bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vivo and in vitro effect of 1,25-dihydroxyvitamin D3 and 1,25-dihydroxy-16-ene-23-yne-vitamin D3 on the proliferation and differentiation of avian chondrocytes: their role in tibial dyschondroplasia
Authors: Farquharson C , Rennie J S , Loveridge N , Whitehead C C 
Published: December 2004

Abstract
1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) is regarded as the most biologically active metabolite of cholecalciferol. It prevents tibial dyschondroplasia (TD) in chicks where inhibition of chondrocyte differentiation within the growth plate occurs. However, it is unclear whether its mode of action is through direct interaction with its chondrocyte receptor and its known regulatory role in cell differentiation or is mediated by increased calcium absorption and mobilisation. Synthetic analogues of 1,25(OH)2D3 such as 1,25-dihydroxy-16-ene-23-yne cholecalciferol (RO 23–7553) with increased differentiation properties but reduced calcaemic activity have been synthesised. In this study, the in vitro and in vivo effects of 1,25(OH)2D3 and RO 23–7553 on chick chondrocyte growth and differentiation were examined. In addition, the in vivo effectiveness of these steroids in preventing TD in chicks was assessed. 1,25(OH)2D3 and RO 23–7553 (10−12-10−7 m) displayed biphasic concentration effects and had similar potencies in vitro in regulating chondrocyte proliferation and differentiation. However, while the incidence of TD in birds dosed with 1,25(OH)2D3 was lower (10%) than in control chicks (55%), RO 23–7553 was ineffective (50%). This may be the result of its reduced affinity (1000 times less) for the plasma vitamin D binding protein (DBP) and the chondrocyte receptor in comparison to that of 1,25(OH)2D3. A reduction in calcium supply to the chondrocyte may also result in decreased chondrocyte differentiation but blood ionised and plasma total calcium were normal in birds dosed with RO 23–7553. These data suggest that RO 23–7553 and 1,25(OH)2D3 regulate chondrocyte proliferation and differentiation similarly in vitro but not in vivo. This may be caused by differences in DBP binding and clearance rates of the two steroids in vivo.
Journal of Endocrinology (1996) 148, 465–474
The integrative control of adrenocorticotrophin secretion: a critical role for corticotrophin-releasing hormone
Authors: Evans M J , Mulligan R S , Livesey J H , Donald R A 
Published: December 2004

Abstract
Perifused equine anterior pituitary cells were used to investigate the relationships between the secretion of ACTH and substances known to either stimulate (corticotrophin-releasing hormone (CRH), and arginine vasopressin (AVP)) or inhibit (cortisol) ACTH secretion. The experiments were designed to mimic the hormone milieu present in vivo in the horse, with cortisol (0 or 100 nmol/l) and CRH (0 or 0·02 nmol/l) perifused continuously, and pulses of AVP (10 nmol/l) applied for 5 min at 30-min intervals.
In columns perifused with 0·02 nmol CRH/1 there was no significant overall effect of 100 nmol cortisol/l on the ACTH responses to pulses of AVP, although there was a significant interaction between AVP pulse number and cortisol showing that ACTH total area (pmol ACTH proportional to area under response curve) in response to AVP pulses 1 and 2 was significantly (P<0·05) decreased in columns perifused with 100 nmol cortisol/l. However ACTH incremental area (pmol ACTH proportional to the area above the CRH-induced baseline) was not affected by cortisol at any AVP pulse.
This contrasts with the effect of cortisol in columns perifused with 0 nmol CRH/l, where 100 nmol cortisol/l significantly decreased ACTH total area (P=0·0075) and incremental area (P=0·049) at all AVP pulses compared with the responses in columns receiving 0 nmol cortisol/l.
There was a fall off in ACTH responsiveness with time during the experiment which, in the presence of 0·02 nmol CRH/1, was significantly (P<0·001) greater with 0 nmol cortisol/l than with 100 nmol cortisol/l and if 6 (rather than 3) pulses of AVP were given, whereas with 0 nmol CRH/l there was no difference in the fall off with time between columns receiving 0 and 100 nmol cortisol/l.
These results show that the control of ACTH secretion is influenced not only by independent action of secretagogues such as CRH and AVP, or inhibitors such as cortisol, but by a complex interaction of these factors with one another. CRH may have a role in 'protecting' the ACTH response to pulses of AVP in the presence of cortisol. It follows that, in vivo, 'background' CRH could allow an increase in ACTH in response to AVP released by a new stress, despite the presence of elevated cortisol.
Journal of Endocrinology (1996) 148, 475–483
Expression of the c-myc gene in human adrenals: regulation by adrenocorticotropin in primary cultures
Authors: Liu J , Voutilainen R , Kahri A I , Heikkilä P 
Published: December 2004

Abstract
We have analyzed the expression of the c-myc proto-oncogene in human adrenal glands in vivo and in primary cell cultures by Northern blot analysis. c-myc mRNA was consistently expressed in all human adrenals studied. Expression in adult adrenals was found to be approximately 50% of that in fetal adrenals, but much higher than that in adult liver and kidney. Adrenocorticotropin (ACTH) treatment increased c-myc mRNA accumulation dose- and time-dependently up to more than 5-fold (on average), with the maximal effect at 2 h. (Bu)2cAMP and 12-O-tetradecanoyl phorbol 13-acetate (TPA) also induced c-myc gene expression. There was no synergistic effect between the ACTH, (Bu)2cAMP and TPA treatments. The basal level of c-myc expression was reduced by the protein kinase inhibitors H-7 (1-(5-isoquinolinesulfonyl)-2-methyl-piperazine dihydrochloride), staurosporine and HA1004 (N-(2-guanidinoethyl)-5-isoquinolinesulfonamide hydrochloride). H-7 totally abolished ACTH-, TPA- and (Bu)2cAMP-induced c-myc expression, while staurosporine inhibited the stimulatory effects of ACTH and TPA, and HA1004 weakly inhibited the effects of ACTH and (Bu)2cAMP. Incubation with cycloheximide or 10% fetal calf serum increased c-myc mRNA levels 3- and 4-fold respectively. Our data show that the c-myc gene is expressed abundantly in normal human adrenals, and that this expression can be regulated by multiple factors in the primary cultures.
Journal of Endocrinology (1996) 148, 523–529
Effects of pituitary adenylate cyclase-activating polypeptide and vasoactive intestinal polypeptide on cyclic AMP accumulation in sheep pituitary cells in vitro
Authors: Sawangjaroen K , Sernia C , Curlewis J D 
Published: December 2004

Abstract
Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) are known to stimulate adenylate cyclase activity in rat pituitary cells but no direct effects have been reported on sheep pituitary cells. In this study we determined whether either peptide could stimulate intracellular cAMP accumulation in dispersed sheep pituitary cells in primary culture. Time course studies with PACAP showed that tachyphylaxis developed rapidly and so a short incubation time (5 min) was used to define the dose–response relationship. PACAP dose-dependently stimulated intracellular cAMP levels with a half-maximum response at 2·9 ± 0·2 nmol/l (n=4). In contrast, VIP only caused a small increase in intracellular cAMP levels at the highest dose tested (1 μmol/l). The VIP antagonist [4C1-d-Phe6,Leu17]VIP had no effect on the cAMP response to either PACAP or VIP while the peptide PACAP(6–38), a putative PACAP antagonist, blocked the cAMP response to PACAP. The desensitisation to PACAP was further investigated by pretreating cells with PACAP for 30 min. After a further 15 min in culture medium alone, these cells showed no cAMP response to subsequent treatment with PACAP but could respond to forskolin. When a longer incubation period of 240 min was used between the first and second treatment with PACAP, a partial return in responsiveness to PACAP was observed. In summary, these results show that PACAP activates adenylate cyclase in sheep pituitary cells but that there is rapid development of tachyphylaxis. Experiments with the antagonists suggest that the response to PACAP is via the PACAP type I receptor. In contrast, physiological doses of VIP do not stimulate cAMP accumulation in sheep pituitary cells.
Journal of Endocrinology (1996) 148, 545–552
LH and testosterone modulate mercuric chloride-induced acute renal failure in male rats: the implication of stress-induced hypogonadism
Authors: Nomura K , Kikuchi C , Ogasawara M , Katayama M , Ujihara M , Toraya S , Demura H 
Published: December 2004

Abstract
The significance of stress-induced hypogonadism remains unclear. Since plasma testosterone and LH have renotropic activity that is other than reproductive, we hypothesize that stress-induced hypogonadism is an adaptive response to protect the kidney. To examine this hypothesis, we prepared hypogonadal male rats with different levels of LH and testosterone through orchiectomy (castration), through chronic treatment with a slowly secreted form of gonadotropin-releasing hormone agonist (GnRHA; GnRHA pretreatment), or through both treatments concomitantly (castration with GnRHA pretreatment). Castrated rats had undetectable plasma testosterone and high plasma LH. GnRHA-pretreated rats had low plasma testosterone and normal plasma LH. Castrated rats with GnRHA pretreatment had undetectable plasma testosterone and normal plasma LH. We compared their sensitivity to HgCl2 nephrotoxicity and found that, when a low dose of HgCl2 (1·5 mg/kg body weight (BW)) was injected s.c. to induce acute renal failure, endogenous creatinine clearance (Ccr) decreased from 390 ± 30 to 94 ± 17 ml/h per kg BW in intact (unpretreated) rats. Such a decrease in Ccr was completely prevented in castrated rats (388 ± 30 ml/h per kg BW) and partially prevented in GnRHA-pretreated rats (216 ± 40 ml/h per kg BW). When a high dose of HgCl2 (2·25 mg/kg BW) was injected, half of the eight intact rats died but castrated rats and GnRHA-pretreated rats survived (P<0·05). The elevated resistance in castrated rats was reduced when plasma LH was reduced with GnRHA pretreatment, but was restored by additional pretreatment with ovine LH (40 μg/day), as evidenced by changes in Ccr. Elevated resistance in castrated rats was also reduced by the administration of testosterone propionate. In conclusion, hypogonadism activated the preventive and defensive mechanisms that protect the kidney through both decreased plasma testosterone and high or even normal plasma LH.
Journal of Endocrinology (1996) 148, 553–559
Median charge of gonadotrophin isoforms in the pituitary gland and in the circulation of sheep fetuses from mid- to late gestation
Authors: Phillips D J , McNatty K P , Smith P , Pettersson K , Wide L 
Published: December 2004

Abstract
The heterogeneity of LH and FSH in the sheep fetus was studied by determining the median charge of pituitary and circulating isoforms. Pituitary extracts from male and female fetuses at days 75, 95, 120 and 135 of gestation were subjected to agarose suspension electrophoresis. For all fetuses except the day 75 age group, the median mobility of the gonadotrophin isoforms in matching serum samples from the individual fetuses were also determined. LH and FSH in extracts, peripheral samples and column eluates were measured using sensitive and specific sandwich fluoroimmunoassays for ovine gonadotrophins. The median charge of pituitary LH became more basic (P<0·001) with gestational age, whereas for pituitary FSH more acidic forms (P<0·001) were present in the older groups. The female fetuses had more basic pituitary isoforms of LH than the males (P<0·01) between days 95 and 135, and for FSH at day 75 (P<0·05). In the matching serum samples, the median charge of the LH (P<0·001) and FSH (P<0·05) isoforms were more acidic than those in the pituitary gland. No significant effects of age or sex were detected in the median charge of the gonadotrophin isoforms in serum, but in a number of instances the median charge could not be determined due to low serum concentrations which affected the group sizes. These data show that in the sheep fetus LH and FSH are differentially regulated in qualitative as well as quantitative terms, and that the charge of fetal gonadotrophin isoforms changes according to the age and sex of the fetus.
Journal of Endocrinology (1996) 149, 29–39
Acute effect of thyroid hormone in the rat heart: role of calcium
Authors: Segal J , Masalha S , Schwalb H , Merin G , Borman J B , Uretzky G 
Published: December 2004

Abstract
Several observations provide some clues as to the possible mode of the regulatory action of thyroid hormone (TH) in the heart, indicating delayed action at the level of the nucleus and acute effects on the plasma membrane. Here we present evidence for a direct and rapid stimulatory effect of TH in the intact normal heart. In the isolated perfused rat heart, 3,5,3′-tri-iodothyronine (T3) produced a positive inotropic effect increasing both the left ventricular peak systolic pressure (P) and +dP/dt values, but had no significant effect on heart rate. This effect of T3 was: (1) very rapid in onset (starting after 15 s) and transient, increasing gradually to reach a maximum (80% above control) at about 20 min, and declining progressively 20 to 30 min later; (2) dose-related and biphasic, occurring at physiological concentrations as low as 1 pm (+dP/dt) and 10 pm (P), reaching a maximum at 1 nm, and decreasing at higher concentrations; and (3) thyroid hormone specific, as shown by the effects of several TH analogs (l-T3>l-thyroxine (T4)=d-T3>d-T4; 3,3′,5′-tri-iodothyronine (rT3), 3,5,-l-di-iodothyronine and dl-thyronine had no effect). The calcium blockers nifedipine and verapamil, at concentrations of 10−8–10−5 m given before or after the addition of T3 (10−9–10−6 m), inhibited the T3-induced increase in cardiac inotropic activity in a time- and dose-related fashion. We suggest that the acute effect of TH in the heart is plasma membrane-mediated and calcium-dependent.
Journal of Endocrinology (1996) 149, 73–80
A V1-type receptor for mediating the neurohypophysial hormone-induced ACTH release in trout pituitary
Authors: Pierson P M , Guibbolini M E , Lahlou B 
Published: December 2004

Abstract
We analysed the effects of specific neurohypophysial analogues for pharmacological characterization of the type of vasotocin receptor involved in the control of the adrenocorticotrophin hormone (ACTH) release from the perifused pituitary in the rainbow trout, Oncorhynchus mykiss.
Mammalian corticotrophin releasing factor (CRF) and teleostean neurohypophysial peptides (arginine vasotocin (AVT) and isotocin (IT)) stimulated ACTH release. Analysis of concentrations giving half-maximal effects (D50) showed that these peptides affected ACTH release in the following order of potency: CRF (8 × 10−13m) >AVT (2 × 10−10 m)>IT (10−7 m). Maximal responses (Dmax) were obtained for hormonal concentrations of 10−10 m, 10−8 m and 10−6 m respectively. This suggests that AVT and IT have different roles in the control of ACTH release. The values obtained for AVT and IT were in agreement with the circulating levels we previously found for these peptides.
Specific V1 or V2 agonists or antagonists (with reference to vasopressin in mammals) were used to define the specificity of the neurohypophysial peptide receptor involved in this stimulation. The V1 agonist, [Phe2, Orn8]-oxytocin, stimulated ACTH release while the V2 agonist, [deamino1, Val4, d-Arg8]-vasopressin, had no such effect. Maximal and half-maximal responses were obtained in the presence of the V1 agonist with 10−7 m and 7 × 10−9 m respectively, and were in the range of values obtained with natural peptides. The V1 antagonist, [d(CH2)51, O-Me-Tyr2, Arg8]-vasopressin, and the V2 antagonist, [d(CH2)51, d-Ile2, Ile4, Arg8, Ala9]-vasopressin, maximally reversed the 10−9 m AVT-stimulated ACTH release by 60% and 25% respectively, for a 5 × 10−10 m concentration of the analogues and a D50 approximately 2 × 10−11 m.
These results demonstrated the presence of only one V1-type receptor in fish pituitary, with some of the structural and functional peculiarities typically displayed by the mammalian V1a-type receptor, but distinct from it. In this sense, the fish pituitary vasotocin receptor may represent a novel type of neurohypophysial hormone receptor, more closely related to the mammalian V1b-type.
Journal of Endocrinology (1996) 149, 109–115
Expression levels of the insulin-like growth factor-II gene (IGF2) in the human liver: developmental relationships of the four promoters
Authors: Li X , Cui H , Sandstedt B , Nordlinder H , Larsson E , Ekström T J 
Published: December 2004

Abstract
We have studied the insulin-like growth factor-II gene (IGF2) promoter usage in normal human liver from fetal to late adult life by quantifying the specific transcripts by RNase protection assays using exon-specific probes. While the fetal liver uses only three promoters (P2, P3, P4) for the transcription of IGF2, all four promoters can be used from the age of 2 months after birth.
The levels of the individual promoter transcripts vary substantially during development and the P3 promoter, which is a highly active fetal promoter, was not used by all the investigated adult patients but was detected in 30% of the adult group as a whole. The PI promoter, which has previously been considered as the only one responsible for IGF2 transcription in the postnatal/adult liver, displayed a trend of increasing relative and absolute activity throughout life, but in some adult cases it was found to be less active than the P4 promoter. The P4 promoter displayed an age-related trend of decreasing activity from a very high fetal level, but individual exceptions were apparent. The P2 promoter transcript, peaking at the age of 2 months, showed a relatively even absolute amount from 18 months onwards. Thus, while P2 and P3 were both found to reach their highest activity after birth, the P4 promoter displayed its highest transcription at the fetal stage.
The total IGF2 transcription, primarily from P2, P3 and P4, was found to peak shortly after birth. After this age, the P3 promoter transcript declined most rapidly and a low or zero amount was detected in adulthood. From the age of 18 months to old adulthood the total IGF2 mRNA, derived primarily from P1, P2 and P4, displayed a relatively even amount (approximately one tenth) of that seen at the peak at 2 months. This data may be important in relation to translatability of the various IGF2 transcripts.
Journal of Endocrinology (1996) 149, 117–124
Pulsatile and diurnal secretion of GH and IGF-I in the chronically catheterized pig fetus
Authors: Bauer M , Parvizi N 
Published: December 2004

Abstract
The ontogeny of GH and IGF-I secretion was investigated in the fetal pig. Pulse studies were performed to describe the pattern of GH release. Twenty-four-hour profiles were recorded to examine possible diurnal variations in these hormones.
(I) Pulse studies. Blood samples were obtained at 15-min intervals for 2-h periods from 24 male and 20 female fetuses at various gestational ages (fetal day 89–113; term 113 ± 1 s.d.). Fetuses revealed a pulsatile GH release. The GH pulse frequency did not vary with gestational age in either sex (0·95 ± 0·19 pulses/h). In males the GH pulse amplitude decreased with increasing fetal age (r= −0·41; P<0·02). In female fetuses no significant correlation could be calculated. Mean GH concentrations fell significantly in male fetuses 3 to 4 days before delivery (P<0·05) and the same tendency was observed in females (P<0·06). Between fetal days 94 and 98 GH pulse amplitude and GH and IGF-I concentrations were higher in males than in females (P<0·01, P<0·001 and P<0·02 respectively). Fetal IGF-I secretion showed no ontogenetic changes in both sexes. However, maternal IGF-I concentrations increased with progressing gestation (r=0·46; P<0·001).
(II) 24-h profiles. Eight male and four female late-gestational fetuses (fetal days 104–108) were studied. Blood samples were taken at 30-min intervals over 24 h. Dams and fetuses showed an episodic GH secretion over the 24-h period but no diurnal rhythm was observed. Whereas maternal IGF-I secretion was constant, fetal IGF-I release was characterized by marked fluctuations over the 24 h. In half of the fetuses (n=6) the fluctuations appeared at regular intervals. Again no diurnal rhythm existed.
These data demonstrated that: (1) porcine fetal GH secretion is pulsatile and decreases shortly before birth; (2) a sex difference in GH and IGF-I concentrations exists between fetal days 94 and 98, suggesting that IGF-I is at least partially under the control of GH before birth; (3) fetal GH and IGF-I secretion is episodic over 24 h, but does not vary diurnally; and (4) fetal and maternal GH and IGF-I secretion are regulated independently.
Journal of Endocrinology (1996) 149, 125–133
The effects of octreotide on GH receptor and IGF-I expression in the GH-deficient rat
Authors: Ambler G R , Butler A A , Padmanabhan J , Breier B H , Gluckman P D 
Published: December 2004

Abstract
Somatostatin has been suggested to influence the somatotrophic axis outside the central nervous system, in reducing GH-induced IGF-I mRNA and IGF-I generation. This study aimed to determine whether such effects were mediated via the GH receptor (GHR). GH-deficient dwarf rats aged 45–47 days (n=8 per group) received twice daily subcutaneous injections of octreotide (1 mg/kg) (group O), saline (group S), octreotide (1 mg/kg) plus bovine GH (0·25 mg/kg) (group OG), or bovine GH (0·25 mg/kg) plus saline (group G) for 10 days.
Octreotide-treated animals had less weight gain compared with saline-treated animals, but not when GH cotreated (group OG vs G). Octreotide had an overall effect on decreasing length gain (P<0·01). Serum IGF-I (ng/ml) was reduced by octreotide (group O 171 ±11, group S 239 ± 20, P<0·01; group OG 283 ± 30, group G 362 ± 10, P<0·001), as was serum insulin (P<0·001). A significant decrease in hepatic and muscle IGF-I mRNA expression was found as expected, yet this was not associated with decreased hepatic GHR expression. Rather, an increase in hepatic 125I-bovine GH specific binding was observed (P<0·001) and, in GH-cotreated animals (OG), hepatic GHR and GH binding protein (GHBP) mRNA expression were also increased by octreotide by approximately 40%. In muscle, octreotide was associated with an approximately 30% decrease in GHBP mRNA and no effect on GHR mRNA.
This study suggests that the suppressive effects of octreotide on IGF-I metabolism, at least in liver, are not mediated via down-regulation of GHR expression, but more likely by direct effects on IGF-I expression.
Journal of Endocrinology (1996) 149, 223–231