bluuebunny/crossref_metadata_2025 huggingface dataset:
Growth hormone secretion in stalk-sectioned rats
Authors: Kamegai Jun , Wakabayashi Ichiji , Sugihara Hitoshi , Minami Shiro , Kitamura Taiko , Yamada Jinzo
Published: June 2009

Idiopathic pituitary GH deficiency appears to result from neonatal disruption of hypophyseal portal vessels in the majority of patients. To examine the mechanism of GH deficiency associated with the disease, the effect of pituitary stalk section on GH secretion was studied in rats. Adult male rats were subjected to stalk section without inserting an impermeable membrane between the cut ends. They were studied 3 to 4 weeks after surgery. In stalk-sectioned rats, pituitary weight, body weight and hypothalamic SRIH content were significantly reduced as compared with sham-operated rats. Hypothalamic GHRH content, plasma T3, T4, corticosterone and testosterone levels, and weights of testes remove and adrenal glands were comparable in the two groups. Plasma GH profiles of sham-operated rats showed characteristic periodic pulses occurring at 2.5-3 h intervals with intervening trough period. In stalk-sectioned rats, plasma GH levels were low with small fluctuations, but GH levels were significantly higher than trough levels of sham-operated rats. The amount of GH secreted during a 6-h period as measured by planimetry was significantly reduced. To ascertain the regeneration of hypophyseal portal vessels, post SRIH rebound in GH secretion, which requires the presence of endogenous GHRH, was examined. Withdrawal of exogenous SRIH infusion triggered a large rebound GH secretion whose magnitude did not differ between groups. In stalk-sectioned rats, GH response to met-enkephalin analogue, FK 33-824, was not observed, whereas prolactin response to the secretagogue was observed in the majority of rats. It appears that in stalksectioned rats, hypophyseal portal circulation is re-established, but GHRH release from the hypothalamus is impaired in the face of sufficient supply of other hypophysiotropic hormones.
Human leukemic T and B lymphoblasts produce insulin-like growth factor binding proteins 2 and 4
Authors: Neely E. Kirk , Smith Stephen D. , Rosenfeld Ron G.
Published: June 2009

The production of insulin-like growth factors and insulin-like growth factor binding proteins by twelve human leukemic lymphoblast cell lines was evaluated by radioimmunoassay, affinity cross-linking, ligand blot, and immunoprecipitation of conditioned media. In all cell lines, detectable IGF-I and IGF-II levels were <0.1 μg/l and <0.3 μg/l, respectively. IGF binding proteins were identified in 6/12 of the lymphoblast cell lines studied. A pair of IGF binding proteins at 31 and 33 kD, immunoprecipitated with an antibody recognizing IGF binding protein 2 but not by an IGF binding protein 3 antibody, was produced by both T and B cells. A 24 kD IGF binding protein, presumably IGF binding protein 4, since it was not recognized by the antibodies for IGF binding proteins 1, 2, and 3, was produced by B cell precursor cells and faintly by one T cell line. These IGF binding proteins were not altered by deglycosylation. Neither IGF binding protein 1 nor IGF binding protein 3 was identified in any of the conditioned media. We speculate that local production of IGF binding proteins 2 and 4 regulates access of the IGFs to lymphoblasts and to hematopoietic precursors in general.
Alterations in the morning plasma levels of hormones and the endocrine responses to bicycle exercise during prolonged strain. The significance of energy and sleep deprivation
Authors: Opstad Per-Kristian
Published: June 2009

The relative significance of physical exercise, energy and sleep deprivation for the morning levels of hormones and the endocrine response to short-term bicycle exercise were investigated in 24 male cadets during a 5-day military training course. Significant increases in the morning levels of noradrenaline, adrenaline, and dopamine, and a decrease in PRL were ascribed mainly to physical strain. Cortisol and hGH increased, whereas insulin and glucose decreased mainly due to energy deficiency. Pulse rate after the bicycle test was unchanged and similar in all groups in spite of increased catecholamine responses. The increased catecholamine response was mainly due to physical strain. The cortisol response to the bicycle test was increased in all groups, and energy deficiency caused slower postexercise recovery. The incremental hGH response to the exercise test was unchanged in the energy-deficient subjects but abolished in the wellfed subjects. The results suggest that the endocrine responses during long-lasting exhausting strain were mainly due to physical exertion and energy deficiency, whereas sleep deprivation did not play any major role.
Postoperative goitre recurrence rate in Turkey
Authors: Ibis Erkan , Erbay Guner , Aras Gulseren , Akin Asim
Published: June 2009

A study was conducted on the incidence of postoperative nontoxic goitre in 206 patients. The mean period of postoperative observation was 7.8 years. The recurrence rate was 30.7% in the 26 patients to whom thyroxine was administered regularly and at doses of 0.15 mg/day or more in the postoperative period, and 46.9% in the 32 patients who received thyroxine regularly at low doses (0.10 mg/day). In contrast, recurrence rate was 71.4% in the 49 patients in whom use of thyroxine was irregular and 81.8% in the 99 patients who received no thyroxine. The recurrence rate was markedly reduced in the patients who used thyroxine regularly at doses of 0.15 mg/day or more as compared with those who used it irregularly or not at all. It was concluded that in Turkey, where iodine deficiency is a major contributory factor of the prevalence of goitre, postoperative administration of thyroxine is necessary in order to reduce the postoperative recurrence rate.
Decreased growth hormone response to growth hormone-releasing hormone in Turner's syndrome: Relation to body weight and adiposity
Authors: Reiter Jean-Claude , Craen Margareta , Van Vliet Guy
Published: June 2009

A decreased growth hormone response to various secretagogues has been described in Turner's syndrome, but the mechanisms responsible for this decrease are unknown. Seventeen prepubertal girls with Turner's syndrome (age 6.4 to 15.7 years; height −0.2 to −5.4 sd, bone age −3.7 to −0.3 sd; weight 93 to 169% of ideal body weight) underwent a stimulation test with GHRH (0.5 μg/kg). Plasma GH and prolactin were measured by radioimmunoassay from −30 to +120 min and insulin-like growth factor-I at time 0. These values were compared with those observed in lean children with constitutional short stature. Peak plasma GH after GHRH was 17.0±3.6 μg/l (mean±sem), significantly lower (p<0.001) than in the short lean children (39.2±5.1 μg/l. In Turner's syndrome patients, the peak GH value was negatively correlated with the percentage of ideal body weight (r=−0.58, p<0.02) and of body fat (r=−0.59, p<0.02). Plasma prolactin levels in Turner's syndrome did not rise after GHRH and showed a normal circadian variation, from 8.0±1.0 μg/l at 08.30 h to 5.0±0.7 μg/l at 11.00 h (mean ±sem). Mean (±sem) baseline plasma insulin-like growth factor-I concentrations was 0.88±0.14 kU/l, higher than in the short lean children (0.49±0.08 kU/l, p<0.05). We conclude that the decreased GH response to GHRH of girls with Turner's syndrome is related, at least in part, to their excess body weight and fat and is associated with higher IGF-I levels than in short lean children.
Octreotide treatment in acromegaly: a comparison between pen-treated and pump-treated patients in a cross-over study
Authors: Roelfsema Ferdinand , Frölich Marijke , de Boer Hans , Harris Alan G.
Published: June 2009

The effect of a schedule of three daily injections of 100 μg octreotide (pen treatment) compared with that of a continuous sc infusion of 300 μg/24 h on GH and IGF-I suppression, and other GH-dependent parameters was studied in 10 acromegalic patients in a cross-over study. Treatment was administered via a specially designed pen or a pump for 4 weeks. Following a washout period of a further 4 weeks, patients were switched to the other mode of delivery. Mean GH levels decreased from 26.2±4.7 to 9.9±3.1 mU/l (p=0.007) during pen therapy and to 7.7±2.4 mU/l (p=0.003) during pump treatment. IGF-I levels decreased from 75.6±9.5 to 42.0±9.3 nmol/l (p=0.003) during pen treatment and to 32.5±2.5 nmol/l (p=0.001) during pump treatment. There was a significant difference in IGF-I levels between pen and pump treatments (p=0.03). In 7 patients the IGF-I levels normalized during pump treatment compared with 3 patients in the pen treatment group. There was no change in the free T4 index levels, but the free T3 index significantly decreased during therapy, without changes in plasma TSH. This study demonstrates that continuous infusion with octreotide results in a better control of GH oversecretion than the intermittent mode of delivery.
Ectopic pituitary transplants restore immunocompetence in Ames dwarf mice
Authors: Esquifino A. I. , Villanúa M. A. , Szary A. , Yau J. , Bartke A.
Published: June 2009

This work was undertaken to study the effects of prolactin on immune function in Ames dwarf mice. For that purpose, adult Ames dwarf mice were implanted with pituitaries from normal mice under the kidney capsule. Ectopic pituitary transplants produced the expected increase in plasma prolactin levels in male and female dwarf mice as compared to sham-operated dwarf or untreated normal mice. Body weight was significantly increased in pituitary-grafted dwarf mice of both sexes, but did not reach the values found in normal (non-dwarf) animals. Pituitary transplants induced an increase in thymus weight and in the number of lymphocytes in the thymus in dwarf mice of both sexes as compared to sham-operated dwarf controls. The weight of the thymus in grafted dwarf mice remained below values found in normal mice, while the number of thymic lymphocytes became indinstinguishable from those recorded in normal mice, Effects of pituitary transplants on the spleen were similar to those described for the thymus; however, neither the weight nor the lymphocyte number in pituitary-grafted dwarfs reached the values found in normal animals. Natural killer activity of spleen lymphocytes from pituitary-grafted male and female dwarf mice was greatly enhanced as compared to lymphocytes from sham-operated dwarfs. This effect was greater in males than in females. The number of white blood cells in pituitary-grafted male dwarf mice was increased and indistinguishable from the values found in normal males. Surprisingly, this effect was absent in the females. These findings suggest that hormones secreted by the transplants, most likely prolactin and growth hormone, can enhance the immune response. This action may be mediated by direct action of prolactin and/or growth hormone on immune cells or by indirect effects.
Human recombinant interleukin 1 inhibits TSH-stimulated morphological changes in thyroid follicles cultured as semi-organs
Authors: Asakawa Hideki , Hanafusa Toshiaki , Oda Yasuo , Katsura Hayato , Miyagawa Jun-ichiro , Mashita Kazuhiko , Kono Norio , Tarui Seiichiro
Published: June 2009

To study the effects of human recombinant interleukin-1 on thyrocytes, we cultured thyroid follicles as semi-organs, each consisting of approximately 10-20 follicles, in the presence or absence of IL-1α or β. Semi-organ culture reproduces the in vivo environment well. After culture for 2 or 4 days, the follicles were incubated with TSH (10 U/I) for 4 h and fixed for light and electron microscopical examinations. Regardless of the presence or absence of IL-1, follicular structure, polarity, and luminal colloid did not change during culture. In thyroid epithelial cells cultured without IL-1, TSH markedly induced elongation of microvilli and formation of reabsorbed colloid droplets. On the other hand, both IL-1α and β inhibited these TSH-stimulated changes. The degree of inhibition correlated with the concentration of exposure to IL-1. We conclude that IL-1 inhibits TSH-stimulated morphological changes in thyroid follicles cultured as semi-organs, depending on the concentration of IL-1.
Equine follicle-stimulating hormone action in cultured Sertoli cells from rat, sheep and pig
Authors: Monet-Kuntz Catherine , Guillou Florian , Fontaine Isabelle , Combarnous Yves
Published: June 2009

Using a suspension of seminiferous tubule cells, we had previously shown that equine FSH is superactive in the male rat, i.e. that it exhibits a higher biological potency than expected from its binding activity. In this work we investigated equine FSH superactivity in rat, pig and sheep, by comparing in each species the equine FSH with the homologous FSH, both for their binding activities (in a radioreceptor assay using a testicular membrane fraction) and for their in vitro biological potencies (in a plasminogen activator assay using a Sertoli cell-enriched population cultured on plastic). In the rat, the binding activity of equine FSH was identical to that of rat FSH, and the biological potency of equine FSH was 47 times higher than that of rat FSH. Hence, superactivity of equine FSH was confirmed in the rat. In the pig, equine FSH was not superactive, since it exhibited binding activity and biological potency identical to those of porcine FSH. In the sheep, the binding activity of equine FSH was 6 times higher than that of ovine FSH, and its biological potency was also higher (14 times). Therefore, equine FSH cannot be considered superactive in this species. In conclusion, equine FSH superactivity is closely related to the species from which Sertoli cells are isolated.
Human endometrial epithelial cells grown on collagen in serum-free medium. Estrogen responsiveness and morphology
Authors: Casslén Bertil G. , Harper Michael J. K.
Published: June 2009

The aim of the study was to explore the possibility of using human endometrial epithelial cells in serum-free culture as a sensitive assay for hormonal effects on the human endometrium. Glands were isolated following enzymatic digestion of the endometrial tissue and plated on a collagen matrix. The epithelial cells were grown in either medium containing serum or in supplemented serum-free medium. No morphologic difference was found between cells grown in these two media for up to 5 days, using either light or scanning electron microscopy. Secretion of prostaglandin F2α (PGF2α) in response to estradiol was not lower in serum-free medium than in medium containing serum for the first 2 days of culture, whereas secretion declined after prolonged incubation in the serum-free medium. This response to estradiol was clearly dose-dependent, and it was further enhanced by addition of arachidonic acid, the precursor for prostaglandin synthesis, to the medium. Co-culture of endometrial stromal cells did not influence the secretion of PGF2α by epithelial cells. We conclude that the secretion of PGF2α from primary cultures of human endometrial epithelial cells grown on collagen in serum-free medium can be used for a limited period as an assay of estrogenic effects on the human endometrium.
Circulating levels of calciotropic hormones during treatment with nasal salmon calcitonin
Authors: Thamsborg Gorm , Storm Tommy L. , Daugaard Henrik , Schifter Søren , Sørensen Ole H.
Published: June 2009

Circulating levels of calciotropic hormones were measured during one year of treatment with either 200 IU of salmon calcitonin daily or placebo as a nasal spray in 20 postmenopausal women with a former Colles' fracture. A supplement of 0.5 gram elemental calcium was given to all participants. Serum levels of parathyroid hormone and human calcitonin were determined with radioimmunoassays, and serum levels of vitamin D metabolites were determined with protein binding assays. We did not find any significant differences between the two groups with respect to serum levels of calciotropic hormones. In the salmon calcitonin treated group there was a tendency towards a small decrease in serum levels of human calcitonin and an increase in serum levels of calcitriol. Our results suggest that treatment with 200 IU of salmon calcitonin daily as a nasal spray does not markedly affect fasting serum levels of parathyroid hormone, human calcitonin, and vitamin D metabolitis.
Spontaneous anovulation causing disappearance of cyclical symptoms in women with the premenstrual syndrome
Authors: Hammarbäk Stefan , Ekholm Ulla-Britt , Bäckström Torbjörn
Published: June 2009

In the premenstrual syndrome the negative symptoms appear during the luteal phase of the menstrual cycle. Ovulation and the formation of a corpus luteum seem to be of great importance in precipitating the syndrome. In a large group of women with premenstrual syndrome investigated daily with symptom ratings and weekly plasma estradiol and progesterone assays, 8 were found to have one ovulatory and one spontaneously occurring anovulatory menstrual cycle. In both these cycles, the post- and premenstrual phases were compared by testing for recurrence of symptoms. All patients showed a highly significant cyclical worsening of negative premenstrual symptoms during the ovulatory cycles, whereas in the anovulatory cycles the cyclical symptoms disappeared, resulting in relief of the premenstrual syndrome. These results support earlier hypotheses, suggesting that the premenstrual syndrome appears as a result of provoking factors produced by the corpus luteum. This view is in line with earlier therapeutic findings showing that induced anovulation can relieve the premenstrual syndrome.
Effect of maternal thyroid autoantibodies and post-partum thyroiditis on the fetus and neonate
Authors: Bech Karine , Hertel Jens , Rasmussen Nini G. , Hegedüs Laszlo , Hornnes Peter J , Feldt-Rasmussen Ulla , Høier-Madsen Mimi
Published: June 2009

Thirty-five pregnant women with thyroid antibodies were followed during pregnancy and 12 month post partum. Twenty antibody-negative women served as controls and none of these developed postpartum thyroiditis in contrast to 12 of 35 antibody-positive women. Umbilical cord blood was collected at birth for measurements of thyroid antibodies, and blood samples for measurements of thyroid hormones were obtained at 5 and 30 days of age in the infants together with a clinical examination. There were no differences between the infants of antibody-positive and -negative mothers or the infants of those who developed postpartum thyroiditis with regard to gestational age at birth, birth weight, birth length or Apgar score, and no difference in thyroid function of the mothers and infants. However, serum TSH level was significantly higher in mothers who subsequently developed postpartum thyroiditis. Furthermore, a significantly lower growth during the first 30 days of life was observed in their infants. Our observations suggest a relationship between the maternal thyroid status in pregnancy and early growth in infancy.
Size heterogeneity of circulating growth hormone in acromegaly. "Big-Big" GH forms are associated with inappropriately low IGF-I levels
Authors: Arosio Maura , Nissim Marina , Ballabio Maria , Orefice Rita , Bazzoni Nicoletta , Faglia Giovanni
Published: June 2009

Circulating GH consists of several molecular size species with different biological activity. A reduced sensitivity of some monoclonal antibodies towards high-molecular weight GH variants has been reported. The aim of the present work was to evaluate the molecular size species of circulating GH using Sephadex G-100 gel filtration chromatography in acromegalic patients and in normal subjects employing both RIA and an immunoradiometric assay for all GH determinations. In 6 normal subjects, studied under GHRH stimulation, little GH was 69.8±6% (mean ±sd), big GH (44 kD) 26.4±6% and big-big GH (>80 kD) 2.8±4%, in IRMA, with a good correspondence with RIA results (70.8±8, 27.0±4, and 3.2±2%, respectively). In 13 untreated acromegalic patients, studied in basal conditions, the little form constituted 76.2±7%, the big form 18.3±4%, which is significantly lower than in normals (p<0.05), and the big-big form 5.5±7%. Similar results were obtained with RIA. A clear elevation of big-big GH (21% for both in IRMA, and 15.7 and 27.8% in RIA) was found in 2 patients with IGF-I levels lower than expected on the basis of mean GH concentrations. The study was extended to an additional acromegalic patient, previously operated and irradiated on, characterized by discrepant serum GH levels in RIA (4.6 μg/l), and in IRMA (1.4 μg/l), and by normal IGF-I levels. Serum GH showed a lack of parallelism to standard GH in RIA, but not in IRMA. RIA immunoreactivity was almost completely composed (92%) of a high molecular weight GH form (>90 kD), not recognized by IRMA. All IRMA immunoreactivity eluted with a Kav corresponding to 19–50 kD. In conclusion: a. the three main molecular size isomers of serum GH are similarly recognized by IRMA and RIA methods in normal subjects. b. in acromegaly, both quantitative and qualitative modifications of the GH chromatographic profile may be present. In particular, increased amounts of big-big forms, whether or not recognized by monoclonal antibodies, have been observed. Their lower bioactivity, suggested by the normal or lower than expected IGF-I levels, can account for the discrepancy between serum GH levels and the clinical picture or IGF-I levels sometimes observed in acromegaly.
Clinical response and prolactin concentration in hyperprolactinemic women during and after treatment for 24 months with the new dopamine agonist, CV 205-502
Authors: Rasmussen Carsten , Brownell Judith , Bergh Torbjörn
Published: June 2009

Twenty-four hyperprolactinemic women of whom 23 previously had been given bromocriptine, were treated between 6 and 24 months with a new non-ergot dopamine agonist, CV 205-502 (quinagolide; Norprolac®, Sandoz Ltd, Basle Switzerland). Twenty-four weeks of treatment resulted in normalization of prolactin secretion in 16 of the 24 women. All of these women as well as 4 of those who remained hyperprolactinemic had regular menstrual bleedings. Fifteen of the 24 women were treated for 24 months and all had normalized prolactin levels in serum at the end of this period. Regular menstrual bleedings were observed in 13 women. Mild to moderate galactorrhea was recorded at baseline in 14 of the 15 women. After 24 months of treatment, mild galactorrhea was still present in 3 women. All 15 women had been treated with bromocriptine or other dopamine agonists before they entered the study. In 9 of the women the tolerability had been judged to be fair (N=4) or poor (N=5). Five of the 15 women had previously discontinued bromocriptine treatment because of adverse effects but had few problems tolerating CV 205-502. Prolactin in serum increased in all the patients after discontinuation of the medication. The results confirm that CV 205-502 seems to be a valuable compound in the management of patients with hyperprolactinemia.
The role of somatostatin and/or dopamine in basal and TRH-stimulated TSH release in food-restricted rats
Authors: Rodriguez Felipe , Jolin Trinidad
Published: June 2009

The present study was carried out to examine the role of endogenous dopamine and somatostatin in the mechanisms involved in the restricted feeding-induced inhibition of TSH secretion in rats. GH secretion was examined in parallel. Restricted feeding by 50% or 75% was associated with a decrease in the pituitary and circulating levels of TSH and GH in both untreated and TRH-treated groups (p<0.001), the changes being proportional to the feeding level. Intravenous injections of the dopamine antagonists, domperidone or haloperidol, failed to affect the magnitude of the differences in plasma TSH and GH levels among control and food-restricted groups, indicating that dopaminergic mechanisms had little effect on the regulation of TSH and GH secretion during restricted feeding in rats. Cerebroventricular injection of somatostatin anti-serum resulted in a marked increase in plasma TSH and GH levels in all the experimental groups (p<0.001). The increase in plasma GH and TSH induced by somatostatin anti-serum was greater in rats fed a 25% diet than in either controls or rats fed 50% of the diet; the values for the latter two groups were also different (p<0.001). The decreased TSH and GH values in somatostatin anti-serum-treated food restricted rats as compared with those in control animals on somatostatin anti-serum or normal rabbit serum can probably be attributed to the decreased available pituitary TSH and GH pools. The data indicate that long-term restricted feeding affects anterior pituitary function in rats, presumably reflecting alterations in the secretion of an inhibiting hormone, somatostatin.
Endothelial cells stimulate proliferation of human thyroid epithelial cells
Authors: Kawakami Atsushi , Eguchi Katsumi , Ida Hiroaki , Kawabe Yojiro , Fukuda Takaaki , Ishimaru Tadayuki , Kurouji Kenichi , Fujita Nagatoshi , Ishikawa Naofumi , Ito Kunihiko , Nagataki Shigenobu
Published: June 2009

The present study was undertaken to investigate cellular interactions between human thyroid epithelial cells (thyrocytes) and endothelial cells. Normal thyrocytes were cultured with either mitomycin C-treated endothelial cells or mitomycin C-treated human foreskin fibroblasts. The proliferative responses of thyrocytes were markedly stimulated by endothelial cells, but not by skin fibroblasts. The proliferative response of the thyrocytes obtained from patients with Graves' disease were similar to that of normal thyrocytes. Furthermore, the cell number of thyrocytes in endothelial cell-thyrocyte co-culture was markedly increased as compared with that in thyrocytes alone. The culture medium of endothelial cells only partly had any effect in the endothelial cell-thyrocyte co-culture experiment. Indomethacin, a cyclooxygenase inhibitor, did not increase the endothelial cells-induced thyrocyte proliferation. Furthermore, the increased proliferative response of thyrocytes stimulated by endothelial cells was not suppressed by heparin. These results suggest that endothelial cells increase thyrocyte proliferation, and that cell contact or extracellular matrix production by endothelial cells may play an important role in the proliferation of thyrocytes.
Effect of insulin-like growth factor 1 on gonadotropin release from the hypothalamus-pituitary axis in vitro
Authors: Kanematsu Toyokazu , Irahara Minoru , Miyake Toshikazu , Shitsukawa Keiji , Aono Toshihiro
Published: June 2009

The effects of insulin-like growth factor-I on gonadotropin release were studied using primary culture of rat anterior pituitary cells incubated with IGF-I (20-5000 μg/l) and a hypothalamus-pituitary perifusion system, in which either the mediobasal hypothalamus-pituitary unit or the pituitary were perifused with IGF-I (20-2000 μg/l). In primary cultures of rat anterior pituitary cells, IGF-I (2000 μg/l) caused a significant increase in the release of both LH (46% increase) and FSH (27% increase). It also caused a significant decrease in the cellular content of LH (9%) and FSH (19%). Its effects in stimulating gonadotropin release were suppressed by administration of anti IGF-I receptor antibody (1 mg/l). In the perifusion system, IGF-I (2000 μg/l) did not affect the LH release from the hypothalamus-pituitary or pituitary alone. However, it caused a significant increase in the GnRH (10−9 mol/l) stimulated LH release from perifused pituitary. These data suggest that IGF-I enhances pituitary gonadotropin release via the IGF-I receptor, but its effect on the hypothalamus was not confirmed.
Chronic hypernatremia due to impaired osmoregulated thirst and vasopressin secretion
Authors: Pearce Simon H. S. , Argent Nicholas B. , Baylis Peter H.
Published: June 2009

We report the case of a young man who became adipsic following a subarachnoid hemorrhage and subsequently had two episodes of life-threatening hypernatremia. Investigations demonstrated that he had defective osmoregulated thirst and AVP release, but normal AVP responses to hypotension and nausea. There is also evidence that he had intact baroregulated thirst. We discuss the results of our investigations in the context of current models of hypothalamic-neurohypophysial function.
Transdermal estrogen replacement does not increase calcitonin secretory reserve in postmenopausal women
Authors: Dick Ian M. , Prince Richard L.
Published: June 2009

The effect of transdermal estrogen replacement on ionized calcium and calcitonin levels was examined in 15 postmenopausal women. Following baseline measurement of calcitonin and ionized calcium in the fasting state, the effect of calcium infusion on calcitonin levels was studied. Estrogen replacement resulted in a fall in baseline ionized calcium, however, the rate of rise of calcium was the same before and after estrogen administration. Thus the time at which a particular calcium concentration was attained was later after the commencement of the calcium infusion following estrogen replacement. Although there was no detectable difference in baseline calcitonin concentrations (pre-estrogen, 2.4±0.4; post-estrogen, 2.1±0.4 pmol/l), following estrogen replacement the time at which a particular calcitonin concentration was attained was later after the commencement of the calcium infusion, reflecting the slower attainment of a particular calcium concentration (p=0.014 by ANOVA). Analysis of total calcitonin production by area under the curve, however, did not show a significant difference before and after estrogen replacement (643 ± 184 and 407±115 pmol·l−1·100 min−1, respectively). When the calcitonin response to calcium infusion was compared at the same calcium concentration, estrogen status had no effect on the relationship. We conclude that transdermal estrogen replacement has no effect on calcitonin secretory reserve in postmenopausal women and does not alter the relationship between elevated calcium and calcitonin levels. We cannot exclude an effect of estrogen on baseline calcitonin levels as the calcium concentration was lower but the calcitonin levels not different.
Plasma concentrations of atrial natriuretic hormone in acromegaly: Relationship to hypertension
Authors: Soszyński Piotr , Slowińska-Srzednicka Jadwiga , Zgliczyński Stefan
Published: June 2009

Atrial natriuretic hormone is involved in the control of blood pressure and water-electrolyte balance. In order to assess the relationship between atrial natriuretic hormone and hypertension in acromegaly, 34 subjects were studied, 18 with acromegaly (10 normotensive and 8 hypertensive) and 16 healthy controls. Plasma atrial natriuretic hormone levels, as well as plasma renin activity, aldosterone and growth hormone levels were measured in basal conditions in all subjects. Additionally, plasma renin activity and aldosterone levels were determined after standard stimulation. In hypertensive acromegalic patients, atrial natriuretic hormone plasma concentrations (39.8±3.5 ng/l) were significantly higher than in patients without hypertension (27.9±4.1 ng/l), and in controls (28.6±1.3 ng/l) (p<0.01 in both comparisons). Stimulated plasma renin activity values were decreased in hypertensive acromegalic patients when compared with those in normotensive patients (1.14±0.29 vs 4.03±0.66 μg·l−1 ·h−1, p<0.01). In acromegaly, atrial natriuretic hormone levels correlated with mean arterial pressure (r=0.58, p=0.01). These results suggest that atrial natriuretic hormone plasma levels are slightly increased in patients with acromegaly and hypertension.
Effect of bromocriptine withdrawal in acromegaly on body composition as assessed by bioelectrical impedance analysis
Authors: Rau Harald , Fischer Harald , Schmidt Kurt , Lembcke Bernhard , Althoff Peter-Henning
Published: June 2009

To evaluate the effect of bromocriptine withdrawal after dopaminergic long-term treatment (15.0±6.8 mg/day, mean ±sd) in 12 acromegalic patients on body composition, bioelectrical impedance was measured before and at the end of two weeks of drug withdrawal. During withdrawal basal hGH and IGF-I increased from 2.5±1.9 μg/l and 2.1±0.8 kU/l to 9.1±11.7 μg/l and 4.9±2.2 kU/l, respectively, and the hGH secretion deteriorated significantly both after oral glucose load and in the TRH test, indicating recurrence of active acromegaly. Reactance and resistance decreased by 5±4 and 23± 19 Ω respectively (p<0.01), whereas body weight remained constant (+0.4±2.1 kg). Bioelectrical impedance analysis indicated evident shifts in body composition, i.e. a significant reduction of body fat (−2.0±1.7 kg) and a simultaneous increase in both lean body mass (+2.4±2.2 kg) and total body water (+1.8± 1.6 l). The changes in body composition were related to a combined effect of unsuppressed hypersomatotropism and the lack of bromocriptine actions other than inhibition of hGH secretion (for example stimulation of the renin-angiotensin-aldosterone system by both the recurred hypersomatotropism and the absence of dopaminergic bromocriptine effects). We conclude that bioelectrical impedance analysis is a good additional tool to assess the pathophysiological effects of bromocriptine withdrawal in long-term treated acromegalic patients.
Follicle-stimulating hormone-dependent estrogen secretion by rat Sertoli cells in vitro: Modulation by calcium
Authors: Talbot J. Alan , Lambert Ann , Mitchell Robert , Grabinski Marek , Anderson David C. , Tsatsoulis Agathocles , Shalet Stephen M. , Robertson William R.
Published: June 2009

We have investigated the role of Ca2+ in the control of FSH-induced estradiol secretion by Sertoli cells isolated from 8-10 days old rats. Exogenous Ca2+ (4-8 mmol/1) inhibited FSH-stimulated E2 secretion such that, with 8 mmol/l Ca2+ and FSH (8 IU/l) E2 secretion decreased from 2091±322 to 1480±84 pmol/l (p<0.002), whilst chelation of Ca2+ in the culture medium with EGTA (3 mmol/l) increased E2 secretion from 360±45 to 1242±133 pmol/l) in the absence of FSH. Further, EGTA (3 mmol/l) markedly potentiated FSH (8 IU/l), forskolin (1 μmol/l) and dibutyryl cAMP (1 mmol/l)-stimulated E2 secretion. Addition of the Ca2+ ionophores, ionomycin (2-5 μmol/l) and A23187 (2 μmol/l), inhibited FSH (8 IU/l)-stimulated E2 secretion by >80%. The effect of ionomycin was totally reversible, whereas that of A23187 was irreversible. Ionomycin (5 μmol/l) had no effect on EGTA-induced E2 secretion in the absence of FSH, but reduced EGTA-provoked E2 secretion by 59% in the presence of FSH (8 IU/l). Similarly, forskolin- and dibutyryl cAMP-provoked E2 production was inhibited 46-50% by ionomycin (5 μmol/l). We conclude that FSH-induced E2 secretion from immature rat Sertoli cells is modulated by intra- and extracellular Ca2+.
Calcitriol decreases calcitonin secretion from a human medullary carcinoma cell line via specific receptor action
Authors: Zabel M. , Dietel M.
Published: June 2009

Since calcitonin stimulates calcitriol production we examined whether a feedback regulatory mechanism exists between these hormones. First, the calcitriol receptor was localized immunocytochemically in cultured TT cells originating from a human thyroid medullary (C-cell) carcinoma. The receptor was demonstrated by light and electron microscopy in cell nuclei and in small amounts in the cytosol. Receptor levels increased when the cells were cultured at physiological (120-240 pmol/l) or somewhat higher concentrations (1200-2400 pmol/l) of calcitriol. In parallel, the same doses of calcitriol markedly inhibited secretion of calcitonin into the medium. These results indicate a feedback loop between calcitriol and calcitonin.
Studies on the effect of prolactin treatment on testicular steroidogenesis and gametogenesis in lithium-treated rats
Authors: Ghosh D. , Biswas N. M. , Ghosh P. K.
Published: June 2009

The effect of PRL supplementation in lithium-treated rats on spermatogenesis, testicular Δ5-3β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase activities, and serum levels of FSH, LH, PRL and testosterone were studied on the 22nd day of the experiment. Subcutaneous injections of lithium chloride at a dose of 2.0 mg·kg−1·day−1 for 21 days resulted in a significant inhibition of spermatogenesis at stage VII of the seminiferous epithelial cycle, along with remarkable diminution of serum levels of the above hormones and suppression of the activities of the above two testicular steroidogenic enzymes. Administration of bovine PRL at a dose of 0.25 mg·kg−1·day−1 plus lithium treatment resulted in a remarkable protection of spermatogenic and steroidogenic activities of the testes, along with restoration of serum levels of FSH and testosterone. It is concluded that PRL can markedly protect the testicular dysfunction induced by lithium chloride treatment in rats.
In vitro evidence for local generation of renin and angiotensin II/III immunoreactivity by the human adrenal gland
Authors: Fallo Francesco , Pistorello Matteo , Pedini Francesco , D'Agostino Domenico , Mantero Franco , Boscaro Marco
Published: June 2009

The adrenal gland of various mammalian species has been shown to contain all the components of a functional renin-angiotensin system. We investigated the existence of this local system in human adrenal tissues surgically obtained. Eight normal adrenals (cortex and medulla) and 6 aldosterone-producing adenomas (aldosteronomas) were examined. Minced tissues were superfused over 270 min, and 15-min fractions were collected. In the perfusates, active renin was measured by immunoradiometric assay with human anti-renin monoclonal antibodies; immunoreactive angiotensin II/III and aldosterone were measured by radioimmunoassay. Adrenal tissues, either normal or pathological, were found concomitantly to release renin, angiotensin II/III and aldosterone. The pattern of this spontaneous release exhibited a pulsatile character. The total amount of renin and angiotensin II/III secreted during superfusion clearly exceeded the tissue content (determined by extraction). Addition of the angiotensin-converting enzyme inhibitor quinaprilat (4×10−5 mol/l) in the superfusion caused a concomitant decrease of angiotensin II/III and aldosterone secretion by 3 normal tissues, and no change in 2 aldosteronomas. These data provide evidence that the human adrenal gland in vitro generates and releases both renin and angiotensin II/III, and support the hypothesis that locally formed angiotensin II/III may play a role as a paracrine regulator of physiological aldosterone secretion.
The relation between pituitary magnetic resonance imaging findings and GH, TSH, PRL dynamics in patients with idiopathic GH deficiency
Authors: Hanew Kunihiko , Utsumi Atsushi , Sugawara Akira , Shimizu Yasuyuki , Tazawa Satoru , Yoshinaga Kaoru
Published: June 2009

The relation between pituitary magnetic resonance imaging (MRI) findings and anterior pituitary function was studied in 36 patients with classic idiopathic GH deficiency. These patients were divided into three groups based on MRI findings which were compared with those of 14 normal short children; i.e. normal stalk (N=6), narrowed stalk (N=20), and transected stalk (N=10). The transected and narrowed stalk groups showed significantly delayed TSH responses to TRH compared with the normal stalk group and with the normal short children. Further, the mean maximal TSH increment in the narrowed and transected stalk group was slightly greater than that in normal short children. In contrast, there were no differences in basal plasma GH and PRL levels and their responses to GHRH and TRH among the three groups. When the patients were divided into normal anterior pituitary and atrophic pituitary groups regardless of stalk changes or when they were divided into groups of stalk changes (narrowing and transection) with and without pituitary atrophy, no differences in GH, TSH and PRL dynamics between the groups were observed. These results indicate that pituitary thyrotrope functions, but not somatotrope and lactotrope functions, in patients with idiopathic GH deficiency are more closely correlated to stalk changes than to anterior pituitary changes observed on MRI.
Middle-aged women with Turner's syndrome. Medical status, hormonal treatment and social life
Authors: Sylvén Lisskulla , Hagenfeldt Kerstin , Bröndum-Nielsen Karen , von Schoultz Bo
Published: June 2009

A study of 49 middle-aged (>35 years old) women with Turner's syndrome was performed to evaluate medical status, hormonal treatment and social life. Most of the women lived a normal social life in stable relationships and all were employed. Some had adopted children and 4 had children of their own. They had all been informed about Turner's syndrome at time of diagnosis, but after the induced puberty they did not know who to turn to with their variety of medical problems. They were healthy except for reduced hearing, which in many cases required hearing aid. Elevated liver enzymes were found in almost all the women. The mechanism behind this finding is unclear, but it does not seem to imply severe liver damage why the indicated estrogen therapy should not be withdrawn from these women. Today amniocentesis and chorionic villus biopsies are commonly used to detect chromosome abnormalities. It is our duty as counsellors to give adequate information on the prognosis of a specific finding in the fetus to help future parents in their decision.
Acromegaly due to ectopic growth hormone-releasing hormone secretion by a bronchial carcinoid tumour. Dynamic hormonal responses to various stimuli
Authors: Glikson Michael , Gil-Ad Irit , Galun Eithan , Dresner Rivka , Zilberman Shalom , Halperin Yizhak , Okon Elimelech , Laron Zvi , Rubinow Alan
Published: June 2009

Ectopic GHRH is a relatively uncommon cause of acromegaly, which should be differentiated from pituitary adenoma, in order to avoid damage to the pituitary gland from unnecessary interventions. We report here on a 66-year-old man with acromegaly due to a GHRH-secreting bronchial carcinoid tumour, who recovered completely following removal of the tumour. His hormonal status was studied before and after the operation. Basal GH, GHRH, IGF-I and PRL levels, as well as plasma GH response to glucose load and TRH administration were abnormal before the operation, and became normal thereafter. The somatostatin analogue SMS 201-995 was found to be a potent inhibitor of the ectopic GHRH and the GH secretion (>500 to 42 ng/l and 15.4 μg/l to 0.8 μg/l, respectively). The effect on GHRH proved to be due to direct effect of somatostatin on the tumour cells, as demonstrated in tissue culture studies. A mixed meal was found immediately to suppress GHRH levels without such an effect on GH secretion. We conclude that the neuroendocrine tests usually practised in acromegaly cannot differentiate between ectopic GHRH secretion and pituitary adenoma. High plasma GHRH levels may serve as a diagnostic test for excessive GHRH production, which is almost always ectopic. These high levels are suppressible by somatostatin and a mixed meal.
Effect of α-adrenergic blockade on pituitary hormonal responses to insulin-induced hypoglycemia in humans
Authors: Fisher B. Miles , Thornton Steve , Hepburn David A. , Morton James J. , Baylis Peter H. , Beastall Graham H. , Gray Christina E. , Frier Brian M.
Published: June 2009

Arginine vasopressin, oxytocin and ACTH are released from the pituitary gland in response to acute hypoglycemia. To investigate the role of α-adrenergic mechanisms in mediating this response, 6 non-diabetic subjects were studied during hypoglycemia induced by 0.15 IU/kg iv insulin under control conditions, and during non-selective α-adrenergic blockade with phentolamine. In the control study plasma arginine vasopressin rose from 1.6±0.8 pmol/l (mean ± sem) basally to a maximum of 2.5±0.8 pmol/l following hypoglycemia (p<0.05). An exaggerated response was found during phentolamine blockade, with a maximum plasma vasopressin of 11.5±0.4 pmol/l (by analysis of variance, p<0.05). The plasma oxytocin response to hypoglycemia was similarily increased during phentolamine compared to control. Plasma growth hormone rose to 94±19 mU/l, and during blockade with phentolamine the response was significantly reduced reaching a peak of 34±7 mU/l (by analysis of variance, p<0.05). ACTH and prolactin both increased in response to hypoglycemia, but the increases were not affected by phentolamine. An α-adrenergic mechanism appears to inhibit the release of arginine vasopressin and oxytocin in response to hypoglycemia, but does not appear to affect the secretion of ACTH.
Prolactinoma and body weight: A retrospective study
Authors: Creemers L. B. , Zelissen P. M. J. , van 't Verlaat J. W. , Koppeschaar H. P. F.
Published: June 2009

Body weight and weight history in association with hormone levels were studied retrospectively in 47 patients with prolactinoma; macroprolactinoma was diagnosed in 36, microprolactinoma in 11 patients. At the time of diagnosis a weight history could be traced in 14 patients, 9 patients having gained weight (11.8± 2 kg), 1 with a weight loss of 5 kg, and 4 reporting unaltered body weight. Body weight and Body Mass Index before treatment were 83±2.4 kg and 27.3±0.6 kg/m2, respectively. In the male patients the prevalence of BMI≥25 was greater than in the average Dutch male population (p<0.001). After 6 months of treatment, mainly with bromocriptine, patients with macroprolactinoma had lost 5.5± 1.6% (p<0.002) of initial body weight. No significant weight change occurred in patients with microprolactinoma. Weight loss did not correlate with degree of hyperprolactinemia, nor with decrease of prolactin levels during treatment, in either group of patients. Thyroid or gonadal function were not associated with weight loss either. It appears that prolactinoma is associated with a higher frequency of overweight, as far as patients with macroprolactinoma are concerned.
Production of a specific polyclonal antibody against the rat β thyroid receptor, using synthetic peptide as antigen
Authors: Puymirat J. , Gadbois P. , Dussault L. , Garceau L. , Dussault J. H.
Published: June 2009

We have developed a polyclonal antibody to a synthetic peptide corresponding to the deduced amino acid residues 67–80 of the amino terminal sequence of the rat thyroid receptor β cDNA. Immunopositive sera were identifed by radioimmunoassay and purified by affinity chromatography. The antibody specifically immunoprecipitated the labelled thyroid receptor β synthetized in vitro but not the rat thyroid receptor α. Furthermore, 38% of the L-T3 binding capacity of the rat liver nuclear receptor were immunoabsorbed by this antibody. By immunocytochemistry, this antibody stained specifically the nuclei of hepatocytes while no staining was observed in the rat testis. This study presents a specific polyclonal antibody against the thyroid receptor β. This antibody will be of a great help in determining the role of the β receptors in the mechanism of action of thyroid hormone.
Biological responses of ICI 164,384 and other anti-estrogens in vaginal and uterine cells of fetal guinea pig in culture
Authors: Chetrite Gérard , Pasqualini Jorge Raul
Published: June 2009

The biological response of the anti-estrogens, ICI 164,384, 4-hydroxytamoxifen and tamoxifen were studied in isolated cells of the vagina and uterus of fetal guinea pig in culture. ICI 164,384 in these two cell lines provokes a significant stimulatory effect on the progesterone receptor levels. This is in opposition to available information where this compound is considered to have full anti-estrogenic properties. At the concentration of 10−8 mol/l ICI 164,384 stimulates progesterone receptor 2-3 times in relation to the non-treated cells. 4-hydroxytamoxifen acts as an agonist in the vaginal cells, but as an antagonist in the uterine cells, in which it can block the stimulatory effect provoked by ICI 164,384. Progesterone, which inhibits progesterone receptor, can block in both cells the stimulatory action of ICI 164,384. No effect of the different compounds tested was found in proliferation or [3H]thymidine incorporation. The agonistic effect of the anti-estrogen ICI 164,384 adds new information about the complexity of the mechanism of antiestrogen action and gives additional models to explore the biological responses of these compounds.