bluuebunny/crossref_metadata_2025_split huggingface dataset:
Constant low-dose oestradiol replacement accelerates skeletal maturation and growth in ovariectomized adolescent rhesus monkeys
Authors: Wilson M. E. , Gordon T. P. , Tanner J. M. 
Published: December 2008

ABSTRACT
The effects of oestradiol (OE2) on adolescent growth in female rhesus monkeys were evaluated by testing the hypothesis that, upon removal of the ovary, the increase in growth normally seen at the time of puberty would be abolished and that treatment with OE2 would restore it. Juvenile monkeys (n= 12) were ovariectomized and were given either an OE2-bearing silicone elastomer capsule implanted subcutaneously to simulate mid-pubertal concentrations ('treated = ', n = 8) or no steroid treatment ('control = ', n = 4). Females were studied from 18 to 42 months of age which, in intact females, typically encompasses the prepubertal period to the occurrence of first ovulation. Over the whole period, growth in body weight, crown–rump (CR) length and tibia length for control females were less than the 95% confidence limits of females treated with OE2. However, significant spurts of growth in both CR and tibia length occurred in the control as well as treated animals, although the peak velocities were somewhat lower for non-OE2-treated animals. Peak growth velocities occurred at an earlier chronological age in treated females, although at the same degree of skeletal maturity as found in control females. Skeletal maturity was significantly advanced in treated females from 27 months onward. Serum concentrations of nocturnal GH increased significantly with advancing age in both groups, with greater increases observed in treated females. Serum concentrations of IGF-I were higher in treated females until some 30 months of age, at which point concentrations increased in a similar fashion in both groups. IGF-I concentrations were elevated in the months preceding and following the peak CR growth velocity in treated females whereas concentrations of IGF-I rose coincidently with peak CR growth in control females. These data indicate that, in the absence of OE2, growth in female monkeys has periods of acceleration and that OE2 may enhance this pre-set pattern. Furthermore, the growth-promoting effects of OE2 are determined by the degree of skeletal maturity. Once a certain degree of skeletal maturity is attained, bones may be primed for maximal growth, but, as skeletal maturity continues to advance, the effect of OE2 on growth diminishes.
Journal of Endocrinology (1993) 137, 519–527
Endogenous opioid regulation of oxytocin release during parturition is reduced in ovariectomized rats
Authors: Way S. A. , Douglas A. J. , Dye S. , Bicknell R. J. , Leng G. , Russell J. A. 
Published: December 2008

ABSTRACT
Pregnant rats were ovariectomized (or shamovariectomized) on days 17, 18 or 21 of pregnancy and oestradiol-17β and progesterone were replaced. Prepartum oxytocin concentrations were significantly lower in ovariectomized steroid-treated rats than in intact controls, and on day 21 of pregnancy injection of relaxin into acutely ovariectomized rats significantly increased plasma oxytocin concentrations. During parturition, injection of the opioid antagonist naloxone induced significant increases in plasma oxytocin concentration compared with salineinjected rats. The naloxone-induced increase was significantly less in ovariectomized steroid-treated rats than in rats with intact ovaries, indicating that endogenous opioid activity is less in ovariectomized rats than in intact rats. The progress of parturition in the ovariectomized steroid-treated rats was severely disrupted compared with sham-ovariectomized rats despite similar plasma oxytocin levels at the birth of pup number 2; this disruption was not overcome by injection of naloxone or by the consequent increase in oxytocin secretion, indicating deficient preparation of the uterus and birth canal in the absence of relaxin. We conclude that the decreased oxytocin concentrations prepartum, the prolongation of parturition and the decrease in opioid tone in ovariectomized steroid-treated rats may be partly due to a lack of relaxin produced by the ovary.
Journal of Endocrinology (1993) 138, 13–22
pGlutamylglutamylprolineamide modulation of growth hormone secretion in domestic fowl: antagonism of thyrotrophin-releasing hormone action?
Authors: Harvey S. , Trudeau V. L. , Ashworth R. J. , Cockle S. M. 
Published: December 2008

ABSTRACT
Pyroglutamylglutamylprolineamide (pGlu-Glu-ProNH2) is a tripeptide with structural and immunological similarities to thyrotrophin-releasing hormone (TRH; pGlu-His-ProNH2). Since TRH stimulates GH secretion in domestic fowl, the possibility that pGlu-Glu-ProNH2 may also provoke GH release was investigated. Unlike TRH, pGlu-Glu-ProNH2 alone had no effect on GH release from incubated chicken pituitary glands and did not down-regulate pituitary TRH receptors. However, pGlu-Glu-ProNH2 suppressed TRH-induced GH release from pituitary glands incubated in vitro and competitively displaced [3H]methyl3-histidine2-TRH from pituitary membranes. Systemic injections of pGlu-Glu-ProNH2 had no significant effect on basal GH concentrations in conscious birds, but promptly lowered circulating GH levels in sodiumpentobarbitone anaesthetized fowl. Submaximal GH responses of conscious and anaesthetized birds to systemic TRH challenge were, however, potentiated by prior or concomitant administration of pGlu-Glu-ProNH2. These results demonstrate, for the first time, that pGlu-Glu-ProNH2 has biological activity, with inhibitory and stimulatory actions within the avian hypothalamo-pituitary axis. These results indicate that pGlu-Glu-ProNH2 may act as a TRH receptor antagonist within this axis.
Journal of Endocrinology (1993) 138, 137–147
Glucagon-like peptide-1(7–36)amide and glucose-dependent insulinotropic polypeptide secretion in response to nutrient ingestion in man: acute post-prandial and 24-h secretion patterns
Authors: Elliott R. M. , Morgan L. M. , Tredger J. A. , Deacon S. , Wright J. , Marks V. 
Published: December 2008

ABSTRACT
The acute effects of different macronutrients on the secretion of glucagon-like peptide-1(7–36)amide (GLP-1(7–36)amide) and glucose-dependent insulinotropic polypeptide (GIP) were compared in healthy human subjects. Circulating levels of the two hormones were measured over a 24-h period during which subjects consumed a mixed diet. In the first study, eight subjects consumed three equicaloric (375 kcal) test meals of carbohydrate, fat and protein. Small increases in plasma GLP-1(7–36) amide were found after all meals. Levels reached a maximum 30 min after the carbohydrate and 150 min after the fat load. Ingestion of both carbohydrate and fat induced substantial rises in GIP secretion, but the protein meal had no effect. In a second study, eight subjects consumed 75 g glucose or the equivalent portion of complex carbohydrate as boiled brown rice or barley. Plasma GIP, insulin and glucose levels increased after all three meals, the largest increase being observed following glucose and the smallest following the barley meal. Plasma GLP-1(7–36)amide levels rose only following the glucose meal. In the 24-h study, plasma GLP-1(7–36)amide and GIP concentrations were increased following every meal and remained elevated throughout the day, only falling to fasting levels at night. The increases in circulating GLP-1(7–36)amide and GIP levels following carbohydrate or a mixed meal are consistent with their role as incretins. The more sustained rises observed in the daytime during the 24-h study are consistent with an anabolic role in lipid metabolism.
Journal of Endocrinology (1993) 138, 159–166
Human recombinant inhibin A and testosterone act directly at the pituitary to suppress plasma concentrations of FSH in castrated rams
Authors: Tilbrook A. J. , de Kretser D. M. , Clarke I. J. 
Published: December 2008

ABSTRACT
The roles of inhibin and testosterone in the negative feedback control of the secretion of FSH were explored in experiments using castrated rams administered human recombinant inhibin A (hr-inhibin) and testosterone propionate (TP). Two experiments were conducted in the non-breeding season. In experiment 1, two groups of long-term castrated rams (wethers) were treated with an i.v. injection of either vehicle or hr-inhibin in two doses (25 and 50 μg) given 2 weeks apart. Plasma concentrations of FSH, measured by radioimmunoassay, were suppressed significantly (P<0·01) and equally by both doses of hr-inhibin with a mean (± s.e.m.) maximal suppression of FSH of 19·9 ± 2·60% occurring 6–10 h after injection. In experiment 2, hypothalamo-pituitary disconnected (HPD) wethers given 125 ng gonadotrophin-releasing hormone (GnRH) every 2 h, were treated with vehicle or 25 or 50 μg hr-inhibin before or after treatment (32 mg/day) with TP. A cross-over design was used so that each wether was treated with vehicle and hr-inhibin. Treatment with TP significantly (P<0·001) suppressed plasma concentrations of FSH by 56%. Both doses of hr-inhibin were similarly effective in significantly (P<0·05) suppressing plasma concentrations of FSH causing a mean suppression of 31·1 ± 5·60% 6–10 h after injection. The suppressive effect of hr-inhibin was significantly (P<0·05) increased when the wethers were treated with TP to a mean suppression of 50·7 ± 5·6% 6–10 h after injection. These data indicate that both inhibin and testosterone exert negative feedback control on FSH secretion in rams and that the suppressive effects of inhibin may be enhanced by testosterone. Furthermore, both inhibin and testosterone acted directly on the pituitary to suppress FSH secretion in rams. The inhibition of FSH by a direct pituitary action of testosterone in this study is at variance with our previous findings with HPD wethers during the breeding season when it was shown that testicular steroids have minimal feedback effects at this level. These discrepancies suggest that the sensitivity of the pituitary to negative feedback by testicular steroids may change with the breeding season independent of an input from the hypothalamus. Finally, the greater suppressive effects of hr-inhibin in HPD wethers in experiment 2 compared with the hypothalamo-pituitary intact wethers in experiment 1 suggests that the sensitivity of the pituitary to inhibin may be increased by limiting the GnRH stimulus to the pituitary.
Journal of Endocrinology (1993) 138, 181–189
Characterization of a novel non-peptide vasopressin V1 receptor antagonist (OPC-21268) in the rat
Authors: Burrell L. M. , Phillips P. A. , Stephenson J. , Risvanis J. , Hutchins A.-M. , Johnston C. I. 
Published: December 2008

ABSTRACT
A non-peptide, orally effective, vasopressin (AVP) V1 receptor antagonist 1-{1-[4-(3-acetylaminopropoxy) benzoyl]-4-piperidyl}-3,4-dihydro-2(1H)-quinolinone (OPC-21268) has recently been described. This paper reports the in-vitro and in-vivo characterization of OPC-21268 binding to vasopressin receptors in rat liver and kidney.
OPC-21268 caused a concentration-dependent displacement of the selective V1 receptor antagonist radioligand, 125I-labelled [d(CH2)5,sarcosine7]AVP to V1 receptors in both rat liver and kidney medulla membranes. The concentration of OPC-21268 that displaced 50% of specific AVP binding (IC50) was 40±3 nmol/l for liver V1 and 15±2 nmol/l for kidney V1 receptors (mean ± s.e.m.; n = 3). OPC-21268 had little effect on the selective V2 antagonist radioligand [3H]desGly-NH29[d(CH2)5,d-Ile2,Ile4] AVP binding to V2 receptors in renal medulla membranes (IC50 >0·1 mmol/l).
After oral administration to rats, OPC-21268 was an effective V1 antagonist in a time- and dose-dependent manner. Binding kinetic studies showed that OPC-21268 acted as a competitive antagonist at the liver V1 receptor in vitro and in vivo, in addition to its in-vitro competitive effects at the renal V1 receptor. OPC-21268 shows promise as an orally active V1 antagonist.
Journal of Endocrinology (1993) 138, 259–266
Plasma clearance and tissue distribution of labelled insulin-like growth factor-I (IGF-I) and an analogue LR3IGF-I in pregnant rats
Authors: Bastian S. E. P. , Walton P. E. , Wallace J. C. , Ballard F. J. 
Published: December 2008

ABSTRACT
To determine whether the changes in insulin-like growth factor-binding proteins (IGFBPs) and IGF-I levels during pregnancy in rats affect the clearance of IGFs from the circulation, we have measured pharmacokinetic parameters and the tissue distribution of radiolabelled IGF-I and LR3IGF-I, a potent analogue which has a markedly reduced affinity of binding to the IGFBPs. Intravenous boluses of radiolabelled growth factors were administered to catheterized virgin and age-matched pregnant rats on day 18 of gestation when plasma IGFBPs, in particular IGFBP-3, are dramatically reduced. IGF-I was cleared more rapidly from plasma in pregnant rats compared with the virgins; metabolic clearance rate (MCR) = 2·88±0·12 (s.e.m.) and 0·90±0·05 ml/min per kg respectively. Although LR3IGF-I was cleared more rapidly than IGF-I from plasma, similar clearance rates for the analogue were obtained in both pregnant and virgin animals, MCR = 9·19±0·15 and 9·84±0·28 ml/min per kg respectively. In virgin rat plasma, labelled IGF-I was mainly associated with the 150 kDa complex, whereas in pregnant rat plasma IGF-I was predominantly associated with lower Mr IGFBPs (approximately 30–50 kDa). The majority of LR3IGF-I was detected as free peptide. A larger proportion of the tracer was detected as small Mr breakdown products in plasma from rats under conditions of reduced binding to IGFBPs, e.g. during pregnancy or when LR3IGF-I was the labelled tracer, suggesting greater rates of IGF degradation. More LR3IGF-I tracer was detected in kidneys, ovaries and adrenals of virgin rats and in the ovaries and adrenals of pregnant rats, compared with IGF-I tracer. IGF-I radioactivity was greater than LR3IGF-I in caecum, brain, liver and heart in virgin rats and in kidneys, caecum, brain, liver, heart, placenta, fetus and fetal plasma of the pregnant rats. These results show that the reduction in IGFBP during pregnancy dramatically increased the clearance of IGF-I from the circulation towards that obtained with LR3IGF-I. The observation that less LR3IGF-I was detected in placenta, fetus and fetal plasma compared with IGF-I raises the possibility that the ability to bind IGFBPs during pregnancy may enhance IGF uptake by the conceptus.
Journal of Endocrinology (1993) 138, 327–336
The involvement of vasopressin in the renal actions of atrial natriuretic peptide in conscious fluid-balanced rats
Authors: Burgess W. J. , Balment R. J. 
Published: December 2008

ABSTRACT
The renal and endocrine actions of atrial natriuretic peptide (ANP) administered at a rate to induce plasma concentrations within the physiological range have been re-examined in conscious rats in which body fluid volume was maintained by infusion of replacement fluid at a rate to match spontaneous urine losses (servo-controlled replacement) throughout experimentation. The involvement of vasopressin in the actions of ANP was assessed by comparing the responses induced in Brattleboro (DI) and Long–Evans (LE) rats.
A rate of ANP administration inducing a less than twofold increment in circulating ANP concentration evoked a small but significant diuresis and natriuresis. In contrast to previous studies during which body fluid balance had not been maintained and the response to ANP was transient, renal responses were rapid in onset and sustained over the period of hormone administration. The change in renal excretion occurred without concomitant changes in mean arterial blood pressure, haematocrit or glomerular filtration rate, and without consistent alterations in the circulating concentrations of angiotensin II, vasopressin, aldosterone or corticosterone. Furthermore, although small differences between the two strains in the character of the response could be demonstrated, the evoked response was of similar magnitude in vasopressin-replete and -deficient animals.
In summary, in conscious rats in which body fluid volume was maintained, the profile of the diuretic and natriuretic responses evoked by low-rate ANP administration was different from that previously observed in anaesthetized and/or constantly infused preparations; being rapid in onset and sustained. The similarity in the renal effects observed following ANP administration in LE and DI rats in the present study suggests that vasopressin is not a prerequisite for the renal actions of ANP evoked by plasma concentrations within the physiological range.
Journal of Endocrinology (1993) 138, 413–420
Clearance of exogenous parathyroid hormone-related protein in pregnant, non-pregnant and fetal sheep, goats and pigs
Authors: Ratcliffe W. A. , Abbas S. K. , Care A. D. 
Published: December 2008

ABSTRACT
In the sheep, goat and pig, radiolabelled parathyroid hormone related protein (PTHRP) and immunoreactive PTHRP(1–34) and (1–86) were rapidly cleared from the circulation. Metabolic clearance rates (MCR) were in the range of 1·25–7·5 ml/min per kg and were slightly slower than that of intact PTH in man (10 ml/min per kg); while the mean MCR of labelled PTHRP(1–86) in fetal sheep and goats was significantly faster than that in their respective mothers (14·4 vs 4·0 ml/min per kg respectively). This may reflect increased metabolism of PTHRP by fetal tissues, e.g. the placenta. Similar rates of clearance of radiolabelled PTHRP(1–141), (1–86) and (1–34) suggest that clearance involves the amino terminus of the molecule.
Journal of Endocrinology (1993) 138, 459–465
Protein kinase in rat adipocytes: influence of androgenic status and regional fat distribution
Authors: Lacasa D. , Agli B. , Mur B. , Dieudonné M. N. , Giudicelli Y. 
Published: December 2008

ABSTRACT
The effects of castration and testosterone treatment on insulin- and phorbol ester (TPA)-stimulated lipogenic responses, phorbol dibutyrate-specific binding to protein kinase C (PKC) in the cytosol and the β-PKC isoform level quantified by immunoblotting were compared in rat fat cells from femoral subcutaneous (SC) and deep intra-abdominal (epididymal) fat deposits.
In control rats, the PKC content was lower in SC than in epididymal fat cells. After castration, the difference in PKC content between SC and epididymal fat cells was reduced and restored by testosterone treatment. However, androgenic status failed to modify the PKC content in SC fat cells. The lipogenic response to insulin was also differently regulated by the androgenic status in the two fat deposits. After castration, the response was increased in SC fat cells, while it was blunted in epididymal fat cells. These effects were corrected by testosterone administration.
These results demonstrate that, in white adipocytes, PKC is an additional biological parameter which varies according to the anatomical origin of the fat cells. They also provide evidence that PKC is controlled by androgens in vivo and emphasize the regional site specificity of such a control.
Journal of Endocrinology (1993) 138, 493–501
The effect of tri-iodothyronine on the membrane potential and intracellular sodium and potassium activities of rat soleus and extensor digitorum longus muscles
Authors: MacDermott M. 
Published: December 2008

ABSTRACT
Tri-iodothyronine (T3) induces a considerable increase in the number of Na/K pump units in rat skeletal muscles, but this effect is more pronounced in red muscles, such as soleus, than in white muscles such as extensor digitorum longus (EDL). In the present study, the effect of T3 on the membrane potential (Em) and the intracellular activities of K+ and Na+ (aKi and aNai) in the two muscle types has been studied using microelectrodes. Hyperthyroidism was induced by seven subcutaneous injections of 50 μg T3 per 100 g body weight on alternate days. Following treatment of rats with T3, the mean T3 concentration in the serum was 8·4 ± 0·46 nmol/l (s.d.) compared with 1·1 ± 0·16 nmol/l in the serum of untreated control rats, and the heart weight/body weight ratio of the treated rats had increased from 0·29 ± 0·01 in control rats to 0·39 ± 0·02. In soleus muscle fibres from the T3-treated rats, the Em, aKi and aNai were unchanged, whereas, in EDL muscle fibres from these rats, the Em had depolarized by 2 mV (P<0·01) and aNai had increased by 2 mmol/l (P<0·05). Since T3 induces not only an increase in the number of pump units and active movement of Na+ and K+ but also an increase in the passive fluxes of these ions, the results are discussed in terms of these two opposing ionic movements.
Journal of Endocrinology (1993) 138, 503–507
Concentration-dependent effects of adrenaline on the profile of insulin secretion from isolated human islets of Langerhans
Authors: Lacey R. J. , Cable H. C. , James R. F. L. , London N. J. M. , Scarpello J. H. B. , Morgan N. G. 
Published: December 2008

ABSTRACT
The effects of the mixed α/β-agonist adrenaline on insulin secretion from isolated human islets of Langerhans were studied. In static incubation experiments, adrenaline (0·1 nmol/l to 10 μmol/l) caused a concentration-dependent inhibition of glucose-induced insulin secretion from isolated human islets. However, perifusion experiments revealed that the time-course of the secretory changes induced by adrenaline was complex. When employed at a high concentration (1 μmol/l), adrenaline caused a sustained inhibition of glucose-induced insulin secretion, which could be relieved by the addition of the α2-antagonist yohimbine (10 μmol/l). By contrast, infusion of adrenaline at a lower concentration (10 nmol/l), produced a large initial potentiation of glucose-induced insulin secretion. This response was, however, short-lived and followed by sustained inhibition of secretion, which could be relieved by yohimbine (10 μmol/l). The initial stimulation of insulin secretion provoked by 10 nmol adrenaline/l was abolished when islets were incubated in the presence of the β-antagonist, propranolol (1 μmol/l), consistent with activation of β-adrenoceptors. In support of this, treatment of human islets with the selective β2-agonist clenbuterol, was also associated with marked stimulation of insulin secretion. By contrast, each of two selective β3-agonists tested failed to alter insulin secretion from human islets. The results indicate that human pancreatic B-cells are equipped with both α2-and β2-adrenoceptors which can affect insulin secretion. Adrenaline interacts with both of these but the α2-response is predominant and can overcome the tendency of β2-adrenoceptors to potentiate insulin release.
Journal of Endocrinology (1993) 138, 555–563