bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of components of the insulin-like growth factor system in pig mammary glands and serum during pregnancy and pseudopregnancy: effects of oestrogen
Authors: Lee C. Y. , Bazer F. W. , Simmen F. A. 
Published: December 2008

ABSTRACT
To gain insight into the involvement and interactions of the insulin-like growth factors (IGFs) and oestrogen in mammary growth and differentiation, the temporal expression of mammary mRNAs encoding components of the IGF system in pregnant and pseudopregnant pigs was examined. Pseudopregnant pigs received 5 mg oestradiol valerate or vehicle daily from day 45 after oestrus and underwent mammary biopsy on days 60, 90 or 112. In mammary tissue of pregnant pigs, steady-state levels of the mRNAs encoding IGF-I, IGF-II and type-I IGF receptor as well as the levels of the membrane-associated type-II IGF receptor were higher during the early phase of mammogenesis (≤day 45) than during the subsequent stages of mammary development. Mammary IGF-I, IGF-II and type-I receptor mRNAs were expressed at their lowest levels around day 90 of pregnancy (20–40% of those for day 30 of pregnancy) coincident with the onset of β-casein mRNA accumulation. Mammary IGF-binding protein-2 (IGFBP-2) mRNA levels increased twofold during the latter half of pregnancy, whereas the amount of IGFBP-3 mRNA declined after day 30 to undetectable levels by midpregnancy. Pseudopregnant pigs had reduced levels of these mRNAs (except for IGF-II) relative to their pregnant counterparts and this was associated with premature differentiation of mammary tissue as reflected by an earlier onset of β-casein mRNA accumulation in the former. The administration of oestradiol valerate decreased the levels of IGF-I and type-I IGF receptor mRNAs by day 60 of pseudopregnancy, but the reverse was evident by day 112. Oestradiol administration increased β-casein mRNA levels in pseudopregnant pigs, but had no effect on mammary IGFBP-2 and IGFBP-3 mRNA levels. Mammary IGF content was greater in late pregnancy (≥day 90) and pseudopregnancy than at early pregnancy. Serum IGF-I and IGF-II levels declined steadily during pregnancy and this was similar to, but not correlated with, mammary IGF mRNA levels, whereas in pseudopregnant pigs, serum IGF concentrations did not change temporally or in response to oestradiol. Serum IGFBP-2 levels were unaltered during pregnancy or pseudopregnancy, but serum IGFBP-3 levels declined after day 60 of pregnancy. In pseudopregnant pigs, serum IGFBP-3 levels did not change temporally, but declined after oestradiol treatment. Results indicate that mammary IGF-I and type-I IGF receptor systems are down-regulated during pregnancy-associated differentiation of this tissue and in response to oestrogen. Locally produced (autocrine and paracrine) IGFs are likely to mediate mammogenesis, whereas oestrogen stimulates mammary differentiation and lactogenesis in the pig. However, the high mammary IGF content and the reciprocal expression of mammary IGFBP-2 and IGFBP-3 mRNAs during late pregnancy suggests the involvement of IGFs in lactogenesis as well.
Journal of Endocrinology (1993) 137, 473–483
Relaxin alters the plasma osmolality-arginine vasopressin relationship in the rat
Authors: Weisinger R. S. , Burns P. , Eddie L. W. , Wintour E. M. 
Published: December 2008

ABSTRACT
During pregnancy, in women and the rat, there is a resetting of the plasma osmolality–arginine vasopressin relationship (Posmol/PAVP) such that a decrease in Posmol is maintained without suppression of PAVP. This occurs at a time when relaxin is detectable in plasma. The hypothesis tested here was that relaxin could alter the Posmol/PAVP in the non-pregnant rat. One group of ovariectomized rats (n = 15) was treated for 7 days with intravenous synthetic human relaxin (10 μg/h) in 10 pi 0·9% (w/v) NaCl. Controls were two groups of rats either with no treatment (n = 15) or treated with vehicle alone (n = 15). One-third of each group received hypertonic saline (0·4 mol NaCl/l, 2 ml/100 g body weight i.p.) on day 7, and one-third were deprived of water for the final 24 h. All rats were killed by decapitation and blood was collected rapidly (<40 s) for hormone and osmolality assays. The Posmol in all relaxin-treated rats was significantly (P < 0·001) lower than that in both control groups, but the PAVP was unchanged. The log PAVP/Posmol regression line was significantly shifted in elevation (P <0·001) but not in slope. Thus treatment of ovariectomized rats with relaxin caused changes in fluid balance which mimic those occurring in normal pregnancy.
Journal of Endocrinology (1993) 137, 505–510
Modulation of the prostaglandin responses of conscious rabbits to the pyrogen polyinosinic: polycytidylic acid by corticotrophin-releasing factor-41
Authors: Milton N. G. N. , Hillhouse E. W. , Milton A. S. 
Published: December 2008

ABSTRACT
The pyrogenic interferon inducer polyinosinic: polycytidylic acid (Poly I: C) was shown to stimulate rises in both prostaglandin E2 (PGE2) and prostaglandin F2α (PGF2α) in conscious rabbits in vivo. Poly I:C (2·5 μg/kg) stimulated a fivefold rise in circulating immunoreactive (ir) PGE2, with a lag phase of 60 min, which was sustained during the subsequent 4-h period of observation. Poly I:C also stimulated a 2·5-fold rise in circulating irPGF2α with a lag phase of 90 min, which was followed by a return to basal levels after 5 h. The rises in circulating irPGE2 and irPGF2α stimulated by Poly I:C were prevented by pretreatment with the non-steroidal anti-inflammatory drug ketoprofen. Both the irPGE2 and irPGF2α responses to Poly I:C (2·5 μg/kg, i.v.) were antagonized by the corticotrophin-releasing factor-41 (CRF-41) receptor antagonist (α-helical CRF (9–41), 25 μg/kg, i.v.) administered 5 min prior to the pyrogen. Peripheral immunoneutralization using an anti-CRF-41 monoclonal antibody (KCHMB001, 2·5 mg/kg, i.v.) administered 5 min prior to the pyrogen, also inhibited both the PGE2 and PGF2α responses to Poly I:C (2·5 μg/kg, i.v.). However, control mouse IgG also inhibited the PGE2 response. In conclusion, these results suggest a modulatory role for endogenous peripheral CRF-41 in the circulating prostaglandin responses to the pyrogen Poly I: C and this effect may be responsible for the antipyretic actions of peripherally administered CRF-41 antagonists and antibodies.
Journal of Endocrinology (1993) 138, 7–11
[125I]Iodomelatonin-binding sites in the bursa of Fabricius of birds: binding characteristics, subcellular distribution, diurnal variations and age studies
Authors: Liu Z. M. , Pang S. F. 
Published: December 2008

ABSTRACT
The melatonin-binding sites in membrane preparations of the bursa of Fabricius of birds were studied using [125I]iodomelatonin as a radioligand. The binding sites were stable, saturable, reversible and of high affinity. Scatchard analysis of specific binding revealed equilibrium binding constants (Kd) of (means±s.e.m.) 43·1 ±5·9 73·3±7·6 and 35·3±4·8 pmol/l respectively at the mid-point of the light period (mid-light) in chickens, pigeons and quail, with a total number of binding sites (Bmax) of 1·23 ±0·15, 1·33±0·18 and 0·94 ±0·07 fmol/mg protein. The diurnal variation in [125I]iodomelatonin binding showed that the Bmax was 45, 115 and 70% higher at mid-light than at mid-dark in the bursae of chickens, pigeons and quail respectively. The Kd value determined from kinetic analysis was 49·0 ±6·4 pmol/l at mid-light in the chicken bursa. The [125I]iodomelatonin-binding sites of chicken bursal membranes had the following order of pharmacological affinities: 2-iodomelatonin > melatonin > 6-chloromelatonin > 6-hydroxymelatonin > N-acetylserotonin > 5-hydroxytryptamine, tryptamine, 5-methoxytryptophol, 1-acetylindole-3-carboxaldehyde, 3-acetylindole, l-tryptophan, 5-hydroxyindole3-acetic acid, 5-hydroxytryptophan suggesting that the [125I]iodomelatonin-binding sites were highly specific for melatonin. The subcellular distribution of binding sites in the chicken bursa was in the following descending order: nuclear > mitochondrial > microsomal > cytosolic fraction. There was an agerelated decrease in [125I]iodomelatonin-binding in chicken bursal membranes, with higher densities in the neonate. Our studies of [125I]iodomelatonin-binding sites in the bird bursa indicate that this primary lymphoid tissue is a target organ for melatonin, and that melatonin has a direct effect on the immune system.
Journal of Endocrinology (1993) 138, 51–57
Vitamin D hydroxylases and their regulation in a naturally vitamin D-deficient subterranean mammal, the naked mole rat (Heterocephalus glaber)
Authors: Buffenstein R. , Sergeev I. N. , Pettifor J. M. 
Published: December 2008

ABSTRACT
The vitamin D hormone 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) is generated by a series of hydroxylation steps in the liver and kidneys. We investigated whether naturally vitamin D-deficient subterranean mammals (naked mole rats, Heterocephalus glaber) employ the same enzymatic pathways, and whether these are regulated in a similar manner to that established for other mammals.
Vitamin D3-25-hydroxylase in the liver and both 25-hydroxyvitamin D3-l-hydroxylase and 25-hydroxyvitamin D3-24 hydroxylase (1-OHase and 24-OHase) in the kidney were detectable in mole rats. As expected for vitamin D-deficient mammals, the 1-OHase activity predominated over the 24-OHase. After mole rats received a supraphysiological supplement of vitamin D3, 1-OHase activity was suppressed and 24-OHase activity was enhanced. Irrespective of vitamin D status, forskolin (a protein kinase A activator) and dibutyryl cyclic AMP did not alter the activity of either 1-OHase or 24-OHase. These findings suggest that the response of renal hydroxylases to parathyroid hormone was blunted. Phorbol esters, 12-O-tetradecanoylphorbol 13-acetate (TPA) and 1-oleoyl-2-acetylglycerol (OAG) (protein kinase C activators), suppressed 1-OHase activity. 24-OHase activity was induced by TPA but not by OAG. These effects were similar to those illicited by vitamin D3 supplementation but were additive in that they increased the responses shown in vitamin D-replete mole rats.
These data confirm that naturally vitamin D-deficient mole rats can convert vitamin D3 to the hormone, 1,25(OH)2D3. Furthermore, the enzymes 1-OHase and 24-OHase present in the kidneys of these mammals are regulated independently by 1,25(OH)2D3 and protein kinase C-mediated pathways of intracellular signalling, but are not regulated by the cyclic AMP–protein kinase A signal transduction pathway.
Journal of Endocrinology (1993) 138, 59–64
Phospholipid methylation decreases in human chorionic gonadotrophin-induced desensitized rat Leydig cells
Authors: Ronco A. M. , Valladares L. E. 
Published: December 2008

ABSTRACT
Phospholipid methylation in Leydig cells from desensitized rats was studied. The incorporation of l-[methyl-3H] methionine into phospholipids in intact Leydig cells decreased when animals were injected with a single high dose of human chorionic gonadotrophin (hCG). This effect was detected on the first day after hCG injection and remained up to 12 days after treatment. The inhibition was not due to a reduced uptake of l-[methyl-3H]methionine. A decreased phospholipid methylation with unaltered phospholipid methyltransferase activity was observed on days 1, 6 and 12 after the hCG. On day 3 after hCG injection, phospholipid methyltransferase activity and phospholipid methylation in intact Leydig cells were both inhibited by 40%. Also, a minimal amount of LH free receptors and the lowest number of total receptors was observed at this time. Thus, a relationship between the reduced enzymatic activity and the maximal decrease in LH surface receptors is suggested. In addition, the decreased incorporation of l-[methyl-3H]methionine into phospholipids on days 1, 6 and 12 after hCG injection, could be associated with other cellular changes related to the desensitization process.
Journal of Endocrinology (1993) 138, 65–71
Time-course of vertebral and femoral bone loss in rats administered gonadotrophin-releasing hormone agonist
Authors: Kurabayashi T. , Fujimaki T. , Yasuda M. , Yamamoto Y. , Tanaka K. 
Published: December 2008

ABSTRACT
This study was carried out (1) to compare the time-course of the change in bone metabolism in rats administered gonadotrophin-releasing hormone agonist (GnRHa) and bilaterally ovariectomized (OVX) rats and (2) to investigate the changes in bone metabolism after discontinuance of GnRHa.
Seventy female Sprague–Dawley rats, aged 90 days, were divided into four groups. Group 1 underwent a sham operation, group 2 was surgically ovariectomized and group 3 was given a GnRHa (leuprorelin acetate for depot suspension) s.c. injection every 30 days. Group 3 was further divided into three subgroups: rats were administered GnRHa for 12 months (GnRHa 12M), 6 months (GnRHa 6M) or 3 months (GnRHa 3M). Group 4 served as a basal control. The bone mineral density (BMD) of lumbar vertebrae and femoral bone, measured by dual-energy X-ray absorptiometry, and the serum bone metabolic parameters were determined every 45–90 days. The bone histomorphometry of lumbar vertebra was measured on days 180 and 360 after surgery.
GnRHa 12M rats showed significantly lower BMD of vertebrae and femoral bone, lower bone volume and higher bone turnover compared with sham-operated rats and those with secondary hyperparathyroidism on days 180 and 360. Their time-course for changes in bone metabolism was almost the same as that of OVX rats. GnRHa-discontinued rats showed a recovery of bone turnover. The recovery of BMD in GnRHa 6M rats was smaller than that of GnRHa 3M rats after GnRHa discontinuance. The bone volume for GnRHa 6M rats was significantly lower than that for GnRHa 3M on day 360.
Journal of Endocrinology (1993) 138, 115–125
Influence of endogenous cholinergic tone and α-adrenergic pathways on growth hormone responses to His-d-Trp-Ala-Trp-d-Phe-Lys-NH2 in the dog
Authors: Muruais J. , Peñalva A. , Dieguez C. , Casanueva F. F. 
Published: December 2008

ABSTRACT
His-d-Trp-Ala-Trp-d-Phe-Lys-NH2 (GHRP-6) is a synthetic peptide unrelated to any known hypothalamic-releasing hormone including growth hormone-releasing hormone (GHRH). Interestingly, this peptide induces a dose-related increase in plasma GH levels in all species tested so far. The aim of this study was to investigate the action of GHRP-6 alone or in combination with GHRH on GH release in dogs. In addition, the activation or blockade of endogenous cholinergic tone and α-1 adrenoceptors on GHRP-6-stimulated GH secretion was assessed.
In adult Beagle dogs (n = 10), GHRP-6 (90 μg i.v.) increased basal GH levels from 2·6 ± 1·5 to 14·4 ± 3·1 μg/l (mean ± s.e.m.) after 15 min. GHRH (50 μg i.v.) induced a GH peak of 9·7 ± 2·2 μg/l at 15 min. The combined administration of GHRP-6 and GHRH strikingly potentiated canine GH release with a peak of 54 ± 9·0 μg/l (P <0·01). Pretreatment with the cholinergic agonist pyridostigmine (30 mg per os) increased GHRP-6-stimulated GH secretion (37·9 ± 10·1 μg/l P <0·05), while the muscarinic blocker atropine (100 μg i.v.) completely abolished (GH peak lower than 2 μg/l) the stimulatory action of GHRP-6. On the other hand, administration of the α-2 adrenergic agonist clonidine (4 pg/kg i.v.) increased basal plasma GH levels without affecting GH responses to GHRP-6. Finally, while the α-1 adrenergic agonist methoxamine (5 mg i.v.) did not significantly increase GH responses to GHRP-6, administration of the α-1 adrenoceptor antagonist prazosin (20 mg i.v.) reduced GHRP-6-induced GH secretion (area under curve, 206 ± 39 vs 557 ± 172, P <0·05).
In summary, the synergistic effect of the combined administration of maximal doses of GHRP-6 and GHRH suggests that these two peptides act through different mechanisms. The finding that cholinergic drugs were able to modulate the GH secretion elicited by GHRP-6 argues against the hypothesis that such a peptide acts by influencing hypothalamic somatostatin release and suggests that it acts directly at the pituitary level. Finally, the unexpected lack of effect of clonidine and the inhibitory effect of prazosin on GHRP-6-induced GH secretion suggests that the role of α-adrenergic pathways in GH secretion is more complex than previously thought.
Journal of Endocrinology (1993) 138, 211–218
Changes induced by cadmium administration on thyroxine deiodination and sulfhydryl groups in rat liver
Authors: Paier B. , Hagmüller K. , Noli M. I. , Pondal M. Gonzalez , Stiegler C. , Zaninovich A. A. 
Published: December 2008

ABSTRACT
The effects of cadmium on 5′-deiodination of thyroxine (T4) by rat liver and on the hepatic concentration of non-protein sulfhydryl groups (NPSH) were studied in Wistar rats of 200–250 g body weight. A group of ten rats was injected with cadmium chloride (300 μg/100 g body weight i.p.) daily for 4 days. Another group of six rats received, in addition, dithiothreitol (DTT; 1 mg/100 g body weight i.p.) daily for the same period. A group of eight normal untreated rats served as control. T4 deiodination was also determined in aliquots of liver from untreated rats, with cadmium (2 or 5 mmol/l) and with or without DTT (0, 2·5, 5 or 10 mmol/l) plus 1 μCi 125I-labelled T4. Hepatic NPSH were measured by a colorimetric method employing dithioldinitrobenzoic acid. Homogenates were incubated for 90 min at 37 °C and chromatographed in a tertiary amyl alcohol: hexane: ammonia (2 mol/l) (10: 1: 12) system. Cadmium-injected rats showed a significant (P <0·01) decrease in T4 deiodination and in the generation of 125I (P <0·01) and tri-iodothyronine (T3) (P <0·02). NPSH were also decreased (P <0·02). Administration of DTT restored T4 deiodination and NPSH to normal. In-vitro addition of cadmium or DTT to normal rat liver homogenates induced similar effects on the degradation of T4. Serum concentrations of T4 (P <0·01) and T3 (P <0·01) declined significantly in cadmium-injected rats, whereas DTT administration failed to normalize serum hormone levels. The data suggest that cadmium may have decreased 5′-deiodinating activity through binding to sulfhydryl groups of 5′-deiodinase as it does in other enzymes. The effects on serum T4 concentrations may be unrelated to those on 5′-deiodinase.
Journal of Endocrinology (1993) 138, 219–224
Growth hormone receptor regulation in growth hormone-deficient dwarf rats
Authors: Carmignac D. F. , Robinson I. C. A. F. , Enberg B. , Norstedt G. 
Published: December 2008

ABSTRACT
In the rat, many actions of GH depend upon the sexually dimorphic pattern of exposure to GH. Hepatic human GH (hGH) receptor binding differs between the sexes and is sensitive to GH deficiency, but this has mostly been studied in acutely hypophysectomized rats, which lack all pituitary hormones. We have used a strain of GH-deficient dwarf (Dw) rats to determine whether chronic GH deficiency alters the normal developmental pattern and sexually dimorphic expression of hepatic GH receptors. Adult female Dw rats had lower levels of 125I-labelled hGH binding (reflecting predominantly lactogenic receptors) than their normal counterparts whereas there was no difference between adult Dw and normal males; binding capacity increased from 25 days of age, becoming sexually dimorphic from 40 days to adulthood in both strains (% specific binding/mg protein: normal males 1·6 ± 0·3, normal females 13·2 ± 1·1, Dw males 2·1 ±0·4, Dw females 10·0 ± 0·6). In contrast, hepatic 125I-labelled bovine GH (bGH) binding (somatogenic receptors) was much lower, and similar in both Dw and normal animals. A sex difference in 125I-labelled bGH binding was only seen in adult animals, and was considerably less marked in Dw rats compared with normal animals (normal males 1·3 ±0·1, normal females 2·5 ± 0·2, Dw males 1·9 ± 0·2, Dw females 2·4 ± 0·2%/mg protein). Continuous hGH infusion stimulated growth in female Dw rats, and raised somatogenic and lactogenic GH binding (3·2 ± 0·4 and 19·6 ± 2·5%/mg protein) compared with sham-infused controls (2·4 ± 0·2 and 7·9 ± 0·6%/mg protein). Dw rats had significantly smaller amounts of hepatic GH receptor mRNA than normal rats, but there was no significant sex difference in GH receptor mRNA levels in the dwarfs. The pituitary GH deficiency in Dw rats was present at birth and the relative deficit remained constant despite large increases in pituitary GH that occurred from birth to maturity. Thus whilst hepatic GH receptor expression can be altered by GH in Dw rats, their chronic GH deficiency causing severe dwarfism is accompanied by only small differences in hepatic GH receptor expression.
Journal of Endocrinology (1993) 138, 267–274
Expression of mRNA coding for pituitary hormones and pituitary-specific transcription factor in the pituitary gland of the rdw rat with hereditary dwarfism
Authors: Shibayama K. , Ohyama Y. , Ono M. , Furudate S. 
Published: December 2008

ABSTRACT
The rdw rat (gene symbol: rdw) with hereditary dwarfism has been shown immunohistochemically to have subnormal numbers not only of GH- but also of prolactin- and thyrotrophin-positive cells. To characterize the dwarfism of this strain, the expression of pituitary hormone mRNAs was examined by Northern hybridization. The pituitary gland in the rdw rat expressed 30–100 times less GH and prolactin mRNAs than normal controls, whereas mRNAs for pro-opiomelanocortin and the α subunit of rat glycoprotein hormone revealed a significant increase. There was a non-significant difference in rat LH-β subunit and FSH-β subunit between normal and rdw rats. The suppressed expression of a pituitary-specific transcription factor, Pit-1, is considered to cause hereditary dwarfism in mouse strains Snell and Jackson, whose phenotypes resemble those of the rdw rat. In this study, however, no difference in mRNA expression for Pit-1 was found between rdw rats and controls. This work indicates that the rdw rat may not have the same genotype as the phenotypically similar dwarf mice, Snell, Jackson and Ames.
Journal of Endocrinology (1993) 138, 307–313
Variability in the urinary excretion of growth hormone in children: a comparison with other urinary proteins
Authors: Skinner A. M. , Clayton P. E. , Price D. A. , Addison G. M. , Mui C. Y. W. 
Published: December 2008

ABSTRACT
As a basis for assessment of the clinical validity of urinary GH (uGH) measurements in children, the day-to-day variability in renal handling of GH has been compared with that of albumin, N-acetylglucosaminidase (NAG) and creatinine. Five overnight urine specimens were collected over a 2-week period from 78 healthy children (aged 5–16 years), 20 of normal stature and 58 with growth disorders; ten children were classified as GH-deficient (GHD) and 48 were designated short normal (SN).
The variability of excretion of each substance was expressed as a coefficient of variation (C.V.) which was not influenced by expressing the urine results as total mass excreted, concentration, excretion rate or as a ratio to creatinine. There was considerable night-to-night variability in the excretion of all substances (mean C.V. values for all groups: 56% for albumin, 41% for GH, 33% for NAG and 27% for creatinine). No differences were found in the variability of GH excretion between males and females, nor between prepubertal and pubertal subjects. The mean C.V. for uGH excretion ranged from 37% in normal and 35% in SN children to 52% in those with GHD (P <0·05). Assay variation rather than a change in renal protein handling accounted for the large variations in uGH concentrations of <5 pg/ml, thus contributing to the high uGH C.V. of the GHD group. Increasing the number of samples collected (up to five) decreased the expected sample variation (error) for uGH but not significantly and only improved efficiency in the diagnosis of growth disorders from 91 to 95%, while reducing the convenience and practicality of the test.
These results indicate that variation in urinary protein excretion over a 2-week period is considerable (albumin>GH>NAG) in both normal children and those with growth disorders. To apply this test to routine clinical management, we recommend comparison of a single overnight uGH measurement with normal ranges derived from age-, sex- and pubertal status-matched children.
Journal of Endocrinology (1993) 138, 337–343