bluuebunny/crossref_metadata_2025 huggingface dataset:
Brown adipose tissue thermogenesis in testosterone-treated rats
Authors: Abelenda María , Nava Maria Paz , Fernández Alberto , Puerta María Luisa
Published: June 2009

The participation of sexual hormones in body weight regulation is partly accomplished by altering food intake. Nonetheless, female sexual hormones also alter brown adipose tissue thermogenesis in females. This study was aimed to find out if male hormones could alter brown adipose tissue thermogenesis in male rats. Testosterone was administered by means of Silastic capsules in adult male rats acclimated either at 28°C (thermoneutrality) or at 6°C (cold), treatment lasting 15 days. Food intake and body weight gain were reduced by hormonal treatment. However, brown adipose tissue mass, protein content, mitochondrial mass and GDP-binding were unchanged at both environmental temperatures. Accordingly, testosterone participation in body weight regulation is thought to be carried out without altering brown adipose tissue thermogenesis. A reduction in the weight of the sex accessory glands was also observed after cold acclimation.
Triiodothyronine (T3) stimulates insulin-like growth factor (IGF)-1 and IGF binding protein (IGFBP)-2 production by rat osteoblasts in vitro
Authors: Schmid Christoph , Schläpfer Irene , Futo Eva , Waldvogel Margaretha , Schwander Jürg , Zapf Jürgen , Froesch E Rudolf
Published: June 2009

Osteoblast-like cells prepared from neonatal rat calvariae and grown under serum-free conditions produce IGF-1 and IGFBPs. In contrast to growth hormone, T3 and PTH increased both IGF-1 mRNA expression and net IGF-1 release in calvaria cells. In addition, they stimulated net production of IGFBP-3 and of an IGFBP with an apparent molecular weight of 32 kDa which was recognized by an antiserum against rat IGFBP-2. Bone cells expressed remarkably high levels of mRNA for IGFBP-2, the predominant IGFBP in serum of newborn rats. T3 at low physiological concentrations but not growth hormone stimulated IGFBP-2 mRNA expression and IGFBP-2 production in bone cells in vitro. Thus, IGFBPs are differentially regulated by these hormones and may play an autocrine/paracrine regulatory role in bone.
Urinary excretion of 19-noraldosterone, 18, 19-dihydroxycorticosterone and 18-hydroxy-19-norcorticosterone in patients with aldosterone-producing adenoma or idiopathic hyperaldosteronism
Authors: Takeda Y , Miyamori I , Iki K , Takeda R , Vecsei P
Published: June 2009

Urinary excretion of 19-noraldosterone. 18, 19-dihydroxycorticosterone (18, 19(OH)2-B), 18-hydroxy-19-norcorticosterone (18-OH-19-nor-B), 18-hydroxycorticosterone (18-OH-B), 18-hydroxycortisol (18-OH-F) and aldosterone were measured in 25 patients with primary aldosteronism, 16 with an aldosterone-producing adenoma and 9 with idiopathic hyperaldosteronism. In patients with idiopathic hyperaldosteronism, urinary 19-noraldosterone (207±51 pmol/day), 18, 19(OH)2-B (21±4.2 nmol/day) and 18-OH-19-nor-B (879±21 3 pmol/day) levels were lower but not significantly different from 19-noraldosterone (263±56 pmol/day), 18, 19(OH)2-B (40±8.7 nmol/day) and 18-OH-19-nor-B (1322±267 pmol/day) seen in patients with aldosterone-producing adenoma. Urinary aldosterone did not differ significantly between patients with idiopathic hyperaldosteronism and those with aldosterone-producing adenoma. Both urinary 18-OH-B and 18-OH-F excretion were significantly higher in aldosterone-producing adenoma (39±5.2 nmol/day, 1660±318 nmol/day, respectively) compared with patients with idiopathic hyperaldosteronism (19±3.3 nmol/day, 541±93 nmol/day. respectively) (p<0.05). Though urinary 18-OH-F and 18-OH-B concentrations were useful markers, the mineralocorticoid steroids which we can only now measure, 19-noraldosterone, 18, 19(OH)2-B and 18-OH-19-nor-B, could not be used to distinguish the two subsets of primary aldosteronism.
Development of Graves' disease after subacute thyroiditis: two unusual cases
Authors: Fukata Shuji , Matsuzuka Fumio , Kobayashi Akira , Hirai Keisuke , Kuma Kanji , Sugawara Masahiro
Published: June 2009

This report describes two unusual cases of subacute thyroiditis from which Graves' disease with hyperthyroidism developed seven to eight years after complete recovery. The first case is a 45-year-old woman who developed hyperthyroidism seven years after recovering from subacute thyroiditis. This patient had a genetic predisposition to both subacute thyroiditis HLA-BW35 and Graves' disease (HLA-BW46). The second case is a 60-year-old woman who developed hyperthyroidism eight years after the episode of subacute thyroiditis; her HLA showed neither BW 35 nor BW 46. It has been reported that if hyperthyroidism is to develop following subacute thyroiditis it occurs within one year. Our observation indicates that it may occur seven or eight years later.
A normal ovulatory woman with hyperprolactinemia: presence of anti-prolactin autoantibody and the regulation of prolactin secretion
Authors: Hattori Naoki , Ikekubo Katsuji , Ishihara Takashi , Moridera Kunisaburo , Hino Megumu , Kurahachi Hiroyuki
Published: June 2009

We present the case of a normal ovulatory woman with marked hyperprolactinemia and no evidence of a pituitary adenoma on CT and MRI. Gel filtration studies showed that most immunoreactive PRL was eluted as 150K–170K macroprolactin. Anti-PRL autoantibody was detected and Scatchard analysis revealed a low-affinity (the association constant: 1.29×107 l/mol), high-capacity (the maximal binding capacity: 1174 μg/l) antibody. Dopamine had little suppressive effect on PRL levels and an anti-dopaminergic agent elicited an augmented response of PRL secretion. These results suggest that the presence of anti-PRL autoantibody may delay the clearance of PRL and/or may alter the central regulation of PRL secretion.
Effect of testosterone on bone mineralization of the hypophosphataemic rat
Authors: Corrêa Pedro HS , Leite Maria OR , Borelli Aurelio , Wajchenberg Bernardo L
Published: June 2009

Clinical observations in patients with X-linked hypophosphataemic rickets, that bone changes can be corrected during puberty, suggest that androgen can participate actively in the process of bone mineralization. In the present study we investigated the role of testosterone on the bone mineralization of male rats placed on a low phosphorus and vitamin D diet and kept in complete darkness after weaning. After 1 5 days the animals presented hypophosphataemia, rickets and osteomalacia, as assessed by histomorphometry of the tibia and seventh caudal vertebra calcification fronts respectively. Testosterone propionate administration for five days, while the animals were kept on the same rachitogenic diet, induced an improvement in the bone mineralization process of the hypophosphataemic rat independently of serum phosphate levels. Testosterone-treated rats were cured of rickets but not of osteomalacia, despite the reduction in osteoid seam area.
Ovarian and circulating levels of oxytocin and arginine vasopressin during the estrous cycle in the rat
Authors: Ho Mei-Ling , Lee Jau-Nan
Published: June 2009

Ovarian extracts of Long-Evans rats separated using high performance liquid chromatography (HPLC) were measured by radioimmunoassays (RIAs) for the presence of oxytocin and arginine vasopressin (AVP). The results showed that the ovary contains both, and that they are indistinguishable from the respective standard synthetic peptides. During the estrous cycle, the ovarian content of oxytocin was 10-fold higher (p<0.01) in estrus than in the other phases, while AVP was 16- and 25-fold higher (p<0.01) in metestrus than in the other phases. In contrast, the plasma levels of oxytocin showed no significant difference among the various phases of the estrous cycle. However, the plasma level of AVP level was significantly higher (p<0.01) in diestrus than in other phases. The present study thus strongly supports the hypothesis that both oxytocin and AVP can be produced by the ovary itself in the rat. The possible roles of oxytocin and AVP in the reproductive cycle are discussed.
Discontinuous and continuous stimulation of FRTL-5 thyroid cells with bTSH cause different cAMP and nuclear proliferation antigen responses
Authors: Klugmann Tobias , Mons Ingrid , Wenzel Björn E
Published: June 2009

Pulsatile TSH secretion has been described in man. We investigated the effect of discontinuous TSH stimulation on FRTL-5 thyroid cells. FRTL-5 monolayers were pulsed with TSH in 4 h incubation periods with alternate 4 h TSH-free intervals, or continuously incubated with TSH. The cAMP production of cells was measured in the supernatant of monolayers. Expression of a nuclear proliferation antigen in FRTL-5 monolayers was determined by a monoclonal antibody (Ki-67) using the alkaline phosphatase-anti-alkaline-phosphatase staining method. The TSH concentration in the stimulation series ranged from 0.01 to 1.0 U/l medium. Rhythmic cAMP production was observed in both discontinuous and continuous stimulation. With discontinuous stimulation cAMP production peaked after about 24 and 48 h, while in the continuous presence of TSH peaks were observed at 32–40 and 48 h. At all TSH concentrations the effect of discontinuous stimulation was higher than in continuously stimulated cultures. The discontinuous incubation stimulated nuclear proliferation antigen expression of FRTL-5 more intensely and there was a positive correlation with TSH concentration. We conclude that the rhythmic pattern of cAMP production after TSH stimulation is independent of the TSH pulse. The amplitude of stimulation and proliferation of FRTL-5, however, is increased by discontinuous TSH application.
Growth hormone secretion in patients with Turner's syndrome as determined by time series analysis
Authors: Wit Jan M , Massarano Albert A , Kamp Gerdine A , Hindmarsh Peter C , van Es An , Brook Charles GD , Preece Michael A , Matthews David R
Published: June 2009

Twenty-four-hour growth hormone (GH) profiles in 26 girls with Turner's syndrome were compared with those of 26 normally growing short children and 24 slowly growing short children. All children were prepubertal and below 12 years of age. A subgroup of 13 girls was treated with ethinyl estradiol and a 24-h GH profile was reassessed. In an additional group of 45 girls with Turner's syndrome (aged 6.7–18.9 years) the effect of age, spontaneous breast development and ethinyl estradiol treatment was studied. The profiles were assessed by Fourier analysis. The oscillatory activity and the mean 24-h GH concentration were similar in children with Turner's syndrome and the normally growing short children, in contrast to lower levels in the slowly growing short children. The periodicity of GH secretion was similar in all groups. In the longitudinal study, ethinyl estradiol treatment resulted in a significant increase in pulse amplitude, but not in periodicity. In the cross-sectional study there was no significant difference between the subgroups of girls with either presence or absence of breast development or ethinyl estradiol treatment. GH secretion was not significantly related to age, height in standard deviation score or height velocity. These data imply that there is no abnormality in GH secretion in girls with Turner's syndrome.
Thyroid hormones and atrial natriuretic hormone secretion: study in hyper- and hypothyroid patients
Authors: Rolandi Ermanno , Santaniello Bruno , Bagnasco Marcello , Cataldi Angelo , Garibaldi Cristina , Franceschini Roberto , Barreca Tommaso
Published: June 2009

Plasma atrial natriuretic hormone (ANH) values were evaluated in 28 hyperthyroid patients and in 11 hypothyroid patients and compared with 20 healthy subjects. In hyperthyroid patients plasma ANH basal levels were significantly (p<0.01) higher (14.2±1.6 pmol/l) than in controls (7.8±0.4 pmol/l) and in hypothyroid patients (6.4±0.3 pmol/l). No significant differences were found between controls and hypothyroid patients. The propranolol-induced decrease in heart rate in hyperthyroid patients did not significantly affect the plasma ANH values. Conversely, after the methimazole-induced euthyroidism a return within the normal range of ANH values was observed. The thyroxine replacement in hypothyroid patients determined a small but significant (p<0.05) increase in plasma ANH values. Observed data suggest that in humans thyroid hormones may influence plasma ANH concentrations independently of their effect on heart rate.
Immunoglobulin G of patients with circumscribed pretibial myxedema of Graves' disease stimulates proteoglycan synthesis in human skin fibroblasts in culture
Authors: Shishiba Yoshimasa , Imai Yumi , Odajima Ritsuko , Ozawa Yasunori , Shimizu Taeko
Published: June 2009

Hyaluronic acid and proteoglycan accumulate in the affected skin of Graves' disease patients with pretibial myxedema (PTM). We aimed to determine whether an autoantibody IgG circulating in PTM patients stimulates proteoglycan synthesis in human skin fibroblasts, resulting in PTM. IgGs were purified from 14 normal subjects, 11 Graves' disease patients with PTM, 5 Graves' disease patients with active ophthalmopathy and 15 Graves' disease patients with neither PTM nor ophthalmopathy. Human skin fibroblasts were incubated with the IgGs and labeled with [35S]sulfate. The medium and cell layer were separated and the proteoglycan was extracted. The 35S radioactivity in the proteoglycan fraction was measured. Compared with normal IgGs or with those of Graves' disease without PTM or ophthalmopathy, PTM IgGs significantly increased the incorporation of the 35S into the proteoglycan. The effect of PTM IgG was dose-dependent. As PTM IgG did not alter degradation of the 35S labeled proteoglycan, an increase in 35S incorporation reflects increased synthesis. The effect was mediated through a mechanism other than adenylate cyclase activation. The present study demonstrates the presence of an autoantibody in PTM IgG that stimulates proteoglycan production through human skin fibroblasts. This is not correlated with the thyroid stimulating antibody activity. It is suggested that the activity of this antibody leads to the development of PTM.
Effect of pancreas transplantation on decreased levels of circulating bone γ-carboxyglutamic acid-containing protein and osteopenia in rats with streptozotocin-induced diabetes
Authors: Ishida Hitoshi , Seino Yutaka , Takeshita Noritaka , Kurose Takeshi , Tsuji Kazuo , Okamoto Yoshimasa , Someya Yoshimichi , Hara Kuniko , Akiyama Yasuhiro , Imura Hiroo , Nozawa Masumi
Published: June 2009

Diabetic osteopenia has been known as one of the chronic complications of diabetes mellitus, and a decrease in bone turnover has been thought to be one of the pathophysiological characteristics of this complication. In order to investigate the effect of long-term insulin therapy on low bone turnover in diabetes, pancreas transplantation was performed on streptozotocin-induced diabetic rats. Plasma levels of bone γ-carboxyglutamic acid-containing protein(osteocalcin) in untreated diabetic rats were 0.9±0.1 (mean±sem) nmol/l, significantly lower than the value of 4.2±0.6 nmol/l in control rats (p<0.01). Pancreas transplantation reversed this decrease to 6.3±1.1 nmol/l, which was not significantly different from the value in control rats. The circulating levels of calcitriol were significantly decreased in the untreated diabetic group (p<0.01), and the decrease was fully reversed by pancreas transplantation. In addition, the decreases in bone length, strength and weight were also improved by the transplantation. This evidence clearly shows that the improvement of metabolic derangements in diabetes by insulin is essential for the prevention of deterioration in diabetic osteopenia. It is possible, therefore, that insulin exerts an indirect beneficial influence through the metabolic amelioration on the decreases in bone turnover and circulating osteocalcin in diabetes mellitus, or has a direct stimulatory effect on the osteoblasts via the insulin receptor since its presence has been shown recently in osteoblastic cells.
The role of maternal thyroid hormones in maintaining early pregnancy in threatened abortion
Authors: Maruo Takeshi , Katayama Kazuaki , Matuso Hiroya , Anwar Mochamad , Mochizuki Matsuto
Published: June 2009

To evaluate a possible role of thyroid hormones in maintaining early pregnancy, serum levels of thyroid hormones, TSH and thyroxine-binding globulin (TBG) in 32 patients with a clinical diagnosis of threatened abortion were compared between two groups of patients with favorable and unfavorable pregnancy outcome. Serum levels of T4, T3, free T4 and free T3 levels determined at the onset of clinical signs of threatened abortion were found to be significantly lower in patients (N = 11) who subsequently aborted compared to patients (N = 21) who did not. Serum TSH levels did not differ between the two groups. Serum TBG levels in the patients who subsequently aborted were lower compared to patients with favorable pregnancy outcome. Furthermore, serum levels of T4 and T3 at the onset of threatened abortion in patients who subsequently did not abort were significantly higher compared to levels before pregnancy, whereas little increase in serum T4 and T3 levels relative to the prepregnant levels was observed at the onset of clinical signs in the patients who subsequently aborted. These data imply a possible role of thyroid hormones in maintaining early pregnancy, and suggest that maternal serum level of thyroid hormone may be one of the endocrine factors responsible for the outcome of threatened abortion.
Role of ovarian sex steroids in the regulation of thyrotropin (TSH) secretion of hypogonadal women
Authors: Rossmanith Winfried G , Stäbler Claudia , Benz Reiner , Bornstein Stefan R , Scherbaum Werner A
Published: June 2009

The exact role of ovarian sex steroids in the neuroendocrine regulation of thyrotropin (TSH) release in women can only be accurately assessed in the absence of any considerable ovarian sex steroid feedback upon the hypothalamic-pituitary unit. Consequently, the unstimulated episodic and thyrotropin-releasing hormone (TRH) stimulated TSH secretion was evaluated in postmenopausal women before and during sequential ovarian sex steroid replacements. Seven euthyroid women (mean age: 59.4 years) were studied initially without any sex steroid replacement (control studies), then on the last day of a 21-day course of oral estradiol-valeriate (E2) administration (2 mg daily) and finally, on the last day of a 21-day course of oral estradiol-progesterone (E2/P4) replacement (2 mg E2 and 200mg micronized P4 daily). During all study occasions, blood was sampled at 10 min intervals for 10 h, while TRH (200 μg iv) was administered 8 h after initiation of blood collections. Compared to the control conditions, serum E2 and P4 concentrations markedly increased (p< 0.001) following oral E2 or E2/P4 treatments. Total triiodothyronine (T3) and thyroxine (T4) concentrations and free T3 and T4 equivalents remained unchanged during E2 and E2/P4 regimens. In the unstimulated secretory profiles, TSH was found to be episodically released, with little interindividual variability for each study condition. Since the TSH pulse attributes (pulse amplitudes, frequencies, interpulse intervals, mean TSH concentrations, by Cluster pulse algorithm) did not significantly change during E2 and E2/P4 replacements, the episodic character of TSH secretion virtually remained unchanged by sex steroid replacements. In addition, the TRH-stimulated TSH releases during E2 and E2/P4 replacement therapies closely resembled those during control conditions. These observations demonstrate that both the unstimulated episodic and TRH-stimulated TSH secretion are unaffected by ovarian sex steroid replacement in hypogonadal women. Collectively, our findings suggest that ovarian sex steroids may not be critically involved in the neuroendocrine regulation of TSH secretion in women.
Human placental lactogen inhibits growth without changing serum levels of IGF-1 in rats: an apparent specific action of the hormone
Authors: Chiang Mimi H , Nicoll Charles S
Published: June 2009

Previous work in our laboratory has shown that the internal environment of rats has reduced growth-promoting activity during the second half of gestation and this condition is associated with resistance to the anabolic effects of GH. The placenta appears to be responsible for this condition but injections of estradiol plus progesterone into virgin females did not mimic it. Accordingly, it seemed worthwhile to test the effects of a placental lactogen (PL) for possible growth inhibitory effects. In the present study the effects of human (h)PL on skeletal growth in young female rats and on the growth of embryonic tissue transplants under their kidney capsules were investigated. Human (h) and bovine (b) GH, and ovine prolactin (oPRL) were also tested to determine whether the results obtained with hPL were specific. Twice daily subcutaneous injections of a high dose of hPL (10mg/day), but not of oPRL (5 mg/day) for 7 days inhibited both host tail growth and tibial epiphyseal plate width, and growth of whole 10-day embryo transplants. Injections of hGH at 1 mg/day for 8 days significantly increased host skeletal growth and growth of 12-day embryonic head transplants; at the same dose, neither bGH nor oPRL affected growth of the embryonic heads or of the host tibial epiphyseal plate width, but the bGH increased host tail growth. By contrast, the 1 mg/day dose of hPL significantly reduced the host's tibial epiphyseal plate width, tail growth, and transplant growth; lower doses of hPL (10 and 100 μg/day) were also inhibitory. Although all the hormone treatments increased total serum IGF-1 levels in the females, none of them had a significant effect when compared to saline injected control animals. Thus, the growth-inhibitory effects of hPL treatment appear to be specific to that hormone and they are not mediated by depression of serum IGF-1 levels. If these effects of hPL are mimicked by one or more of the rodent PLs, then the reduced growth-promoting activity and resistance to GH action that occurs in pregnant rats could be due to the rat PLs. These results indicate that in addition to having glucose-sparing effects in the mother, PLs could promote fetal growth by inhibiting growth of maternal tissues, which would thus spare other metabolites, such as amino acids and vitamins, for the conceptus.
Increase in the expression of thyroid hormone receptors in porcine granulosa cells early in follicular maturation
Authors: Maruo Takeshi , Hiramatsu Shinsuke , Otani Tetsuo , Hayashi Masato , Mochizuki Matsuto
Published: June 2009

Thyroid hormone has been demonstrated to synergize with FSH to exert stimulatory effects on the differentiation of porcine granulosa cells. In order to further characterize the nature of thyroid hormone action on granulosa cells, the presence of triiodothyronine (T3) receptors in the nuclei of porcine granulosa cells was examined, and qualitatively and quantitatively compared during follicular maturation. Then, comparative abilities of granulosa cells from varying follicle stages to respond to T3 were assessed in terms of FSH-induced LH/hCG receptor formation and progesterone secretion. Furthermore, the expression of erb-A was analyzed using Northern blot hybridization of porcine granulosa cell RNA with a v-erb-A probe. Binding experiments with [125I] T3 showed that granulosa cell nuclei obtained from small follicles had a greater ability to bind [125I] T3 compared to those from large follicles. Scatchard analysis revealed the presence of nuclear T3 receptors with a single class of binding sites. There was little difference in the affinity of the T3 receptors during follicular maturation. By contrast, the number of the T3 receptors was higher in small follicle granulosa cells compared to that in large follicle granulosa cells. Thus, the increased T3 binding to small follicle granulosa cells relative to large follicle granulosa cells appears to be attributable to the increased number of the nuclear T3 receptors rather than to a change in the affinity. The magnitude of the stimulatory effects of T3 on granulosa cell functions was maximal in small follicle granulosa cells, but negligible in large follicle granulosa cells. Northern blot analysis revealed that granulosa cell RNA contains erb-A transcripts of 5.0 kb and 2.7 kb and that the erb-A transcript abundance is higher in small follicle granulosa cells than that in large follicle granulosa cells. The increased expression of erb-A in immature granulosa cells may be responsible for an increase in the number of T3 receptors in less mature granulosa cells. These results suggest that thyroid hormone acts via its nuclear receptors selectively in immature granulosa cells early in follicular maturation to amplify the FSH actions in the facilitation of granulosa cell differentiation.
The appearance in thyroidectomized mice of immunoglobulins that bind TSH and stimulate FRTL-5 thyrocytes
Authors: Gafny Mira , Ben-David Chava , Sirkis Nava , Gordon Amirav , Gross Jack
Published: June 2009

The purpose of these studies was to examine whether thyroid stimulating antibodies in Graves' patients could arise as auto-antiidiotypic antibodies to endogenous anti-TSH antibodies. The model system chosen was the thyroidectomized mouse, exhibiting an elevated level of endogenous, circulating TSH. Mice were thyroidectomized by 131I administration. Sera samples were drawn 1 to 14 months later. The following activities were measured in the immunoglobulin (Ig) fractions prepared: (a) TSH binding by elisa techniques, (b) iodide pump activity (as measured by 99mTcO4 uptake) and (c) increased [3H]thymidine incorporation into the DNA of FRTL-5 cells. TSH binding Igs were detected in 29/98 mice thyroidectomized for 7–14 months. Stimulation of technetium uptake was observed in 59/110 mice and stimulated labeled thymidine uptake in 37/102 mice, beginning eight and nine months after thyroidectomy, respectively. Of the positive animals, 51 showed a single stimulating activity. The incidence and the serum titers of Igs that stimulate technetium uptake increased significantly with time. Indeed, in the group tested 14 months post-thyroidectomy, 75% of the sera were positive for this antibody with a mean titer eightfold higher than the controls. Hybridomas were prepared from the spleen lymphocytes of thyroidectomized mice. Of these, 18 produced 99mTcO4 uptake stimulating Igs, 12 [3H]thymidine-uptake stimulating Igs and 18 TSH binding Igs. Most of the hybridomas secreted Igs with a single bioactivity. One monoclonal antibody was isolated which neutralized the bioactivity of bTSH on FRTL-5 cells. 99mTcO4 uptake was decreased by 50% and [3H]thymidine uptake was virtually abolished. These results suggest that the hypothyroid mouse can develop anti-TSH antibodies and thyroid-stimulating antiidiotypic antibodies by an autoimmune process.
Patterns of ovulation, conception and pre-implantation embryo development during the breeding season in rhesus monkeys kept under semi-natural conditions
Authors: Ghosh Debabrata , Sengupta Jayasree
Published: June 2009

The occurrence of ovulation and conception in the female rhesus monkey (Macaca mulatta) under natural conditions is seasonal and maximum during the months of October to March. Such seasonality in reproduction suggests dependence on environmental factors like photoperiod, temperature and rainfall. There occur significant fluctuations in these environmental factors also during the breeding season itself. Whether there occur any discernible changes in the occurrence of ovulation and conception, and in the incidence of abnormality in pre-implantation stage embryo development in the rhesus monkey, associated with changes in environmental factors within the breeding season has not been known and was investigated in the present study using a total of 304 menstrual cycles over a period of five years. No preferential sidedness for any ovary to ovulate more was evident, the frequency ratio of ovulations in left ovary to right ovary being 1.02. Despite the absence of any pattern in the side selection of ovulations in successive cycles, the chance of ovulations in alternate ovaries for successive cycles appeared more likely (67% cases). An average of 21% of menstrual cycles were found to be non-ovulatory with significantly higher menstrual cycle lengths (p<0.03) compared with that of ovulatory cycles. An additional 28% of the mated, conception cycles yielded degenerated or desynchronized pre-implantation stage embryos. Furthermore, the number of non-ovulatory cycles (p<0.05) and the incidence of abnormality in pre-implantation stage embryos (p<0.02) were higher during the months of transition in (October) and out (March) of the breeding season. It has been suggested that an integrated influence of environmental factors, mainly photoperiod and temperature, induces adjustments in the function of the hypothalamus-pituitary and the ovarian axis and during transitional months of the breeding season it becomes more vulnerable to be desynchronized, thus resulting in disturbances in the follicular maturation, ovulation and oocyte presentation.
Effect of estradiol and progesterone on myometrial LH/hCG receptors in pigs
Authors: Ziecik Adam J , Jedlinska Maria , Rzucidlo Slawomir J
Published: June 2009

High affinity luteinizing hormone/human chorionic gonadotropin (LH/hCG) receptors have been identified in porcine, rabbit and rat uteri and immunocytochemically demonstrated in the human uterus. We have now assessed the effect of estradiol and progesterone on the capacity and affinity of LH/hCG binding sites in crude membrane fractions of porcine myometria. Nineteen cross-bred gilts were ovariectomized at 6–7 months of age. Five weeks later, the experiment was conducted and gilts were given estradiol benzoate 2 mg (N= 5), progesterone 50mg (N=4) and 2 mg of estradiol benzoate plus 50 mg of progesterone in 2 ml of corn oil (N = 6), im for five consecutive days. Controls (N = 4) received 2 ml of the vehicle. Gilts were hysterectomized 24 h after the last injection. Blood samples for assays of LH, estradiol and progesterone were collected 1 h before hysterectomy. The numbers and affinities of unoccupied LH/hCG binding sites were characterized in all samples of myometrium. The results indicate that treatment with estradiol benzoate increases (p <0.01) the number of LH/hCG binding sites compared with gilts receiving corn oil. Progesterone treatment caused elevation in the number of LH/hCG receptors (p<0.05), when compared with estradiol alone (2.9±0.3 vs 1.2±0.1 fmol/mg protein, respectively). Combined administration of estradiol and progesterone increased receptor capacity to 2.7±0.4. Steroid treatment did not alter the affinity (Ka) of [125I]hCG binding to receptors and it varied from 1.8±0.8 to 2.9±0.2 ×1011 l/mol. Concentrations of LH (pmol/l) were maintained at high (64.3±14.3), medium (28.6±10.7), and low (10.7±3.6) levels in control, progesterone and both estradiol and estradiol plus progesterone treated groups, respectively. These results indicate that estradiol and progesterone independently stimulate the appearance of unoccupied LH/hCG receptors in the porcine myometrium.
In vitro effects of tumor necrosis factor-α on human thyroid follicular cells
Authors: Deuss Ulrich , Buscema Massimo , Schumacher Heike , Winkelmann Werner
Published: June 2009

Tumor necrosis factor-α is assumed to be an important mediator in thyroid autoimmunity. In the present study we have shown that human thyrocytes possess a single specific binding site for recombinant tumor necrosis factor-α with an average of 9,300 receptors/cell (Kd = 1.9 · 10−10 mol). The effects of the cytokine on thyroid cell proliferation were assessed by 3H-thymidine uptake as well as by the protein and DNA content of cell monolayers. Low dose tumor necrosis factor-α resulted in a moderate stimulation of cell proliferation with an increase of 3H-thymidine incorporation from 44,613±7,989 cpm under basal conditions to 63,326±6,822 cpm after 100 U/l tumor necrosis factor-α (p <0.01). Higher doses of the cytokine were less effective. On average, bTSH stimulated cAMP production of human thyrocytes was significantly augmented after preincubation with recombinant tumor necrosis factor-α. The maximum effect was observed after 1,000 U/l tumor necrosis factor-α (281.5±107.0 vs 114.5±33.6 fmol cAMP/μg protein under basal conditions; p<0.05), whereas higher doses of the cytokine were again less effective. This phenomenon could at least partly be explained by a cytokine-mediated downregulation of tumor necrosis factor-α binding. We conclude that in vitro tumor necrosis factor-α modulates in addition to its well known synergistic effect on interferon-γ induced HLA class II expression the function and proliferation of human thyroid follicular cells as well. These effects are mediated via specific cell surface receptors.
Body weight and/or endogenous estradiol as determinants of cortical bone mass and bone loss in healthy early postmenopausal women
Authors: van Beresteijn Emerentia CH , van Laarhoven Jan PRM , Smals Anthony GH
Published: June 2009

The objective was to study the independent relationships of body mass index and endogenous estradiol to cortical bone mineral density and the rate of cortical bone loss at the radius in healthy early postmenopausal women. Fifty-one healthy early postmenopausal women (aged 58–66 years) participated. The women were a subset of a population participating in a 10-year longitudinal study to elucidate the influence of dietary calcium on the rate of cortical bone loss. Cortical bone mineral density at the radius, body weight and body height were measured annually (1979–89). Concentrations of sex steroids were measured in serum samples collected during the last year of follow-up (1989). Endogenous estradiol levels, although significantly positively correlated with body mass index, were not independently related to bone mass indices of the radius. Body mass index, on the other hand, was found to be positively related to cortical bone mineral density and negatively to the rate of bone loss, even after adjustments had been made for confounding factors. Our results suggest that the level of total estradiol is not an important determinant of cortical bone mass indices in healthy early postmenopausal women. Other factors of overweight such as mechanical loading may be important.
Effects of wheat bran on blood and tissue hormone levels in adult female rats
Authors: Arts Cor JM , Thijssen Jos HH
Published: June 2009

The protective effect of dietary fiber on breast cancer development might be explained by the interaction between dietary fiber and hormonal processes. We studied the effects of dietary fiber and the effects of a reduced energy intake on the exposure of mammary tissue to both estrogens and progesterone, as well as the blood plasma levels of these steroids and of LH and FSH. Adult female Fisher rats were fed ad libitum either a low-fiber diet (0.5% dietary fiber based on wheat flour) or a high-fiber diet (9.2% dietary fiber based on wheat bran). A third group was used to control for the reduced energy intake of the high-fiber group and was fed the low-fiber diet restricted. Energy intake was similar for the second and third groups. Four out of 14 rats of the high-fiber group and 4 out of 15 rats of the restricted low-fiber groups were not in cycle after seven weeks on the experimental diets, indicating that the estrous cycle was significantly affected by a reduced energy intake. Exposure of mammary tissue to estrogens did not differ among the groups, as measured by estrone, estradiol-17β, estriol and peroxidase activity. During the peak period, plasma LH levels were significantly higher in the high-fiber group than in the two low-fiber groups. FSH and progesterone plasma levels were unaffected by the experimental diets. It is concluded that dietary fiber affects the hormonal processes involved in breast cancer development. The increased LH levels indicate an increased estrogen production in the ad libitum high-fiber group.
Multihormonal response to corticotropin-releasing hormone in inferior petrosal sinus blood of one patient with Cushing's disease: comparison with in vitro secretion of the tumoral corticotropes
Authors: Tabarin Antoine , Corcuff Jean-Benoît , Rashedi Michel , Angibeau Reine , Caille Jean-Marie , Ducassou Dominique , Dufy Bernard , Roger Patrick
Published: June 2009

A multihormonal response to CRH during inferior petrosal sinus sampling in patients with Cushing's disease has recently been described. Whether it reflects multihormonal secretion by the corticotropic adenoma, or secretion by non-tumorous adjacent cells via paracrine mechanisms remains debatable. We have compared the effect of CRH on ACTH, GH, PRL and TSH secretion during inferior petrosal sinus sampling with its effect on the in vitro secretion of the corticotropic adenoma after excision in one case of Cushing's disease. Before CRH injection in vivo results show significant central-peripheral gradients for all hormones but only ACTH lateralized to the side of the tumor. After CRH administration, the petrosal concentrations of all hormones increased preferentially on the side of the adenoma resulting in significant intersinus gradients: 8.1 for ACTH, 2.0 for GH, 1.8 for PRL and 1.5 for TSH. In vitro results: the adenoma cells were immunostainable for ACTH only. In culture, they secreted ACTH only. Addition of CRH to the culture induced a mean increase of 160% in ACTH secretion but GH, PRL and TSH remained undetectable. Our results favor the hypothesis that the multihormonal response to CRH seen during inferior petrosal sinus sampling in Cushing's disease reflects a paracrine stimulation of the adjacent non-tumorous pituitary cells by the corticotropic adenoma.
The relationship between first-phase insulin secretion and glucose metabolism
Authors: Widén Elisabeth IM , Eriksson Johan G , Ekstrand Agneta V , Groop Leif C
Published: June 2009

A possible pathogenetic link between absence of first-phase insulin secretion and development of impaired glucose metabolism has been suggested by the results of several cross-sectional studies. First-phase insulin secretion measured during a + 7 mmol/l hyperglycemic glucose clamp correlated with total glucose disposal during the clamp (r = 0.65, p <0.001, N = 59). To examine whether restoration of first-phase insulin secretion improves peripheral glucose uptake in subjects with impaired glucose utilization, seven insulin-resistant subjects (age 54 (38–62) years; BMI 29.3 (21.7–35.8); fasting plasma glucose 5.5 (4.8–7.2) mmol/l; fasting insulin 57 (37–105) pmol/l with impaired first-phase (148 (29–587) vs controls 485 (326–1086) pmol/l× 10 min; p<0.05) and normal second-phase (1604 (777–4480) vs controls (1799 (763–2771) pmol/l × 110 min) insulin secretion were restudied. The impaired first-phase insulin secretion was restored by an iv insulin bolus at the start of the hyperglycemic clamp. Substrate oxidation rates and hepatic glucose production were determined by indirect calorimetry and [3-3H]glucose infusion. Total glucose uptake was impaired in the insulinresistant subjects with impaired first-phase insulin secretion compared to controls (18.8 (13.2–22.2) vs 34.8 (24.3–62.1) μmol·kg−1·min−1; p<0.01). Restoration of first-phase insulin secretion (1467 (746–2440) pmol/l× 10 min) did not affect glucose uptake (20.2 (9.9–23.8) μmol·kg−1·min−1), with no difference in oxidative and non-oxidative glucose metabolism between the experiments. Second-phase insulin secretion was similar during both experiments. We conclude that although first-phase insulin secretion correlates with total glucose uptake, replacement of impaired first-phase insulin secretion does not improve glucose uptake in subjects with impaired glucose disposal and normal second-phase insulin secretion. The data dispute a causal relationship between first-phase insulin secretion and impaired glucose uptake in these subjects.
Plasma levels of insulin-like growth factor binding protein-1, and growth hormone binding protein activity from birth to the third month of life
Authors: Bernardini Sergio , Spadoni Gian Luigi , Pòvoa Guilhèrme , Boscherini Brunetto , Hall Kerstin
Published: June 2009

Serum levels of insulin-like growth factors (IGF-1 and IGF-2), insulin, insulin-like growth factor binding protein-1 (IGFBP-1), growth hormone (GH) and growth homone-binding protein (GH-BP) activity were assessed in a group of healthy newborns and reevaluated at one and three months of life in six of them. A significant decrease in IGFBP-1 plasma levels was observed at one month (p< 0.002) and three months (p< 0.02) of life compared to cord blood values. IGF-1 plasma levels did not change during the first three months of life. In contrast, IGF-2 plasma levels increased significantly at three months of life compared to cord blood values (p< 0.002). GH plasma levels showed a significant decrease at three months of life (p<0.03). GH-BP activity was low at birth and did not change significantly during the first three months of life. The low GH-BP activity may reflect the GH receptor status, indicating that GH receptors are poorly expressed in early infancy. The high IGFBP-1 plasma levels in newborns could be important in protecting them from hypoglycemia.
Serum levels of intact parathyroid hormone and alkaline phosphatase correlate with cortical and trabecular bone loss in primary hyperparathyroidism
Authors: Pfeilschifter Johannes , Siegrist Elisabeth , Wüster Christian , Blind Eberhard , Ziegler Reinhard
Published: June 2009

We examined the relationship between bone loss and several biochemical indices in 38 patients with primary hyperparathyroidism. Bone mineral density was reduced by 12±4.0% in the lumbar spine, 18±4.2% at the distal radius and 21±2.8% at the proximal radius (mean±sem). There were significant negative correlations between the serum concentrations of intact parathyroid hormone (PTH) and the Z-scores of the bone mineral content at the proximal and distal radius. In the lumbar spine, bone mineral density was greater in patients with mildly elevated PTH and less in patients whose PTH levels exceeded 8.6 pmol/l. We also observed a strong association between increased levels of serum alkaline phosphatase and low bone mineral Z-scores. Our data thus indicate that cortical and, with the exception of mild primary hyperparathyroidism, trabecular bone loss is proportional to the concentration of circulating PTH and the severity of PTH-induced bone turnover. For the individual patient, however, the usefulness of intact PTH and alkaline phosphatase measurements for assessing bone loss associated with primary hyperparathyroidism seems to be only limited.
Serum parathyroid hormone-related protein concentrations in patients with hematologic malignancies or solid tumors
Authors: Nakamura Yuriko , Bando Hiroshi , Shintani Yasumi , Yokogoshi Yutaka , Saito Shiro
Published: June 2009

The clinical significance of parathyroid hormone-related protein in humoral hypercalcemia of malignancy was investigated by determining the serum parathyroid hormone-related protein concentrations in 167 normal subjects, 56 patients with hematologic malignancy and 144 patients with solid tumor. Serum parathyroid hormone-related protein was measured with a radioimmunoassay kit that recognizes the C-terminal portion of the molecule. The serum parathyroid hormone-related protein concentrations were 20.2–50.8 pmol/l (mean±2 sd) in normal subjects, and were elevated in 80% of the patients with malignancies with hypercalcemia, including squamous cell carcinoma and adult T cell leukemia. Moreover, two cases of B cell non-Hodgkin's lymphoma with hypercalcemia had high serum parathyroid hormone-related protein concentrations, which varied in parallel with the tumor size during the clinical course. Of 136 patients with solid tumors with normocalcemia, the serum parathyroid hormone-related protein concentration was slightly elevated in only 5.1%, all of whom were at an advanced stage. These data indicate that determination of the serum parathyroid hormone-related protein concentration is useful for differential diagnosis of humoral hypercalcemia of malignancy and prediction of its development.
Effect of melatonin on the in vitro secretion of progesterone and estradiol 17β by ovine granulosa cells
Authors: Baratta Mario , Tamanini Carlo
Published: June 2009

This study was undertaken to determine the effect of melatonin on steroid hormone production by ovine granulosa and luteal cells in vitro. Granulosa and luteal cells from ovine ovaries were cultured for nine days either in D-MEM only or in the presence of melatonin (0.86, 8.6, 86 nmol/l), ovine luteinizing hormone (oLH, 2 μg/l) or a combination of both these hormones. Progesterone (P4) and estradiol 17β (E2) were determined by validated RIAs. Melatonin stimulation began at either day 1 or day 5 of culture. Melatonin (0.86 nmol/l) significantly increased (p<0.001) progesterone secretion by granulosa cells both when administered alone and when administered in combination with oLH; the more marked response was observed in the latter case. When the stimulation began at day 5, at a more advanced degree of differentiation of the cells, higher levels of P4 were observed. Higher concentrations of melatonin did not further increase progesterone production. Melatonin alone did not have a significant effect on the production of estradiol 17β; neither did melatonin stimulate progesterone production in either long-term cultured luteal cells or in short-term (1–2 h) cultured luteal and granulosa cells. The results of this study document a direct effect of melatonin in stimulating granulosa cells to produce progesterone, a synergistic activity between melatonin and luteinizing hormone and a different ability of granulosa cells to secrete P4 depending on the degree of differentiation.
Antigonadotropic activity of hop extract
Authors: Okamoto Ryohei , Kumai Akihiko
Published: June 2009

Biological activity of water soluble fractions F-1 and F-2, which were extracted from hop, was studied and its action mechanism was speculated using the immature female sd rats. Administration of the substance significantly inhibited the effects of pregnant mare serum gonadotropin (PMSG) on 22-day-old female rats. Thus, PMSG-induced increases in ovarian weight, estrogen secretion, number of ovulated egg, progesterone production, uterine thymidine kinase activity, and plasma LH level were suppressed significantly. Furthermore, addition of the substance to incubated ovarian cells of the second day after PMSG injection resulted in suppression of FSH-induced estradiol secretion in vitro, probably via cAMP-dependent mechanism. But addition of the substance to incubated pituitary cells from ovariectomized rats did not change in LH secretion.
Somatostatin inhibits the norepinephrine-activated calcium channels in rMTC 6–23 cells: possible involvement of a pertussis toxin-sensitive G-protein
Authors: Zink A , Raue F
Published: June 2009

The mechanisms by which somatostatin inhibits hormone release are complex and involve, among other things, reduction of both intracellular cAMP and intracellular calcium. We studied the influence of the long-acting somatostatin analogue octreotide on norepinephrine (NE)-induced changes in intracellular calcium ([Ca2+]i) in fura-2 loaded single cells of a rat medullary carcinoma cell line, rMTC 6–23. Increases in the extracellular calcium concentration ([Ca2+]e) induced a sudden rise in [Ca2+]i which could be blocked by EGTA or the calcium channel blocker verapamil. NE evoked a similar increase in [Ca2+]i, which also could be blocked by the addition of EGTA or verapamil. Octreotide prevented or reversed the NE-induced increase in [Ca2+ ]i. Pretreatment of the cells with pertussis toxin abolished the inhibitory effect of octreotide. Thus we conclude that the NE-induced rise in [Ca2+]i is due to an influx of [Ca2+ ]e, most probably through voltage-dependent calcium channels. Octreotide inhibits the NE-stimulated rise in [Ca2+ ]i by a pertussis toxin-sensitive G-protein, most probably through a direct effect on NE-activated calcium channels.