps. The same level of hypoglycaemia was reached in both studies (E: 1.5 ± 0.1, H: 1.5 ± 0.2 mmol/l) and the insulin levels were also similar both at glucose nadir and during the recovery period. In spite of this, both the mean glucagon levels at nadir at the mean individual maximal increase were significantly lower after the hyperglycaemic clamp (E: 101 ± 25, H: 54 ± 7 pg/ml, P < 0.05). The glucose recovery rate was also significantly impaired following the hyperglycaemic clamp.

The results show that a short-term elevation of the ambient glucose level impairs the glucagon release during a subsequent hypoglycaemia. This finding may be of importance for the development of the blunted glucagon release in response to low glucose levels in diabetics.
In vitro degradation of angiotensin II (A-II) by human placental subcellular fractions, pregnancy sera and purified placental aminopeptidases
Authors: Mizutani Shigehiko , Akiyama Haruyuki , Kurauchi Osamu , Taira Hiroyuki , Narita Osamu , Tomoda Yutaka
Published: December 2008

Abstract. The degradation of angiotensin II (Asp1-Arg2-Val3-Tyr4-Ile5-His6-Pro7-Phe8: A-II) by human placental particulate and soluble fractions, pregnant and non-pregnant sera, and highly purified placental enzymes such as placental leucine aminopeptidase P-LAP (microsomal), retroplacental serum P-LAP (soluble), aminopeptidase A and post-proline endopeptidase, was studied by measuring liberated amino acids by high performance liquid chromatography. Placental particulate and soluble fractions degraded A-II almost completely into single amino acids. The purified P-LAP (microsomal) actively liberated five amino acids from the N-terminal. The placental particulate fraction containing P-LAP (microsomal) also actively liberated these amino acids. The purified aminopeptidase A liberated Asp1 very actively as expected. When the ratio of the velocity of liberation of each amino acid to P-LAP activity measured with leu-p-nitroanilide as a substrate was calculated, placental soluble fraction liberated Asp1 very actively, but the liberation rate of Asp1 with the purified P-LAP (soluble) was very low. Therefore it seems that the enzyme in the placental soluble fraction and pregnancy serum responsible for the Asp1 liberation is not P-LAP (soluble), but aminopeptidase A. The mixture of purified P-LAP (soluble) and aminopeptidase A showed higher liberation rate of Arg2 and Val3 than that with purified aminopeptidase A alone, demonstrating that once the N-terminal Asp1 was liberated, the P-LAP (soluble) attacks the shorter peptide (angiotension III) very actively. It was concluded that P-LAP (microsomal) together with aminopeptidase A seem to contribute greatly to the degradation of A-II in pregnant women.