bluuebunny/crossref_metadata_2025_split huggingface dataset:
Possible role of corticosterone in the down-regulation of the hypothalamo-hypophysial-thyroid axis in streptozotocin-induced diabetes mellitus in rats
Authors: van Haasteren G A C , Sleddens-Linkels E , van Toor H , Klootwijk W , de Jong F H , Visser T J , de Greef W J 
Published: December 2004

Abstract
We investigated the effects of diabetes mellitus on the hypothalamo-hypophysial-thyroid axis in male (R×U) F1 and R-Amsterdam rats, which were found to respond to streptozotocin (STZ)-induced diabetes mellitus with no or marked increases, respectively, in plasma corticosterone. Males received STZ (65 mg/kg i.v.) or vehicle, and were killed 1, 2 or 3 weeks later. At all times studied, STZ-induced diabetes mellitus resulted in reduced plasma TSH, thyroxine (T4) and 3,5,3′-tri-iodothyronine (T3). Since the dialyzable T4 fraction increased after STZ, probably as a result of decreased T4-binding prealbumin, plasma free T4 was not altered during diabetes. In contrast, both free T3 and its dialyzable fraction decreased during diabetes, which was associated with an increase in T4-binding globulin. Hepatic activity of type I deiodinase decreased and T4 UDP-glucuronyltransferase increased after STZ treatment. Thus, the lowered plasma T3 during diabetes may be due to decreased hepatic T4 to T3 conversion.
Median eminence content of TRH increased after STZ, suggesting that hypothalamic TRH release is reduced during diabetes and that this is not caused by impaired synthesis or axonal transport of TRH to the median eminence. Hypothalamic proTRH mRNA did not change in diabetic (R×U) F1 rats during the period of observation, but was lower in R-Amsterdam rats 3 weeks after STZ. Similarly, pituitary TSH and TSHβ mRNA had decreased in R-Amsterdam rats by 1 week after STZ treatment, but did not change in (R×U) F1 rats. The difference between the responses in diabetic R-Amsterdam and (R×U) F1 rats may be explained on the basis of plasma corticosterone levels which increased in R-Amsterdam rats only. Hypothalamic TRH content was not affected by diabetes mellitus, but the hypothalami of diabetic rats released less TRH in vitro than those of control rats. Moreover, insulin had a positive effect on TRH release in vitro.
In conclusion, the reduced hypothalamic TRH release during diabetes is probably not caused by decreases in TRH synthesis or transport to the median eminence, but seems to be due to impaired TRH release from the median eminence which may be related to the lack of insulin. Inhibition of proTRH and TSHβ gene expression in diabetic R-Amsterdam rats is not a primary event but appears to be secondary to enhanced adrenal activity in these animals during diabetes.
Journal of Endocrinology (1997) 153, 259–267
Concentration of free growth hormone-binding protein in the serum of mice is not regulated by growth hormone
Authors: Sotelo A I , Dominici F P , Bartke A , Turyn D 
Published: December 2004

Abstract
Ames dwarf mice that do not express growth hormone (GH) or prolactin (PRL) genes were used to study the effects of GH deficiency on the presence and the characteristics of GH-binding protein (GHBP) in serum. Chromatographic techniques were used to allow characterization of biological rather than immunological activity of GHBP. Two GH-binding fractions were found in dwarf mice serum, one with low affinity and high capacity (GHBPI) and one with high affinity, low capacity and lower molecular mass (GHBPII). Serum concentration of the high-affinity GHBP was 0·73 ± 0·03 nm with a Kd of 6·3 ± 1·7 nm. Since Ames dwarf mice have no GH in the circulation, all the GHBP is free. Interestingly, the concentration of GHBP in dwarf mice was similar to the levels of free GHBP measured in normal mice from the same line. Moreover, this value (0·7 nm) closely resembles the concentration of free GHBP in the serum of transgenic mice overexpressing GH, in which peripheral GH levels are grossly elevated. These observations can be interpreted as evidence that the levels of free GHBP in mouse serum are independent of GH concentration, and that GH influences only the levels of bound GHBP in peripheral circulation.
Journal of Endocrinology (1997) 153, 319–325
Administration of IGF-I affects the GH axis and adolescent growth in normal monkeys
Authors: Wilson M E 
Published: December 2004

Abstract
The present study examined the effects of IGF-I on serum concentrations of IGF binding protein-3 (IGFBP-3) and GH and assessed how treatment with estradiol and IGF-I would stimulate adolescent growth in monkeys with normal pituitary function. In study I, ovariectomized, juvenile female rhesus monkeys (21 months of age; n=6) received a bolus injection of IGF-I (1 mg/kg s.c.) and serum samples were collected periodically through 48 h. The consequential elevation in serum IGF-I resulted in a parallel increase in serum IGFBP-3 at 1 and 3 h after treatment with values returning to baseline by 7 h. In contrast, the elevation in serum IGF-I resulted in a significant decline in serum GH within 3 h of treatment. These data confirm that an elevation in IGF-I increases IGFBP-3 while simultaneously acting in a negative feedback capacity to inhibit GH.
In study II, ovariectomized, juvenile female rhesus monkeys served either as controls (Con, n=6) or received a constant s.c. infusion of IGF-I (300 μg/day; Igf, n=6) from 13 through 32 months of age. At approximately 26 months, females entered an estradiol-treatment protocol in which they received alternating blocks of 3 weeks of estradiol followed by 3 weeks of no estradiol. As found in study I, the elevation in serum IGF-I resulted in a significant increase in serum IGFBP-3 throughout the study in Igf compared with Con females. Estradiol administration significantly increased serum IGF-I and IGFBP-3 levels in both groups. Although the nano-molar ratio of IGF-I to IGFBP-3 was consistently higher in Igf females, the magnitude of the change in IGF-I:IGFBP-3 following estradiol treatment was similar between groups. Finally, the age-dependent increase in serum GH was dampened in Igf compared with Con females and the increase in response to estradiol was less in Igf females. Although total growth in crown-rump length was similar in both groups, Igf females grew more prior to estradiol replacement while Con females grew more once estradiol treatment was initiated. In addition, skeletal maturity was advanced more quickly in Igf females once estradiol treatment had been initiated.
These data suggest that, in female monkeys with normal pituitary function, IGF-I administration inhibits endogenous GH secretion but is capable of stimulating crownrump growth. Although IGF-I increased serum levels of IGFBP-3, the increase was not proportional to the increase in serum IGF-I achieved by the treatment. These data would suggest that IGF-I may regulate the release of this binding protein but that GH may be required to maintain equi-molar proportions of IGF-I to IGFBP-3. In addition, the observation that serum concentrations of IGF-I were increased further in IGF-I-treated females by the administration of estradiol without a change in serum GH, suggests that estradiol has a direct effect on IGF-I synthesis and release independent of GH.
Journal of Endocrinology (1997) 153, 327–335
Prolactin receptors in human meningiomas: characterization and biological role
Authors: Muccioli G , Ghè C , Faccani G , Lanotte M , Forni M , Ciccarelli E 
Published: December 2004

Abstract
Sixty cerebral meningioma specimens obtained at surgery from 34 female and 26 male patients were examined for the presence of prolactin (PRL) receptors. These were compared with normal arachnoid tissue from which these tumours arise. PRL receptors were detected in 61·7% of meningiomas whereas no PRL binding was found in samples of normal arachnoid tissue. No relationship was found when sex or histological findings were compared with the presence of PRL receptors. Receptor-positive tumours had saturable and high-affinity (Kd, 4·8 ± 0·5 ng/ml) receptors with hormonal specificity for human PRL (hPRL) resembling that of other target tissues of PRL in man. The biological role of these receptors was investigated in primary cell cultures derived from meningioma tissue characterized for PRL receptor. When human PRL was added to the culture medium, in doses ranging from 1 to 200 ng/ml, a dose-dependent stimulation of 3H-thymidine incorporation was observed only in PRL-receptor positive tumours. The PRL concentrations required to produce a half-maximal effect ranged from 11 to 20 ng/ml and were quite close to the dissociation constant (Kd) of binding of PRL to its receptors. PRL also caused an increase of cell number compared with control with a significant effect after 3 and 4 days of culture.
In conclusion, these findings indicate that a large number of human meningiomas express specific and functional receptors for PRL which are involved in mediating its proliferative effects.
Journal of Endocrinology (1997) 153, 365–371
Effect of insulin-induced hypoglycaemia on secretion patterns and rates of corticotrophin-releasing hormone, arginine vasopressin and adrenocorticotrophin in horses
Authors: Alexander S L , Roud H K , Irvine C H G 
Published: December 2004

Abstract
To study the effect of hypoglycaemia on secretion rates of corticotrophin-releasing hormone (CRH), arginine vasopressin (AVP) and ACTH in a non-ruminant species, a non-surgical method was used to collect pituitary venous (PitVen) blood every 0·5 or 1 min from seven horses before and after insulin administration (0·4 U/kg i.v.). To assess the effect of PitVen cannulation on results, peripheral hormones were also measured before and after insulin in five horses without PitVen cannulae.
Insulin administration lowered plasma glucose in all horses (P<0·0001; paired t-test). Cortisol concentrations, which were similar in horses with and without PitVen cannulae before insulin, rose significantly after insulin administration in both groups. Most horses showed discomfort as glucose fell. When data from horses with and without PitVen cannulae were pooled, the peak fractional change in cortisol (Spearman's rank correlation coefficient (rs)= −0·94, P<0·001) and the severity of hypoglycaemic symptoms (rs= −0·61, P<0·02) were inversely ranked with the glucose nadir. In horses with PitVen cannulae, insulin administration increased secretion rates of ACTH (P<0·0001), AVP (P<0·0001) and CRH (P<0·02). Increments in ACTH (rs=−0·96, P<0·005) and CRH (rs= −0·81, P<0·05), but not in AVP, measured during the second half-hour after insulin (i.e. the peak response), were inversely ranked with the glucose nadir. Moreover, ACTH increments were positively ranked with those in CRH (rs=0·81, P<0·05), but not in AVP. Nevertheless, in individual horses, minute-to-minute AVP and ACTH concentrations in PitVen blood were always correlated, whereas minute-to-minute CRH and ACTH concentrations were correlated only when glucose dropped below 3·4 mmol/l. In less hypoglycaemic horses, ACTH secretion rose despite little or no change in CRH.
We suggest that in horses AVP is the primary acute signal for ACTH release both before and during hypoglycaemia; however, the increasing magnitude of ACTH increments induced by greater degrees of hypoglycaemia is determined largely by selective CRH release, which then augments corticotroph responses to AVP.
Journal of Endocrinology (1997) 153, 401–409
Ca2+ receptor mRNA and protein increase in the rat parathyroid gland with advancing age
Authors: Autry C P , Kifor O , Brown E M , Fuller F H , Rogers K V , Halloran B P 
Published: December 2004

Abstract
Parathyroid hormone (PTH) release is regulated by extracellular calcium through a Ca2+ receptor (CaR) located on the surface of the parathyroid cell. With advancing age, the serum concentration of PTH increases, and evidence suggests that the calcium set-point for PTH release may also increase. To determine whether these changes are linked to a change in CaR expression, we quantitated mRNA and protein for the receptor in parathyroid glands of 6-week-, 6-month- and 24-month-old rats. Thyroid and kidney tissue were also studied. Between 6 weeks and 24 months of age, CaR mRNA in the parathyroid gland increased 11·4- and 3·3-fold as measured by competitive reverse transcription PCR and solution hybridization assays respectively. Message levels for the receptor also increased in the thyroid but not in the kidney. Coincident with the increase in message levels, receptor protein concentration in the parathyroid increased 7-fold between 6 weeks and 24 months of age. These results suggest that the altered relationship between extracellular calcium and PTH release observed in aging is associated with dramatic changes in CaR metabolism. That PTH secretion is increased despite increased receptor concentration suggests that aging may impair calcium binding or coupling between the CaR and down-stream effector elements in the pathway regulating PTH release.
Journal of Endocrinology (1997) 153, 437–444
Measurement of N- and C-terminal-region fragments of parathyroid hormone-related peptide in milk from lactating women and investigation of the relationship of their concentrations to calcium in milk
Authors: Uemura H , Yasui T , Yoneda N , Irahara M , Aono T 
Published: December 2004

Abstract
Parathyroid hormone-related peptide (PTHrP) is found in very high concentrations in the milk of various mammals. However, little is known about its physiological role in this fluid. To obtain detailed profiles of PTHrP in milk, we measured the concentrations of PTHrP in human milk by two different region-specific assays, PTHrP(1–87) (N-PTHrP) and PTHrP(109–141) (C-PTHrP). We also examined the correlations between PTHrP and Ca concentrations in milk as well as the correlations between PTHrP and secreted milk volume.
The levels of N-PTHrP and C-PTHrP were relatively low after delivery and gradually increased to 13·87 ± 2·40 nmol/l (mean ± s.e.m.) and 56·39 ± 11·31 nmol/l respectively on the 10th day postpartum. N-PTHrP concentration remained steady until the 6th month postpartum when weaning starts, at which point it decreased slightly. C-PTHrP levels changed in a similar way to N-PTHrP levels but were 2- to 5-fold higher. Milk Ca concentration, and content, correlated with C-PTHrP concentration, and content (r=0·422 and r=0·769 respectively; P<0·0001) but not with N-PTHrP. N-PTHrP concentration in the milk samples on the 4th day postpartum correlated with the volume of milk secreted during the 24 h before the samples were taken (r=0·524, P<0·01), but C-PTHrP concentration did not.
These results suggest that PTHrP in human milk may play some role in the maintenance of lactation through the N-terminal region and in promoting Ca transfer into milk via the C-terminal region.
Journal of Endocrinology (1997) 153, 445–451
Intracellular regulation of 17β-hydroxysteroid dehydrogenase type 2 catalytic activity in A431 cells
Authors: Blomquist C H , Leung B S , Beaudoin C , Poirier D , Tremblay Y 
Published: December 2004

Abstract
There is growing evidence that various isoforms of 17β-hydroxysteroid dehydrogenase (17-HSD) are regulated at the level of catalysis in intact cells. A number of investigators have proposed that the NAD(P)/NAD(P)H ratio may control the direction of reaction. In a previous study, we obtained evidence that A431 cells, derived from an epidermoid carcinoma of the vulva, are enriched in 17-HSD type 2, a membrane-bound isoform reactive with C18 and C19 17β-hydroxysteroids and 17-ketosteroids. The present investigation was undertaken to confirm the presence of 17-HSD type 2 in A431 cells and to assess intracellular regulation of 17-HSD at the level of catalysis by comparing the activity of homogenates and microsomes with that of cell monolayers. Northern blot analysis confirmed the presence of 17-HSD type 2 mRNA. Exposure of cells to epidermal growth factor resulted in an increase in type 2 mRNA and, for microsomes, increases in maximum velocity (Vmax) with no change in Michaelis constant (Km) for testosterone and androstenedione, resulting in equivalent increases in the Vmax/Km ratio consistent with the presence of a single enzyme. Initial velocity data and inhibition patterns were consistent with a highly ordered reaction sequence in vitro in which testosterone and androstenedione bind only to either an enzyme–NAD or an enzyme–NADH complex respectively. Microsomal dehydrogenase activity with testosterone was 2- to 3-fold higher than reductase activity with androstenedione. In contrast, although cell monolayers rapidly converted testosterone to androstenedione, reductase activity with androstenedione or dehydroepiandrosterone (DHEA) was barely detectable. Lactate but not glucose, pyruvate or isocitrate stimulated the conversion of androstenedione to testosterone by monolayers, suggesting that cytoplasmic NADH may be the cofactor for 17-HSD type 2 reductase activity with androstenedione. However, exposure to lactate did not result in a significant change in the NAD/NADH ratio of cell monolayers. It appears that within A431 cells 17-HSD type 2 is regulated at the level of catalysis to function almost exclusively as a dehydrogenase. These findings give further support to the concept that 17-HSD type 2 functions in vivo principally as a dehydrogenase and that its role as a reductase in testosterone formation by either the Δ4 or Δ5 pathway is limited.
Journal of Endocrinology (1997) 153, 453–464
Modulation of human neutrophil function in vitro by gastrin
Authors: De la Fuente M , Carrasco M , Hernanz A 
Published: December 2004

Abstract
We have studied the effects in vitro of gastrin-17 and gastrin-34, at concentrations from 10−14 m to 10−6 m, on several of the functions of peripheral blood human neutrophils, i.e. adherence to substrate, mobility (spontaneous and directed by a chemical gradient or chemotaxis), ingestion of inert particles (latex beads) and cells (Candida albicans) and superoxide anion production. Both gastrins inhibited several steps of the phagocytic process of human neutrophils, such as mobility and ingestion. By contrast, these peptides increased adherence and had no effect on superoxide anion production. In general, these effects were significant at peptide concentrations between 10−12 m and 10−8 m with a maximal effect at 10−10 m. In addition, gastrin peptides induced a significant increase in intracellular cAMP levels at 30, 60 and 120 s. Moreover, the inhibitory effect of gastrin-17 on the ingestion capacity of neutrophils (latex bead phagocytosis) was similar to that obtained with EGTA, a well-known extracellular calcium chelating compound. Gastrin-17 was found to inhibit completely the stimulation of latex bead phagocytosis in neutrophils caused by the calcium ionophore A23187. These results suggest that gastrin is a negative modulator of the phagocytic process of human neutrophils, and that this effect might involve an increase in intracellular cAMP levels and a decrease in calcium entry into the cells.
Journal of Endocrinology (1997) 153, 475–483
Immunolocalisation of oestrogen receptor-α within the testis and excurrent ducts of the rat and marmoset monkey from perinatal life to adulthood
Authors: Fisher J S , Millar M R , Majdic G , Saunders P T K , Fraser H M , Sharpe R M 
Published: December 2004

Abstract
The sites of action and the physiological role of oestrogens in the male reproductive tract are poorly understood. We have undertaken a systematic study of the immunoexpression of oestrogen receptor-α (ERα) in the male rat from late fetal life through to adulthood and compared the findings with results obtained in the marmoset monkey (Callithrix jacchus) from neonatal to adult life. The testes, rete testis, efferent ducts and epididymis were examined from normal male rats (aged 4, 8, 10, 15, 20, 25, 38, 48 and 90 days) and from male rat fetuses on days 17·5 and 18·5 of gestation; comparable tissues were examined from neonatal, infantile, peripubertal and adult marmosets aged 8, 18–24, 54–62 and 92–112 weeks respectively. Immunolocalisation of ERa used antigen retrieval and a monoclonal antibody directed to the N-terminus, which had proved superior to six other antisera tested. ERa was immunoexpressed in interstitial cells, including the fetal/neonatal generation of Leydig cells, in both the rat and marmoset. In the rat, the adult generation of Leydig cells were also immunopositive for ERa whereas the comparable cells in the marmoset were only weakly immunopositive. ERa was not expressed in Sertoli cells, peritubular myoid cells, blood vessels or germ cells at any time in either species. In late fetal life in the rat, ERa was immunoexpressed in cells surrounding the mesonephric tubules, whereas postnatally it was expressed in the epithelium of the rete testis and efferent ducts at all ages from 4 to 90 days; this immunoexpression was most pronounced in the efferent ducts. In the marmoset, the efferent ducts, but not the rete testis, also showed intense immunoexpression of ERa. Apart from sporadic immunostaining for ERa in the epididymal duct of the rat in the neonatal period, the caput, corpus and cauda epididymis were negative for immunoexpression of ERa at all ages in both species. These findings suggest that the main actions of oestrogens in the male reproductive tract, mediated by ERa, are related to the development and function of the efferent ducts and the Leydig cells. In consideration of data from this and previous studies of oestrogen binding, we predict possible sites of expression of other oestrogen receptors (e.g. ERβ) in Sertoli cells and the epididymis. Interactive effects, related to the relative levels of androgens and oestrogens, could be physiologically important in the excurrent ducts of the adult testis.
Journal of Endocrinology (1997) 153, 485–495
The desensitization of oxytocin receptors in human myometrial cells is accompanied by down-regulation of oxytocin receptor messenger RNA
Authors: Phaneuf S , Asbóth G , Carrasco M P , Europe-Finner G N , Saji F , Kimura T , Harris A , Bernal A López 
Published: December 2004

Abstract
We have recently provided evidence for the desensitization of oxytocin receptors in human myometrial cells. In the present study, we have investigated the possible mechanisms by which oxytocin (OT) might regulate OT receptor density. The steady state level of OT binding in cultured myometrial cells was 220 × 103 binding sites/cell, but this was time-dependently reduced to 27 × 103 sites/cell by exposure to OT for up to 20 h. Similarly, OT exposure decreased the binding of OT to cell membranes. In contrast, Western blotting data showed that the total amount of OT receptor protein was not affected by OT treatment for up to 48 h. Flow cytometry experiments demonstrated that OT receptors are not internalized during prolonged exposure of the cells to OT. However, RNase protection assays and Northern analysis showed that OT receptor mRNA was reduced by OT treatment to reach a new low steady state level with a time course similar to that of the disappearance of cell surface OT binding sites. Possible mechanisms involved in mRNA down-regulation include transcriptional suppression and destabilization of mRNA by RNA binding proteins.
Journal of Endocrinology (1997) 154, 7–18